Effects of hyperglycemia on rat cavernous nerve axons: a functional and ultrastructural study.

PubMed

Zotova, Elena G; Schaumburg, Herbert H; Raine, Cedric S; Cannella, Barbara; Tar, Moses; Melman, Arnold; Arezzo, Joseph C

2008-10-01

The present study explored parallel changes in the physiology and structure of myelinated (Adelta) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocin-induced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (< 2.5 m/s). Even with prolonged hyperglycemia (> 4 months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy.

EFFECTS OF HYPERGLYCEMIA ON RAT CAVERNOUS NERVE AXONS: A FUNCTIONAL AND ULTRASTRUCTURAL STUDY

PubMed Central

Zotova, Elena G.; Schaumburg, Herbert H.; Raine, Cedric S.; Cannella, Barbara; Tar, Moses; Melman, Arnold; Arezzo, Joseph C.

2008-01-01

The present study explored parallel changes in the physiology and structure of myelinated (Aδ) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocin-induced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (<2.5 m/sec). Even with prolonged hyperglycemia (> 4 months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy. PMID:18687329

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

ERIC Educational Resources Information Center

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

2014-01-01

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

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

PubMed Central

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

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

PubMed

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.

Neuropathy-induced spinal GAP-43 expression is not a main player in the onset of mechanical pain hypersensitivity.

PubMed

Jaken, Robby J; van Gorp, Sebastiaan; Joosten, Elbert A; Losen, Mario; Martínez-Martínez, Pilar; De Baets, Marc; Marcus, Marco A; Deumens, Ronald

2011-12-01

Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. Spinal GAP-43 was found to be upregulated in the superficial L5 dorsal horn from 5 up to 10 days after injury. GAP-43 was co-localized with calcitonin-gene related peptide (CGRP), but not vesicular glutamate transporter-1 (VGLUT-1), IB4, or protein kinase-γ (PKC-γ), suggesting the regulation of GAP-43 in peptidergic nociceptive afferents. These GAP-43/CGRP fibers may be indicative of sprouting peptidergic fibers. Fiber sprouting largely depends on growth factors, which are typically associated with neuro-inflammatory processes. The putative role of neuropathy-induced GAP-43 expression in the development of mechanical pain hypersensitivity was investigated using the immune modulator propentofylline. Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity.

Laser beam coupling into nerve fiber myelin allows one to assess its structural membrane properties

NASA Astrophysics Data System (ADS)

Kutuzov, Nikolay P.; Brazhe, Alexey R.; Lyaskovskiy, Vladimir L.; Maksimov, Georgy V.

2015-05-01

We show that myelin, the insulation wrap of nerve fibers, can couple laser light, thus behaving as a single-cell optical device. The effect was employed to map distinct myelin regions based on the coupling efficiency. Raman spectra acquisition allowed us to simultaneously understand the underlying microscopic differences in the membrane lipid ordering degree. The described method potentially provides new capabilities in myelin-associated disease studies and can be used as a handy tool for myelin structure investigation in combination with other methods.

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

PubMed

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

2013-05-01

To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). Prospective cross-sectional study. Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. Copyright © 2013 Elsevier Inc. All rights reserved.

Peripheral choline acetyltransferase in rat skin demonstrated by immunohistochemistry.

PubMed

Hanada, Keiji; Kishimoto, Saburo; Bellier, Jean-Pierre; Kimura, Hiroshi

2013-03-01

Conventional choline acetyltransferase immunohistochemistry has been used widely for visualizing central cholinergic neurons and fibers but not often for labeling peripheral structures, probably because of their poor staining. The recent identification of the peripheral type of choline acetyltransferase (pChAT) has enabled the clear immunohistochemical detection of many known peripheral cholinergic elements. Here, we report the presence of pChAT-immunoreactive nerve fibers in rat skin. Intensely stained nerve fibers were distributed in association with eccrine sweat glands, blood vessels, hair follicles and portions just beneath the epidermis. These results suggest that pChAT-positive nerves participate in the sympathetic cholinergic innervation of eccrine sweat glands. Moreover, pChAT also appears to play a role in cutaneous sensory nerve endings. These findings are supported by the presence of many pChAT-positive neuronal cells in the sympathetic ganglion and dorsal root ganglion. Thus, pChAT immunohistochemistry should provide a novel and unique tool for studying cholinergic nerves in the skin.

Optical coherence tomography platforms and parameters for glaucoma diagnosis and progression.

PubMed

Mwanza, Jean-Claude; Budenz, Donald L

2016-03-01

Optical coherence tomography (OCT) aids in the diagnosis and long-term monitoring of various ocular diseases, including glaucoma. Initially, the retinal nerve fiber layer was the only OCT structural parameter used in glaucoma. Subsequent research has resulted in more retinal and optic nerve head parameters. In addition, OCT is being investigated for its ability to assess ocular hemodynamics. This review summarizes these spectral domain-optical coherence tomography (SDOCT) parameters in the context of glaucoma. Several new SDOCT retinal nerve fiber layer, optic nerve head, and macular parameters with good glaucoma diagnostic ability have been added to existing ones recently. The combination of SDOCT and Doppler or angiography has also resulted in hemodynamic parameters that may prove to be useful in the functional assessment in glaucoma. OCT technology is advancing not only as a tool for structural assessment, but also as a multimodality tool to assess both structure and function to enhance our understanding of glaucoma, and ultimately clinical decisions.

Palisade endings are present in canine extraocular muscles and have a cholinergic phenotype.

PubMed

Rungaldier, Stefanie; Pomikal, Christine; Streicher, Johannes; Blumer, Roland

2009-11-20

Classical proprioceptors, like Golgi tendon organs and muscle spindles are absent in the extraocular muscles (EOMs) of most mammals. Instead, a nerve end organ was detected in the EOMs of each species including sheep, cat, rabbit, rat, monkey, and human examined so far: the palisade ending. Until now no clear evidence appeared that palisade endings are also present in canine EOMs. Here, we analyzed dog EOMs by confocal laser scanning microscopy, 3D reconstruction, and transmission electron microscopy. In EOM wholemount preparations stained with antibodies against neurofilament and synaptophysin we could demonstrate typical palisade endings. Nerve fibers coming from the muscle extend into the tendon. There, the nerve fibers turn 180 degrees and return to branch into preterminal axons which establish nerve terminals around a single muscle fiber tip. Fine structural analysis revealed that each palisade ending in dog EOMs establish nerve terminals on the tendon. In some palisade endings we found nerve terminals contacting the muscle fiber as well. Such neuromuscular contacts have a basal lamina in the synaptic cleft. By using an antibody against choline acetyltransferase (ChAT) we proved that canine palisade endings are ChAT-immunoreactive. This study shows that palisade endings are present in canine EOMs. In line with prior findings in cat and monkey, palisade endings in dog have a cholinergic phenotype.

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

PubMed Central

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

[Morphologic studies of the protective role of catechin on kanamycin otoneurotoxicity in SD rats].

PubMed

Liu, Guo-hui; Xie, Ding-hua; Wu, Wei-jing

2002-12-28

To determine the protection of catechin on aminoglycoside antibiotics otoneurotoxicity in SD rats, and observe the morphologic changes of cochlear efferent nerve terminals and outer hair cells after the injection of kanamycin and the feeding of catechin by the stomach tube. Thirty-eight SD rats were randomly assigned into three experimental groups (KM-treated, catechin-treated, KM and catechin in combination) and one control group. The KM-treated group was given kanamycin in a dose of 500 mg.(kg.d)-1 for 14 days. The catechin-treated group was given catechin once by the stomach tube in a dose of 400 mg.(kg.d)-1. Two kinds of medicine were simultaneously given in the KM+ catechin group. Transmission electron microscopy was utilized to observe the subcellular structure of efferent nerve fibers and outer hair cells. The densities of efferent nerve fibers and terminals were examined and the numbers of efferent nerve fibers and terminals were numerated by the surface preparation using modified histochemical staining for acetylcholinesterase (AchE). The damage in the group protected by catechin was relieved compared with the unprotected group. No damage was found in the catechin-treated alone group and controls. The densities and numbers of efferent nerve fibers and terminals were obviously fewer in the unprotected group than in the protected group and controls(P < 0.05). There was no significant difference in the numbers of efferent nerve fibers and terminals of the group protected by catechin compared with the controls and the catechin-treated group (P > 0.05). Catechin significantly protects MOC efferent nerves in kanamycin otoneurotoxicity.

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke.

PubMed

Khan, Adnan; Akhtar, Naveed; Kamran, Saadat; Ponirakis, Georgios; Petropoulos, Ioannis N; Tunio, Nahel A; Dargham, Soha R; Imam, Yahia; Sartaj, Faheem; Parray, Aijaz; Bourke, Paula; Khan, Rabia; Santos, Mark; Joseph, Sujatha; Shuaib, Ashfaq; Malik, Rayaz A

2017-11-01

Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance ( P <0.001, P <0.001, P <0.001), impaired glucose tolerance ( P =0.004, P <0.001, P =0.002), and type 2 diabetes mellitus ( P <0.001, P <0.001, P <0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density ( r =-0.187, P =0.03; r =-0.229 P =0.01), corneal nerve fiber length ( r =-0.228, P =0.009; r =-0.285; P =0.001), and corneal nerve branch density ( r =-0.187, P =0.033; r =-0.229, P =0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

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

PubMed

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.

Expression of Cocaine and Amphetamine Regulated Transcript (CART) in the Porcine Intramural Neurons of Stomach in the Course of Experimentally Induced Diabetes Mellitus.

PubMed

Bulc, Michał; Gonkowski, Sławomir; Całka, Jarosław

2015-11-01

In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility.

In vivo thickness and birefringence determination of the human retinal nerve fiber layer using polarization-sensitive optical coherence tomography.

PubMed

Cense, B; Chen, T C; de Boer, J F

2006-01-01

Thinning of the retinal nerve fiber layer and changes in retinal nerve fiber layer birefringence may both precede clinically detectable glaucomatous vision loss. We present in vivo thickness and depth-resolved birefringence measurements of the human retinal nerve fiber layer (RNFL) by use of polarization-sensitive optical coherence tomography (PS-OCT). Using a fiber-based PS-OCT setup real-time images of the human retina in vivo were recorded, co-registered with retinal video images of the location of PS-OCT scans. PS-OCT scans around the optic nerve head (ONH) of two healthy young volunteers were made using 10 concentric circles of increasing radius. Both the mean retinal nerve fiber layer thickness and mean retinal nerve fiber birefringence for each of 48 sectors on a circle were determined. The retinal nerve fiber layer thickness and birefringence varied as a function of sector around the ONH. Measured double pass phase retardation per unit depth values around the ONH range between 0.10 and 0.35 degrees/microm. The retinal nerve fiber layer becomes thinner with increasing distance from the ONH. In contrast, the birefringence does not vary significantly with increasing distance from the ONH.

Epithelial innervation of human cornea: a three-dimensional study using confocal laser scanning fluorescence microscopy.

PubMed

Guthoff, Rudolf F; Wienss, Holger; Hahnel, Christian; Wree, Andreas

2005-07-01

Evaluation of a new method to visualize distribution and morphology of human corneal nerves (Adelta- and C-fibers) by means of fluorescence staining, confocal laser scanning microscopy, and 3-dimensional (3D) reconstruction. Trephinates of corneas with a diagnosis of Fuchs corneal dystrophy were sliced into layers of 200 microm thickness using a Draeger microkeratome (Storz, Germany). The anterior lamella was stained with the Life/Dead-Kit (Molecular Probes Inc.), examined by the confocal laser scanning microscope "Odyssey XL," step size between 0.5 and 1 microm, and optical sections were digitally 3D-reconstructed. Immediate staining of explanted corneas by the Life/Dead-Kit gave a complete picture of the nerves in the central human cornea. Thin nerves running parallel to the Bowman layer in the subepithelial plexus perforate the Bowman layer orthogonally through tube-like structures. Passing the Bowman layer, Adelta- and C-fibers can be clearly distinguished by fiber diameter, and, while running in the basal epithelial plexus, by their spatial arrangement. Adelta-fibers run straight and parallel to the Bowman layer underneath the basal cell layer. C-fibers, after a short run parallel to the Bowman layer, send off multiple branches penetrating epithelial cell layers orthogonally, ending blindly in invaginations of the superficial cells. In contrast to C-fibers, Adelta-fibers show characteristic bulbous formations when kinking into the basal epithelial plexus. Ex-vivo fluorescence staining of the cornea and 3D reconstructions of confocal scans provide a fast and easily reproducible tool to visualize nerves of the anterior living cornea at high resolution. This may help to clarify gross variations of nerve fiber patterns under various clinical and experimental conditions.

Nerve Fiber Activation During Peripheral Nerve Field Stimulation: Importance of Electrode Orientation and Estimation of Area of Paresthesia.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-04-01

Low back pain is one of the indications for using peripheral nerve field stimulation (PNFS). However, the effect of PNFS varies between patients; several stimulation parameters have not been investigated in depth, such as orientation of the nerve fiber in relation to the electrode. While placing the electrode parallel to the nerve fiber may give lower activation thresholds, anodal blocking may occur when the propagating action potential passes an anode. A finite element model was used to simulate the extracellular potential during PNFS. This was combined with an active cable model of Aβ and Aδ nerve fibers. It was investigated how the angle between the nerve fiber and electrode affected the nerve activation and whether anodal blocking could occur. Finally, the area of paresthesia was estimated and compared with any concomitant Aδ fiber activation. The lowest threshold was found when nerve and electrode were in parallel, and that anodal blocking did not appear to occur during PNFS. The activation of Aβ fibers was within therapeutic range (<10V) of PNFS; however, within this range, Aδ fiber activation also may occur. The combined area of activated Aβ fibers (paresthesia) was at least two times larger than Aδ fibers for similar stimulation intensities. No evidence of anodal blocking was observed in this PNFS model. The thresholds were lowest when the nerves and electrodes were parallel; thus, it may be relevant to investigate the overall position of the target nerve fibers prior to electrode placement. © 2015 International Neuromodulation Society.

Morphology and Neurochemistry of Rabbit Iris Innervation

PubMed Central

He, Jiucheng; Bazan, Haydee E.P.

2016-01-01

The aim of this study was to map the entire nerve architecture and sensory neuropeptide content of the rabbit iris. Irises from New Zealand rabbits were stained with antibodies against neuronal-class βIII-tubulin, calcitonin gene-related peptide (CGRP) and substance P (SP), and whole-mount images were acquired to build a two-dimensional view of the iridal nerve architecture. After taking images in time-lapse mode, we observed thick nerves running in the iris stroma close to the anterior epithelia, forming four to five stromal nerve rings from the iris periphery to the pupillary margin and sub-branches that connected with each other, constituting the stromal nerve plexus. In the anterior side, fine divisions derivated from the stromal nerves, forming a nerve network-like structure to innervate the superficial anterior border layer, with the pupillary margin having the densest innervation. In the posterior side, the nerve bundles ran along with the pupil dilator muscle in a radial pattern. The morphology of the iris nerves on both sides changed with pupil size. To obtain the relative content of the neuropeptides in the iris, the specimens were double stained with βIII-tubulin and CGRP or SP antibodies. Relative nerve fiber densities for each fiber population were assessed quantitatively by computer-assisted analysis. On the anterior side, CGRP-positive nerve fibers constituted about 61%, while SP-positive nerves constitute about 30.5%, of the total nerve content, which was expressed as βIII tubulin-positive fibers. In addition, in the anterior stroma of the collarette region, there were non-neuronal cells that were positive for SP. On the posterior side, CGRP-positive nerve fibers were about 69% of total nerve content, while SP constituted only up to 20%. Similarly, in the trigeminal ganglia (TG), the number of CGRP-positive neurons significantly outnumbered those that were positive for SP. Also, all the SP-positive neurons were labeled with CGRP. This is the first study to provide a two-dimensional whole mount and a cross-sectional view of the entire iris nerve architecture. Considering the anatomical location, the high expression of CGRP and SP suggests that these neuropeptides may play a role in the pathogenesis of anterior uveitis, glaucoma, cataracts and chronic ocular pain. PMID:25752697

Morphology and neurochemistry of rabbit iris innervation.

PubMed

He, Jiucheng; Bazan, Haydee E P

2015-06-01

The aim of this study was to map the entire nerve architecture and sensory neuropeptide content of the rabbit iris. Irises from New Zealand rabbits were stained with antibodies against neuronal-class βIII-tubulin, calcitonin gene-related peptide (CGRP) and substance P (SP), and whole-mount images were acquired to build a two-dimensional view of the iridal nerve architecture. After taking images in time-lapse mode, we observed thick nerves running in the iris stroma close to the anterior epithelia, forming four to five stromal nerve rings from the iris periphery to the pupillary margin and sub-branches that connected with each other, constituting the stromal nerve plexus. In the anterior side, fine divisions derivated from the stromal nerves, forming a nerve network-like structure to innervate the superficial anterior border layer, with the pupillary margin having the densest innervation. In the posterior side, the nerve bundles ran along with the pupil dilator muscle in a radial pattern. The morphology of the iris nerves on both sides changed with pupil size. To obtain the relative content of the neuropeptides in the iris, the specimens were double stained with βIII-tubulin and CGRP or SP antibodies. Relative nerve fiber densities for each fiber population were assessed quantitatively by computer-assisted analysis. On the anterior side, CGRP-positive nerve fibers constituted about 61%, while SP-positive nerves constitute about 30.5%, of the total nerve content, which was expressed as βIII tubulin-positive fibers. In addition, in the anterior stroma of the collarette region, there were non-neuronal cells that were positive for SP. On the posterior side, CGRP-positive nerve fibers were about 69% of total nerve content, while SP constituted only up to 20%. Similarly, in the trigeminal ganglia (TG), the number of CGRP-positive neurons significantly outnumbered those that were positive for SP. Also, all the SP-positive neurons were labeled with CGRP. This is the first study to provide a two-dimensional whole mount and a cross-sectional view of the entire iris nerve architecture. Considering the anatomical location, the high expression of CGRP and SP suggests that these neuropeptides may play a role in the pathogenesis of anterior uveitis, glaucoma, cataracts and chronic ocular pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structured polarized light microscopy (SPLM) for mapping collagen fiber orientation of ocular tissues

NASA Astrophysics Data System (ADS)

Yang, Bin; Brazile, Bryn; Jan, Ning-Jiun; Voorhees, Andrew P.; Sigal, Ian A.

2018-02-01

Glaucoma is a disease characterized by progressive and irreversible vision loss leading to blindness. This vision loss is believed to be largely determined by the biomechanics of the optic nerve head region. Optic nerve head biomechanics, in turn, is determined by the properties of the constituent collagen. However, it is challenging to visualize and quantify collagen morphology and orientation in situ, and therefore often studies of the region collagen have used histological sections. Here we describe SPLM, a novel imaging technique that combines structured light illumination and polarized light microscopy (PLM) to enable collagen fiber visualization and fiber orientation mapping without requiring tissue sectioning. We developed a custom automated SPLM imaging system based on an upright microscope and a digital micromirror device (DMD) projector. The high spatial frequency patterns were used to achieve effective background suppression. Enhanced scattering sensitivity with SPLM resulted in images with highly improved visibility of collagen structures, even of tissues covered by pigment. SPLM produced improved fiber orientation maps from superficial layers compared to depth-averaged orientation from regular PLM. SPLM imaging provides valuable information of collagen fiber morphology and orientation in situ thus strengthening the study of ocular collagen fiber biomechanics and glaucoma.

Palisade endings are present in canine extraocular muscles and have a cholinergic phenotype

PubMed Central

RUNGALDIER, Stefanie; POMIKAL, Christine; STREICHER, Johannes; BLUMER, Roland

2016-01-01

Classical proprioceptors, like Golgi tendon organs and muscle spindles are absent in the extraocular muscles (EOMs) of most mammals. Instead, a nerve end organ was detected in the EOMs of each species including sheep, cats, rabbits, rats, monkeys, and man examined so far: the palisade ending. Until now no evidence appeared that palisade endings are present in canine EOMs. We analyzed dog EOMs by confocal laser scanning microscopy, 3D reconstruction, and transmission electron microscopy. In EOM wholemount preparations stained with antibodies against neurofilament and synaptophysin we found typical palisade endings. Nerve fibers coming from the muscle extended into the tendon. There, the nerve fibers turned 180° and returned to branch into preterminal axons which established nerve terminals around a single muscle fiber tip. Fine structural analyses revealed that each palisade ending in dog EOMs established nerve terminals on the tendon. In some palisade endings we found nerve terminals contacting the muscle fiber as well. Such neuromuscular contacts had a basal lamina in the synaptic cleft thereby resembling motor terminals. By using antibodies against choline acetyltransferase (ChAT) we proved that canine palisade endings are ChAT-immunoreactive. This study shows that palisade endings are present in canine EOMs. In line with prior findings in cat and monkey, palisade endings in dog have a cholinergic phenotype. PMID:19766165

An ultrastructural study of calcitonin gene-related peptide-immunoreactive nerve fibers innervating the rat posterior longitudinal ligament. A morphologic basis for their possible efferent actions.

PubMed

Imai, S; Konttinen, Y T; Tokunaga, Y; Maeda, T; Hukuda, S; Santavirta, S

1997-09-01

The present study investigated ultrastructural characteristics of calcitonin gene-related peptide-immunoreactive nerve fibers in the posterior longitudinal ligament of the rat lumbar spine. To provide a morphologic basis for assessment of the afferent and, in particular, efferent functions of calcitonin gene-related peptide immunoreactive nerves in the posterior longitudinal ligament and their eventual role in degenerative spondylarthropathies and low back pain. Previous studies using light-microscopic localization of sensory neuronal markers such as calcitonin gene-related peptide have reported the presence of sensory fibers in the supporting structures of the vertebral column. Meanwhile, accumulating research data have suggested efferent properties for calcitonin gene-related peptide, i.e., a trophic action that alters the intrinsic properties of target cells not through transient action of synaptic transmission, but through long-lasting signal transmission by the secreted neuropeptides. To verify such trophic, paracrine actions of the calcitonin gene-related peptide-containing fibers in the posterior longitudinal ligament, however, ultrastructural details of the terminals and their spatial relationship to their eventual target structures have to be elucidated. Rat posterior longitudinal ligaments were stained immunohistochemically for calcitonin gene-related peptide. Light-microscopic analysis of the semithin sections facilitated subsequent electron microscopy of specific sites of the posterior longitudinal ligament to determine ultrastructural details and nerve fiber-target relationships. The rat lumbar posterior longitudinal ligament was found to be innervated by two distinctive calcitonin gene-related peptide immunoreactive nerve networks. In immunoelectronmicroscopy, the fibers of the deep network had numerous free nerve endings, whereas those of the superficial network showed spatial associations with other non-calcitonin gene-related peptide immunoreactive components of the network. In both systems, naked axons not covered by the Schwann cells made close spatial contact with smooth muscle cells: of blood vessels and resident posterior longitudinal ligament fibroblasts. The ultrastructural characteristics of the innervation of the rat posterior longitudinal ligament would be compatible not only with a nociceptive function, but also with neuromodulatory, vasoregulatory, and trophic functions, as has already been established in some visceral organs.

Conversion of muscle fiber types in regenerating chicken muscles following cross-reinnervation.

PubMed

Kikuchi, T; Akiba, T; Ashmore, C R

1986-01-01

Slow-tonic anterior latissimus dorsi (ALD) and fast-twitch posterior latissimus dorsi (PLD) muscles of 7 to 10-day-old White Leghorn chickens were crushed and allowed to be reinnervated by their own nerve, or crushed and transplanted to the other side and allowed to be reinnervated by the nerve of the side to which they were transplanted. Following transplantation, changes in the weight of the muscle, fiber-type composition and innervation pattern during regeneration were investigated. Normal growth rate of PLD was about twice that of ALD. Regenerating PLD, however, atrophied rapidly after crushing and denervation whether innervated by its own nerve or the other nerve type, whereas ALD reinnervated by its own nerve showed marked hypertrophy. PLD fibers transformed rapidly to fast-twitch alpha or slow-tonic (ST) fibers when they were reinnervated by PLD or ALD nerve, respectively. When ALD fibers were reinnervated by their own nerve, they differentiated into ST fibers that were surrounded by smaller immature fibers. ALD fibers were, however, resistant to complete control by fast-twitch PLD nerve and contained a large number of slow fibers (ST and beta) long after transplantation. Slow fibers in regenerates were initially multiply innervated, but later transformed into fast-twitch alpha fibers that were focally innervated. The mode of differentiation and innervation pattern of different muscle fiber types in regenerating muscles are discussed.

Hierarchical models for epidermal nerve fiber data.

PubMed

Andersson, Claes; Rajala, Tuomas; Särkkä, Aila

2018-02-10

While epidermal nerve fiber (ENF) data have been used to study the effects of small fiber neuropathies through the density and the spatial patterns of the ENFs, little research has been focused on the effects on the individual nerve fibers. Studying the individual nerve fibers might give a better understanding of the effects of the neuropathy on the growth process of the individual ENFs. In this study, data from 32 healthy volunteers and 20 diabetic subjects, obtained from suction induced skin blister biopsies, are analyzed by comparing statistics for the nerve fibers as a whole and for the segments that a nerve fiber is composed of. Moreover, it is evaluated whether this type of data can be used to detect diabetic neuropathy, by using hierarchical models to perform unsupervised classification of the subjects. It is found that using the information about the individual nerve fibers in combination with the ENF counts yields a considerable improvement as compared to using the ENF counts only. Copyright © 2017 John Wiley & Sons, Ltd.

Morphological studies of the vestibular nerve

NASA Technical Reports Server (NTRS)

Bergstroem, B.

1973-01-01

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

The dimensions and characteristics of the subepidermal nerve plexus in human skin--terminal Schwann cells constitute a substantial cell population within the superficial dermis.

PubMed

Reinisch, Christina M; Tschachler, Erwin

2012-03-01

The skin constitutes the largest sensorial organ. Its nervous system consists of different types of afferent nerve fibers which spread out immediately beneath the skin surface to sense temperature, touch and pain. Our aim was to investigate the dimension and topographic relationship of the different nerve fibers of the subepidermal nerve plexus in human hairy skin and to analyze numbers and marker expression of terminal Schwann cells. Nerve fibers and Schwann cells were investigated on dermal sheet preparations and thick sections of skin from various body regions of 10 individuals. The dimension of subepidermal nerve fibers varied between different body sites with highest values in chest skin (100 ± 18 mm/mm(2)) and lowest in posterior forearm skin (53 ± 10 mm/mm(2)). The majority of fibers (85.79%) were unmyelinated, thus representing C-fibers, of which 7.84% were peptidergic. Neurofilament-positive fibers (A-fibers) accounted for 14.21% and fibers positive for both neurofilament and myelin (Aβ-fibers) for only 0.18%. The number of Schwann cells varied in accordance with nerve fiber length from 453 ± 108 on chest skin to 184 ± 58/mm(2) in skin of the posterior forearm. Terminal Schwann cells showed a marker profile comparable to Schwann cells in peripheral nerves with the notable exception of expression of NGFr, NCAM, L1CAM and CD146 on myelinating Schwann cells in the dermis but not in peripheral nerves. Our data show that terminal Schwann cells constitute a substantial cell population within the papillary dermis and that both nerve fiber length and Schwann cell numbers vary considerably between different body sites. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Relating retinal nerve fiber thickness to behavioral sensitivity in patients with glaucoma: application of a linear model.

PubMed

Hood, Donald C

2007-05-01

Glaucoma causes damage to the retinal ganglion cells and their axons, and this damage can be detected with both structural and functional tests. The purpose of this study was to better understand the relationship between a structural measure of retinal nerve fiber layer (RNFL) and the most common functional test, behavioral sensitivity with static automated perimetry (SAP). First, a linear model, previously shown to describe the relationship between local visual evoked potentials and SAP sensitivity, was modified to predict the change in RNFL as measured by optical coherence tomography. Second, previous work by others was shown to be consistent with this model.

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

NASA Astrophysics Data System (ADS)

Yoo, Paul B.; Lubock, Nathan B.; Hincapie, Juan G.; Ruble, Stephen B.; Hamann, Jason J.; Grill, Warren M.

2013-04-01

Objective. Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. Approach. In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. Main results. Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. Significance. Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

Myoneural necrosis following high-frequency electrical stimulation of the cast-immobilized rabbit hindlimb

NASA Technical Reports Server (NTRS)

Friden, J.; Lieber, R. L.; Myers, R. R.; Powell, H. C.; Hargens, A. R.

1989-01-01

The morphological and physiological effects of 4 weeks of high-frequency electrical stimulation (1 h/day, 5 days/week) on cast-immobilized rabbit hindlimbs were investigated in the tibialis anterior muscle and peroneal nerve. In 2 out of 6 animals, high-frequency stimulation with immobilization caused muscle fiber death, internalization of muscle fiber nuclei, connective tissue proliferation, inflammatory response, altered fiber size distribution and variable staining intensities. The fast-twitch fibers were predominantly affected. Two of six peripheral nerves subjected to immobilization and stimulation showed severe damage. Tetanic forces were significantly reduced in the affected muscles. Therefore, the immobilization and high-frequency stimulation may be detrimental to myoneural structure and function and, thus, this combination of therapies should be applied conservatively.

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

PubMed

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

2000-01-01

The aim of this study was to investigate the response of intradental A- and C-fibers during tooth cutting by Er:YAG laser. Bipolar electrical stimulation was applied to the cat's canine to identify functional single nerve fibers of the inferior alveolar nerve. The tip of the canine tooth was cut in 0.5-mm steps until the pulp was exposed. Teeth were alternately cut by using Er:YAG laser (50 mJ, 5 pps) and micromotor under water cooling. The nerve response recorded from the single nerve fibers during laser cutting was compared with that during micromotor cutting. All 26 A-fibers responded to laser cutting with high frequency of nerve firings. The nerve firing rate was significantly higher during laser cutting compared with that during micromotor cutting of superficial dentin (Chi(2) test, P < 0.05) but was not significantly different at deep dentin (P > or = 0. 05). Nine of 11 C-fibers responded to laser cutting when the deep dentin was cut. Among those nine nerve fibers, three also showed a low frequency response to laser cutting of the superficial dentin. During the tooth cutting, Er:YAG laser was more effective in activating intradental A-fibers compared with micromotor and also caused the activation of intradental C-fibers. Copyright 2000 Wiley-Liss, Inc.

INCOMPLETE REPAIR OF RETINAL STRUCTURE AFTER VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING.

PubMed

Hisatomi, Toshio; Tachibana, Takashi; Notomi, Shoji; Nakatake, Shunji; Fujiwara, Kohta; Murakami, Yusuke; Ikeda, Yasuhiro; Yoshida, Shigeo; Enaida, Hiroshi; Murata, Toshinori; Sakamoto, Taiji; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2017-08-01

To examine retinal changes after vitrectomy with internal limiting membrane (ILM) peeling, we used a cynomolgus monkey model and focused on surgical damages of ILM peeling for long observational period of 3 years. Vitrectomy was performed followed by ILM peeling similar to clinical settings in humans. Ultrastructural changes of the retina were investigated by light, transmission, and scanning electron microscopy at 3 months and 3 years after ILM peeling. Ultrastructural study showed that the ILM peeled area was still clearly recognized after 3 years. The Müller cell processes covered most of the retina; however, the nerve fiber layer was partly uncovered and exposed to the vitreous space. The arcuate linear nerve fiber bundles were observed as comparable with dissociated optic nerve fiber layer appearance. Small round retinal surface defects were also observed around macula, resembling the dimple sign. Forceps-related retinal thinning was also found on the edge of ILM peeling, where we started peeling with fine forceps. The ultrastructural studies showed that most of ILM peeling area was covered with glial cells during wound healing processes. Retinal changes were found comparable with dissociated optic nerve fiber layer appearance or dimple sign, which were clinically observed with optical coherence tomography.

Glaucoma-related Changes in the Mechanical Properties and Collagen Micro-architecture of the Human Sclera

PubMed Central

Coudrillier, Baptiste; Pijanka, Jacek K.; Jefferys, Joan L.; Goel, Adhiraj; Quigley, Harry A.; Boote, Craig; Nguyen, Thao D.

2015-01-01

Objective The biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras. Methods Twenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific representation of the collagen structure, were constructed from the DIC-measured geometry. An inverse finite element analysis was developed to estimate the stiffness of the collagen fiber and inter-fiber matrix. Results The differences between glaucoma and non-glaucoma eyes were small in magnitude. Sectorial variations of degree of fiber alignment and peripapillary scleral strain significantly differed between normal and diagnosed glaucoma specimens. Meridional strains were on average larger in diagnosed glaucoma eyes compared with normal specimens. Non-glaucoma specimens had on average the lowest matrix and fiber stiffness, followed by undamaged glaucoma eyes, and damaged glaucoma eyes but the differences in stiffness were not significant. Conclusion The observed biomechanical and microstructural changes could be the result of tissue remodeling occuring in glaucoma and are likely to alter the mechanical environment of the optic nerve head and contribute to axonal damage. PMID:26161963

Evaluation of retinal nerve fiber layer thickness in the area of apparently normal hemifield in glaucomatous eyes with optical coherence tomography.

PubMed

Kee, Changwon; Cho, Changhwan

2003-06-01

The authors investigated the correlation between visual field defects detected by automated perimetry and the thickness of the retinal nerve fiber layer measured with optical coherence tomography, and examined whether there is a decrease in retinal nerve fiber layer thickness in the apparently normal hemifield of glaucomatous eyes. Forty-one patients with glaucoma and 41 normal control subjects were included in this study. Statistical correlations between the sum of the total deviation of 37 stimuli of each hemifield and the ratio of decrease in retinal nerve fiber layer thickness were evaluated. The statistical difference between the retinal nerve fiber layer thickness of the apparently normal hemifield in glaucomatous eyes and that of the corresponding hemifield in normal subjects was also evaluated. There was a statistically significant correlation in the sum of the total deviation and retinal nerve fiber layer thickness decrease ratio (superior hemifield, P = 0.001; inferior hemifield, P = 0.003). There was no significant decrease in retinal nerve fiber layer thickness in the area that corresponded to the normal visual field in the hemifield defect with respect to the horizontal meridian in glaucomatous eyes (superior side, P = 0.148; inferior side, P = 0.341). Optical coherence tomography was capable of demonstrating and measuring retinal nerve fiber layer abnormalities. No changes in the retinal nerve fiber layer thickness of the apparently normal hemifield were observed in glaucomatous eyes.

Adenosine triphosphatase activity of cutaneous nerve fibers.

PubMed

Idé, C; Saito, T

1980-02-01

The histochemical study of Mg++-activated adenosine triphosphatase (Mg++-ATPase) activity was carried out on the peripheral nerves of mouse digital skin by light and electron microscopy. Under the light microscope, the ATPase activity was clearly demonstrated on the nerve fibers as a fine network in the subepidermal regions. Under the electron microscope, the reaction product of enzyme activity was located in the interspace between axolemma and the surrounding Schwann cells of the unmyelinated nerve fibers. No reaction product was observed in the space between the axolemma and the Schwann cells associated with myelinated nerve fibers. Demonstrable activity was absent at the nodes of Ranvier as well as on the para- and internodal regions of these myelinated axons. The part of the axolemma lacking a Schwann cell sheath failed to show a reaction product. The perineural epithelial cells surrounding the nerve fibers displayed reaction product in the caveolae. These results suggest a functional difference in the axon-Schwann interface of myelinated as compared to unmyelinated nerve fibers. The function of the perineural epithelial cell would be expected to be a regulatory one in transferring materials across the epithelium to keep the proper humoral environment around nerve fibers.

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

PubMed

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.

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

PubMed

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.

Corneal subbasal nerve fiber regeneration in myopic patients after laser in situ keratomileusis★

PubMed Central

Deng, Shijing; Wang, Mengmeng; Zhang, Fengju; Sun, Xuguang; Hou, Wenbo; Guo, Ning

2012-01-01

A total of 26 myopic patients (52 eyes) underwent laser in situ keratomileusis. In vivo confocal microscopy revealed that most of the regenerated corneal subbasal nerve fibers in the corneal flap originated from the stump of corneal subbasal nerve fibers outside the ablation zone and extended towards the center of the cornea in all patients. Meanwhile, new fibers were also found to directly regenerate from deep in the stroma in some cases. Approximately 94% of regenerated corneal subbasal nerve fibers (73/78 eyes) regrew vertically into the peripheral central 6-mm circle area 1 month after surgery, 78% (28/36 eyes) grew into the central 3–6 mm area at 2 months, and 23% into the central 3-mm circle area at 3 months. In addition, there was no significant difference in corneal subbasal nerve fiber regenerative capacity between the basic fibroblast growth factor group and the 20% (v/v) deproteinized extract of calf blood group. The majority of corneal subbasal nerve fiber regeneration occurred from the stump of corneal subbasal nerve fibers outside the corneal flap, and the remaining growth occurred deep within the stroma. PMID:25657693

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

PubMed

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

2015-04-01

We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy. For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire. A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs. 26.8 ± 5.9 mm/mm2, P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs. 118.1 ± 55.9 branches/mm2 , P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of 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 in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations. © 2015 American Headache Society.

Corneal confocal microscopy detects small fiber neuropathy in CMT1A patients

PubMed Central

Tavakoli, Mitra; Marshall, Andy; Banka, Siddharth; Petropoulos, Ioannis N; Fadavi, Hassan; Kingston, Helen; Malik, Rayaz A

2012-01-01

Although unmyelinated nerve fibers are affected in CMT1A, they have not been studied in detail due to the invasive nature of the techniques needed to study them. We established alterations in C-fiber bundles of the cornea in patients with CMT1A using non-invasive corneal confocal microscopy (CCM). Twelve patients with CMT1A and twelve healthy control subjects underwent assessment of neuropathic symptoms and deficits, electrophysiology, quantitative sensory testing, corneal sensitivity and corneal confocal microscopy. Corneal sensitivity, corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length and corneal nerve fiber tortuosity were significantly reduced in CMT1A patients compared to controls. There was a significant correlation between corneal sensation and CCM parameters with the severity of painful neuropathic symptoms, cold and warm thresholds and median nerve CMAP amplitude. CCM demonstrates significant damage to C-fiber bundles, which relates to some measures of neuropathy in CMT1A patients. PMID:22996176

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

PubMed

Szlavik, Robert B

2016-02-01

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

Identification of the origin of adrenergic and cholinergic nerve fibers within the superior hypogastric plexus of the human fetus

PubMed Central

Zaitouna, Mazen; Alsaid, Bayan; Diallo, Djibril; Benoit, Gérard; Bessede, Thomas

2013-01-01

Nerve fibers contributing to the superior hypogastric plexus (SHP) and the hypogastric nerves (HN) are currently considered to comprise an adrenergic part of the autonomic nervous system located between vertebrae (T1 and L2), with cholinergic aspects originating from the second to fourth sacral spinal segments (S2, S3 and S4). The aim of this study was to identify the origin and the nature of the nerve fibers within the SHP and the HN, especially the cholinergic fibers, using computer-assisted anatomic dissection (CAAD). Serial histological sections were performed at the level of the lumbar spine and pelvis in five human fetuses between 14 and 30 weeks of gestation. Sections were treated with histological staining [hematoxylin-eosin (HE) and Masson's trichrome (TriM)] and with immunohistochemical methods to detect nerve fibers (anti-S100), adrenergic fibers (anti-TH), cholinergic fibers (anti-VAChT) and nitrergic fibers (anti-nNOS). The sections were then digitalized using a high-resolution scanner and the 3D images were reconstructed using winsurf software. These experiments revealed the coexistence of adrenergic and cholinergic fibers within the SHP and the HNs. One-third of these cholinergic fibers were nitrergic fibers [anti-VACHT (+)/anti-NOS (+)] and potentially pro-erectile, while the others were non-nitrergic [anti-VACHT (+)/anti-NOS (−)]. We found these cholinergic fibers arose from the lumbar nerve roots. This study described the nature of the SHP nerve fibers which gives a better understanding of the urinary and sexual dysfunctions after surgical injuries. PMID:23668336

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

PubMed

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

2015-09-01

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

Peripapillary nerve fiber layer thickness measurement reproducibility using optical coherence tomography.

PubMed

Villain, Max A; Greenfield, David S

2003-01-01

To assess reproducibility of quadrantic and clock hour sectors of retinal nerve fiber layer thickness in normal eyes using optical coherence tomography. Normal eyes of healthy volunteers meeting eligibility criteria were imaged by two inexperienced operators. Six 360 degrees circular scans with a diameter of 3.4 mm centered on the optic disc were obtained during each scanning session, and a baseline image was formed using 3 high-quality images defined by the software. Images were obtained on three different days within a 4-week period. Variance and coefficient of variation (CV) were calculated for quadrantic and retinal nerve fiber layer clock hour sectors obtained from the baseline image. Five normal eyes were scanned. Intraoperator reproducibility was high. The mean (+/- SD) CV for total retinal nerve fiber layer thickness was 5.3 +/- 3.82% and 4.33 +/- 3.7% for operators 1 and 2, respectively. Interoperator reproducibility was good with statistically similar variance for all quadrantic and clock hour retinal nerve fiber layer parameters (P = .42 to .99). The nasal retinal nerve fiber layer was the most variable sector for both operators (mean CV: 10.42% and 7.83% for operators 1 and 2, respectively). Differences in mean total, nasal, temporal, and superior retinal nerve fiber layer thickness were not statistically significant between operators for all eyes; however, for inferior retinal nerve fiber layer thickness, there was a significant (P = .0007) difference between operators in one eye. Peripapillary retinal nerve fiber layer thickness assessments using optical coherence tomography have good intraoperator and interoperator reproducibility. Inexperienced operators can generate useful measurement data with acceptable levels of variance.

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

PubMed

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 controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.

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

PubMed

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.

A simple immunofluorescence technique for simultaneous visualization of mast cells and nerve fibers reveals selectivity and hair cycle--dependent changes in mast cell--nerve fiber contacts in murine skin.

PubMed

Botchkarev, V A; Eichmüller, S; Peters, E M; Pietsch, P; Johansson, O; Maurer, M; Paus, R

1997-04-01

Close contacts between mast cells (MC) and nerve fibers have previously been demonstrated in normal and inflamed skin by light and electron microscopy. A key step for any study in MC-nerve interactions in situ is to simultaneously visualize both communication partners, preferably with the option of double labelling the nerve fibers. For this purpose, we developed the following triple-staining technique. After paraformaldehyde-picric acid perfusion fixation, cryostat sections of back skin from C57BL/6 mice were incubated with a primary rat monoclonal antibody to substance P (SP), followed by incubation with a secondary goat-anti-rat TRITC-conjugated IgG. A rabbit antiserum to CGRP was then applied, followed by a secondary goat-anti-rabbit FITC-conjugated IgG. MCs were visualized by incubation with AMCA-labelled avidin, or (for a more convenient quantification of close MC-nerve fiber contacts) with a mixture of TRITC- and FITC-labelled avidins. Using this simple, novel covisualization method, we were able to show that MC-nerve associations in mouse skin are, contrary to previous suggestions, highly selective for nerve fiber types, and that these interactions are regulated in a hair cycle-dependent manner: in telogen and early anagen skin, MCs preferentially contacted CGRP-immunoreactive (IR) or SP/CGRP-IR double-labelled nerve fibers. Compared with telogen values, there was a significant increase in the number of close contacts between MCs and tyrosine hydroxylase-IR fibers during late anagen, and between MCs and peptide histidine-methionine-IR and choline acetyl transferase-IR fibers during catagen.

Motor unit and muscle fiber type grouping after peripheral nerve injury in the rat.

PubMed

Gordon, Tessa; de Zepetnek, Joanne E Totosy

2016-11-01

Muscle unit (MU) fibers innervated by one motoneuron and corresponding muscle fiber types are normally distributed in a mosaic. We asked whether, 4-8months after common peroneal nerve transection and random surgical alignment of nerve stumps in rat tibialis anterior muscles 1) reinnervated MU muscle and muscle fiber type clumping is invariant and 2) slow and fast motoneurons regenerate their nerve fibers within original endoneurial pathways. MU contractile forces were recorded in vivo, the MUs classified into types according to their contractile speed and fatigability, and one MU subjected to alternate exhaustive stimulation-recovery cycles to deplete glycogen for histochemical MU fiber recognition and enumeration, and muscle fiber typing. MU muscle fibers occupied defined territories whose size increased with MU force and muscle fiber numbers in normal and reinnervated muscles. The reinnervated MU muscle fiber territories were significantly smaller, the fibers clumped within 1-3 groups in 90% of the MUs, and each fiber lying adjacent to another significantly more frequently. Most reinnervated slow muscle fibers were normally located in the deep muscle compartment but substantial numbers were located abnormally in the superficial compartment. Our findings that well reinnervated muscle fibers clump in small muscles contrast with our earlier findings of clumping in large muscles only when reinnervated MU numbers were significantly reduced. We conclude that fiber type clumping is predictive of muscle reinnervation in small but not large muscles. In the latter muscles, clumping is more indicative of sprouting after partial nerve injuries than of muscle reinnervation after complete nerve injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

Retinal nerve fiber layer changes after LASIK evaluated with optical coherence tomography.

PubMed

Dementyev, Dmitriy D; Kourenkov, Vyacheslav V; Rodin, Alexander S; Fadeykina, Tatyana L; Diaz Martines, Tatyana E

2005-01-01

To determine whether the increase in intraocular pressure (IOP) during LASIK suction can induce a decrease in retinal nerve fiber layer thickness assessed by optical coherence tomography (OCT). Nineteen patients (38 eyes) were enrolled in the study. Intraocular pressure was normal at all pre- and postoperative examinations. Retinal nerve fiber layer thickness was measured using OCT-3 Stratus prior to and 1 week and 3 months after LASIK. Laser in situ keratomileusis was performed using the Bausch & Lomb Hansatome microkeratome and the NIDEK EC-5000 excimer laser. Optical coherence tomography mean retinal nerve fiber layer thickness values before and after LASIK were compared using the Student paired t test. Mean patient age was 27.8 years (range: 18 to 33 years). Mean preoperative spherical equivalent refractive error was -4.9 diopters (D) (range: -2.0 to -8.5 D). Mean time of microkeratome suction was 30 seconds (range: 20 to 50 seconds). Preoperatively, the mean retinal nerve fiber layer thickness obtained by OCT was 104.2+/-9.0 microm; at 1 week postoperatively the mean thickness was 101.9+/-6.9 microm, and 106.7+/-6.1 microm at 3 months postoperatively. Mean retinal nerve fiber layer thicknesses obtained by OCT were not significantly different between preoperative and 1 week and 3 months after LASIK (P > or = .05). Laser in situ keratomileusis performed on young myopic patients does not have a significant effect on retinal nerve fiber layer thickness determined by OCT. Further studies are required to reveal the risk of possible optic nerve or retinal nerve fiber layer damage by elevated IOP during LASIK.

Distribution of CGRP and TRPV2 in Human Paranasal Sinuses.

PubMed

Sato, Tadasu; Sasahara, Nobuyuki; Kanda, Noriyuki; Sasaki, Yu; Yamaguma, Yu; Kokubun, Souichi; Yajima, Takehiro; Ichikawa, Hiroyuki

2017-01-01

Immunohistochemistry for protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP) and the transient receptor potential cation channel subfamily V member 2 (TRPV2) was performed on human paranasal sinuses. It was found that in the paranasal sinuses, mucous membranes contain PGP 9.5-immunoreactive (PGP 9.5-IR) nerve fibers. Such nerve fibers terminated around large blood vessels as fine varicosities. Isolated PGP 9.5-IR nerve fibers were scattered beneath the epithelium. Glandular tissues were also innervated by PGP 9.5-IR nerve fibers. These fibers were numerous in the maxillary and ethmoid sinuses, and relatively rare in the frontal and sphenoid sinuses. CGRP-IR nerve fibers were common in the maxillary sinus whereas TRPV2-IR nerve fibers were abundant in the ethmoid sinus. They were located around large blood vessels in the lamina propria. Many subepithelial nerve fibers contained TRPV2 immunoreactivity in the ethmoid sinus. CGRP- and TRPV2-IR nerve fibers were very infrequent in the frontal and sphenoid sinuses. In the human trigeminal ganglion (TG), sensory neurons contained CGRP or TRPV2 immunoreactivity. CGRP-IR TG neurons were more common than TRPV2-IR TG neurons. CGRP-IR TG neurons were of various cell body sizes, whereas TRPV2-IR TG neurons were mostly medium-to-large. In addition, human spinal and principal trigeminal sensory nuclei contained abundant CGRP- and TRPV2-IR varicosities. This study indicates that CGRP- and TRPV2-containing TG neurons probably innervate the paranasal sinus mucosae, and project into spinal and principal trigeminal sensory nuclei. © 2016 S. Karger AG, Basel.

Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

PubMed

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.

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

PubMed Central

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

2012-01-01

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

[Efferent innervation of the arteries of human leptomeninx in arterial hypertension].

PubMed

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

2009-01-01

Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.

Mu-opiate receptor and Beta-endorphin expression in nerve endings and keratinocytes in human skin.

PubMed

Bigliardi-Qi, M; Sumanovski, L T; Büchner, S; Rufli, T; Bigliardi, P L

2004-01-01

We have previously shown that human epidermal keratinocytes express a functionally active micro-opiate receptor, which adds a new dimension to the recently developed research in neuroimmunodermatology and neurogenic inflammation in skin diseases. Human keratinocytes specifically bind and also produce beta-endorphin, the endogenous micro-opiate receptor ligand. Using confocal imaging microscopy, we could now demonstrate that micro-opiate receptors are not only expressed in keratinocytes, but also on unmyelinated peripheral nerve fibers in the dermis and epidermis. Some of the peripheral nerve fibers also express the ligand beta-endorphin. The keratinocytes positive for beta-endorphin staining are clustered around the terminal ends of the unmyelinated nerve fibers. Therefore the opiate receptor system seems to be crucial in the direct communication between nerves and skin. The keratinocytes can influence the unmyelinated nerve fibers in the epidermis directly via secreting beta-endorphin. On the other hand, nerve fibers can also secrete beta-endorphin and influence the migration, differentiation and probably also the cytokine production pattern of keratinocytes.

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

PubMed

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

1989-08-01

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

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

PubMed

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.

Effects of stochastic sodium channels on extracellular excitation of myelinated nerve fibers.

PubMed

Mino, Hiroyuki; Grill, Warren M

2002-06-01

The effects of the stochastic gating properties of sodium channels on the extracellular excitation properties of mammalian nerve fibers was determined by computer simulation. To reduce computation time, a hybrid multicompartment cable model including five central nodes of Ranvier containing stochastic sodium channels and 16 flanking nodes containing detenninistic membrane dynamics was developed. The excitation properties of the hybrid cable model were comparable with those of a full stochastic cable model including 21 nodes of Ranvier containing stochastic sodium channels, indicating the validity of the hybrid cable model. The hybrid cable model was used to investigate whether or not the excitation properties of extracellularly activated fibers were influenced by the stochastic gating of sodium channels, including spike latencies, strength-duration (SD), current-distance (IX), and recruitment properties. The stochastic properties of the sodium channels in the hybrid cable model had the greatest impact when considering the temporal dynamics of nerve fibers, i.e., a large variability in latencies, while they did not influence the SD, IX, or recruitment properties as compared with those of the conventional deterministic cable model. These findings suggest that inclusion of stochastic nodes is not important for model-based design of stimulus waveforms for activation of motor nerve fibers. However, in cases where temporal fine structure is important, for example in sensory neural prostheses in the auditory and visual systems, the stochastic properties of the sodium channels may play a key role in the design of stimulus waveforms.

Muscarinic acetylcholine receptor subtype expression in avian vestibular hair cells, nerve terminals and ganglion cells.

PubMed

Li, G Q; Kevetter, G A; Leonard, R B; Prusak, D J; Wood, T G; Correia, M J

2007-04-25

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the CNS and peripheral nervous system and play an important role in modulating the cell activity and function. We have shown that the cholinergic agonist carbachol reduces the pigeon's inwardly rectifying potassium channel (pKir2.1) ionic currents in native vestibular hair cells. We have cloned and sequenced pigeon mAChR subtypes M2-M5 and we have studied the expression of all five mAChR subtypes (M1-M5) in the pigeon vestibular end organs (semicircular canal ampullary cristae and utricular maculae), vestibular nerve fibers and the vestibular (Scarpa's) ganglion using tissue immunohistochemistry (IH), dissociated single cell immunocytochemistry (IC) and Western blotting (WB). We found that vestibular hair cells, nerve fibers and ganglion cells each expressed all five (M1-M5) mAChR subtypes. Two of the three odd-numbered mAChRs (M1, M5) were present on the hair cell cilia, supporting cells and nerve terminals. And all three odd numbered mAChRs (M1, M3 and M5) were expressed on cuticular plates, myelin sheaths and Schwann cells. Even-numbered mAChRs were seen on the nerve terminals. M2 was also shown on the cuticular plates and supporting cells. Vestibular efferent fibers and terminals were not identified in our studies. Results from WB of the dissociated vestibular epithelia, nerve fibers and vestibular ganglia were consistent with the results from IH and IC. Our findings suggest that there is considerable co-expression of the subtypes on the neural elements of the labyrinth. Further electrophysiological and pharmacological studies should delineate the mechanisms of action of muscarinic acetylcholine receptors on structures in the labyrinth.

Coherent anti-Stokes Raman scattering rigid endoscope toward robot-assisted surgery.

PubMed

Hirose, K; Aoki, T; Furukawa, T; Fukushima, S; Niioka, H; Deguchi, S; Hashimoto, M

2018-02-01

Label-free visualization of nerves and nervous plexuses will improve the preservation of neurological functions in nerve-sparing robot-assisted surgery. We have developed a coherent anti-Stokes Raman scattering (CARS) rigid endoscope to distinguish nerves from other tissues during surgery. The developed endoscope, which has a tube with a diameter of 12 mm and a length of 270 mm, achieved 0.91% image distortion and 8.6% non-uniformity of CARS intensity in the whole field of view (650 μm diameter). We demonstrated CARS imaging of a rat sciatic nerve and visualization of the fine structure of nerve fibers.

[Myelinated nerve fibers coexisted with epiretinal membrane in macula--case report].

PubMed

Swiech-Zubilewicz, Anna; Bieliński, Paweł; Dolar-Szczasny, Joanna; Zarnowski, Tomasz

2012-01-01

We describe a case of peripapillary myelinated retinal nerve fibers complicated by epiretinal membrane in region of macula. 72 years old man was refered to our Clinic with suspicion of retinal detachment of right eye. Visual acuity of right eye was based to 0.05, in left eye was 0.5. IOP was normal in both eyes. In biomcroscopic evaluation the slight cortical cataract was observed in both eyes. Stereoscopic evaluation of right eye revealed the presence of massive peripapillary myelinated retinal nerve fibers and epiretinal membrane in the macula. In the left eye the less intense peripapillary myelinated retinal nerve fibers were noticed as well and the macular region was unchanged. With the use of OCT examination of the retina the presence of epiretinal membrane in the right eye was confirmed. OCT in the fellow eye presented an undisturbed foveal profile without any epiretinal abnormalities. Myelinated retinal nerve fibers can be complicated by epiretinal membrane. Probably the presence of macular pathologies depends on the extensions of nerve fibers. OCT examination is very helpful to give a proper diagnosis.

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

PubMed

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.

Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes.

PubMed

Zellmer, Erik R; MacEwan, Matthew R; Moran, Daniel W

2018-04-01

Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs). A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs. Recruitment thresholds of individual regenerated fibers with diameters  >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90-140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds compared to small fibers. Utilizing regenerated fiber morphometry and caliber distributions resulted in accurate predictions of in vivo recruitment data. Our work uses computational modeling to show how morphometric differences between regenerated and undisrupted tissue results in recruitment threshold discrepancies, quantifies these differences, and illustrates how large undisrupted nerve fibers close to longitudinally restricted current sources have higher recruitment thresholds compared to adjacently positioned smaller fibers while the opposite is true for large regenerated fibers.

Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes

NASA Astrophysics Data System (ADS)

Zellmer, Erik R.; MacEwan, Matthew R.; Moran, Daniel W.

2018-04-01

Objective. Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs). Approach. A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs. Main results. Recruitment thresholds of individual regenerated fibers with diameters  >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90-140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds compared to small fibers. Utilizing regenerated fiber morphometry and caliber distributions resulted in accurate predictions of in vivo recruitment data. Significance. Our work uses computational modeling to show how morphometric differences between regenerated and undisrupted tissue results in recruitment threshold discrepancies, quantifies these differences, and illustrates how large undisrupted nerve fibers close to longitudinally restricted current sources have higher recruitment thresholds compared to adjacently positioned smaller fibers while the opposite is true for large regenerated fibers.

Microstructure of the smart composite structures with embedded fiber optic sensing nerves

NASA Astrophysics Data System (ADS)

Liu, Jingyuan; Luo, Fei; Li, Changchun; Ma, Naibin

1997-11-01

The composite structures with embedded optical fiber sensors construct a smart composite structure system, which may have the characteristics of the in-service self-measurement, self- recognition and self-judgement action. In the present work, we studied the microstructures of carbon/epoxy composite laminates with embedded sensing optical fibers, and the integration of optical fiber with composites was also discussed. The preliminary experiment results show that because of the difference between the sensing optical fibers and the reinforcing fibers in their size, the microstructure of the composites with embedded optical fibers will produce partial local changes in the area of embedded optical fiber, these changes may affect the mechanical properties of composite structures. When the optical fibers are embedded parallel to the reinforcing fibers, due to the composite prepregs are formed under a press action during its curing process, the reinforcing fibers can be arranged equably around the optical fibers. But when the optical fibers are embedded perpendicularly to the reinforcement fibers, the resin rich pocket will appear in the composite laminates surrounding the embedded optical fiber. The gas holes will be easily produced in these zones which may produce a premature failure of the composite structure. The photoelastic experiments are also given in the paper.

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

PubMed

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  < 0.001), while severity is the most important determinant factor of inferior, nasal, and temporal retinal nerve fiber 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.

Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury.

PubMed

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

2010-02-25

We focused on the healing of rat transected sciatic nerve and improvement made by stable gastric pentadecapeptide BPC 157 (10 microg, 10ng/kg) applied shortly after injury (i) intraperitoneally/intragastrically/locally, at the site of anastomosis, or after (ii) non-anastomozed nerve tubing (7 mm nerve segment resected) directly into the tube. Improvement was shown clinically (autotomy), microscopically/morphometrically and functionally (EMG, one or two months post-injury, walking recovery (sciatic functional index (SFI)) at weekly intervals). BPC 157-rats exhibited faster axonal regeneration: histomorphometrically (improved presentation of neural fascicles, homogeneous regeneration pattern, increased density and size of regenerative fibers, existence of epineural and perineural regeneration, uniform target orientation of regenerative fibers, and higher proportion of neural vs. connective tissue, all fascicles in each nerve showed increased diameter of myelinated fibers, thickness of myelin sheet, number of myelinated fibers per area and myelinated fibers as a percentage of the nerve transected area and the increased blood vessels presentation), electrophysiologically (increased motor action potentials), functionally (improved SFI), the autotomy absent. Thus, BPC 157 markedly improved rat sciatic nerve healing. Copyright 2009 Elsevier B.V. All rights reserved.

The Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur.

PubMed

Chartier, Stephane R; Mitchell, Stefanie A T; Majuta, Lisa A; Mantyh, Patrick W

2018-02-10

Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. With aging, the total number of sensory and sympathetic nerve fibers clearly declines as the cambium layer of the periosteum dramatically thins. Yet even in the aging femur, there remains a dense sensory and sympathetic innervation of the periosteum. In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The spinoglenoid ligament. Anatomy, morphology, and histological findings.

PubMed

Plancher, Kevin D; Peterson, Robert K; Johnston, Jack C; Luke, Timothy A

2005-02-01

Dysfunction of the distal branch of the suprascapular nerve has been reported in athletes involved in throwing or overhead sports. The consistent presence of a dynamic anatomic structure, the spinoglenoid ligament, overlying the nerve in the spinoglenoid notch may be a contributing factor to the dysfunction of this nerve. The purpose of this study was to report the anatomy, morphology, and histological characteristics of the spinoglenoid ligament. The spinoglenoid ligaments of fifty-eight fresh-frozen cadaver shoulders were dissected to evaluate their anatomic dimensions, histological characteristics, and relationship to the suprascapular nerve, the posterior part of the capsule, and the glenoid rim. The spinoglenoid ligament was harvested, with its insertions on the scapular spine and on the capsule and glenoid left intact, for the histological analysis. Dissection revealed that a spinoglenoid ligament was present in all specimens. The ligament was found to form an irregular quadrangular shape. On gross examination, the deep fibers of the ligament extended from the lateral aspect of the scapular spine to the posterior part of the glenoid and the superficial fibers blended with the posterior aspect of the shoulder capsule. Histological sections demonstrated Sharpey fibers inserting into bone at the scapular spine and blending with the posterior aspect of the shoulder capsule to insert into the posterior surface of the glenoid, findings that confirmed the ligamentous nature of this structure. This study revealed the presence of the spinoglenoid ligament in all of the shoulders that were examined, with some variation in the size of the ligament.

Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy.

PubMed

Ramírez, Manuel; Martínez-Martínez, Laura-Aline; Hernández-Quintela, Everardo; Velazco-Casapía, Jorge; Vargas, Angélica; Martínez-Lavín, Manuel

2015-10-01

A consistent line of investigation suggests that fibromyalgia is a neuropathic pain syndrome. This outlook has been recently reinforced by several controlled studies that describe decreased small nerve fiber density in skin biopsies of patients with fibromyalgia. The cornea receives the densest small fiber innervation of the body. Corneal confocal bio-microscopy is a new noninvasive method to evaluate small nerve fiber morphology. Our objective was to assess corneal small nerve fiber morphology in patients with fibromyalgia, and to associate corneal nerve microscopic features with neuropathic pain descriptors and other fibromyalgia symptoms. We studied 17 female patients with fibromyalgia and 17 age-matched healthy control subjects. All the participants completed different questionnaires regarding the symptoms of fibromyalgia, including a neuropathic pain survey. A central corneal thickness scan was obtained with a confocal microscope. Nerve measurements were made by a single ophthalmologist without knowledge of the clinical diagnosis. Stromal nerve thickness was defined as the mean value between the widest and the narrowest portion of each analyzed stromal nerve. Corneal sub-basal plexus nerve density was also assessed. Patients with fibromyalgia had stromal nerve thickness of 5.0 ± 1.0 µm (mean ± standard deviation) significantly different from that of control's values (6.1 ± 1.3) p = 0.01. Patients also had decreased sub-basal plexus nerve density per square millimeter (85 ± 29) vs. 107 ± 26 of controls p = 0.02. When controls and patients were grouped together, there was an association between stromal nerve slenderness and neuropathic pain descriptors (Fisher's exact test p = 0.007). Women suffering from fibromyalgia have thinner corneal stromal nerves and diminished sub-basal plexus nerve density when compared to healthy controls. Nerve scarcity is associated with neuropathic pain descriptors. Small fiber neuropathy may play a role in the pathogenesis of fibromyalgia pain. Corneal confocal microscopy could become a useful test in the study of patients with fibromyalgia. Copyright © 2015. Published by Elsevier Inc.

F-actin distribution at nodes of Ranvier and Schmidt-Lanterman incisures in mammalian sciatic nerves.

PubMed

Kun, Alejandra; Canclini, Lucía; Rosso, Gonzalo; Bresque, Mariana; Romeo, Carlos; Hanusz, Alicia; Cal, Karina; Calliari, Aldo; Sotelo Silveira, José; Sotelo, José R

2012-07-01

Very little is known about the function of the F-actin cytoskeleton in the regeneration and pathology of peripheral nerve fibers. The actin cytoskeleton has been associated with maintenance of tissue structure, transmission of traction and contraction forces, and an involvement in cell motility. Therefore, the state of the actin cytoskeleton strongly influences the mechanical properties of cells and intracellular transport therein. In this work, we analyze the distribution of F-actin at Schmidt-Lanterman Incisures (SLI) and nodes of Ranvier (NR) domains in normal, regenerating and pathologic Trembler J (TrJ/+) sciatic nerve fibers, of rats and mice. F-actin was quantified and it was found increased in TrJ/+, both in SLI and NR. However, SLI and NR of regenerating rat sciatic nerve did not show significant differences in F-actin, as compared with normal nerves. Cytochalasin-D and Latrunculin-A were used to disrupt the F-actin network in normal and regenerating rat sciatic nerve fibers. Both drugs disrupt F-actin, but in different ways. Cytochalasin-D did not disrupt Schwann cell (SC) F-actin at the NR. Latrunculin-A did not disrupt F-actin at the boundary region between SC and axon at the NR domain. We surmise that the rearrangement of F-actin in neurological disorders, as presented here, is an important feature of TrJ/+ pathology as a Charcot-Marie-Tooth (CMT) model. Copyright © 2012 Wiley Periodicals, Inc.

Estimating a structural bottle neck for eye-brain transfer of visual information from 3D-volumes of the optic nerve head from a commercial OCT device

NASA Astrophysics Data System (ADS)

Malmberg, Filip; Sandberg-Melin, Camilla; Söderberg, Per G.

2016-03-01

The aim of this project was to investigate the possibility of using OCT optic nerve head 3D information captured with a Topcon OCT 2000 device for detection of the shortest distance between the inner limit of the retina and the central limit of the pigment epithelium around the circumference of the optic nerve head. The shortest distance between these boundaries reflects the nerve fiber layer thickness and measurement of this distance is interesting for follow-up of glaucoma.

In vivo potency of different ligands on voltage-gated sodium channels.

PubMed

Safrany-Fark, Arpad; Petrovszki, Zita; Kekesi, Gabriella; Liszli, Peter; Benedek, Gyorgy; Keresztes, Csilla; Horvath, Gyongyi

2015-09-05

The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Navs), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Navs. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Navs in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative phase and texture angularity analysis of brain white matter lesions in multiple sclerosis

NASA Astrophysics Data System (ADS)

Baxandall, Shalese; Sharma, Shrushrita; Zhai, Peng; Pridham, Glen; Zhang, Yunyan

2018-03-01

Structural changes to nerve fiber tracts are extremely common in neurological diseases such as multiple sclerosis (MS). Accurate quantification is vital. However, while nerve fiber damage is often seen as multi-focal lesions in magnetic resonance imaging (MRI), measurement through visual perception is limited. Our goal was to characterize the texture pattern of the lesions in MRI and determine how texture orientation metrics relate to lesion structure using two new methods: phase congruency and multi-resolution spatial-frequency analysis. The former aims to optimize the detection of the `edges and corners' of a structure, and the latter evaluates both the radial and angular distributions of image texture associated with the various forming scales of a structure. The radial texture spectra were previously confirmed to measure the severity of nerve fiber damage, and were thus included for validation. All measures were also done in the control brain white matter for comparison. Using clinical images of MS patients, we found that both phase congruency and weighted mean phase detected invisible lesion patterns and were significantly greater in lesions, suggesting higher structure complexity, than the control tissue. Similarly, multi-angular spatial-frequency analysis detected much higher texture across the whole frequency spectrum in lesions than the control areas. Such angular complexity was consistent with findings from radial texture. Analysis of the phase and texture alignment may prove to be a useful new approach for assessing invisible changes in lesions using clinical MRI and thereby lead to improved management of patients with MS and similar disorders.

Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy.

PubMed

Szalai, Eszter; Deák, Eszter; Módis, László; Németh, Gábor; Berta, András; Nagy, Annamária; Felszeghy, Eniko; Káposzta, Rita; Malik, Rayaz A; Csutak, Adrienne

2016-03-01

The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy. A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM). We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects. Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

Types of neural guides and using nanotechnology for peripheral nerve reconstruction

PubMed Central

Biazar, Esmaeil; Khorasani, MT; Montazeri, Naser; Pourshamsian, Khalil; Daliri, Morteza; T, Mostafa Rezaei; B, Mahmoud Jabarvand; Khoshzaban, Ahad; K, Saeed Heidari; Jafarpour, Mostafa; Roviemiab, Ziba

2010-01-01

Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Different methods, such as conventional allograft procedures and use of biologic tubes present problems when used for damaged peripheral nerve reconstruction. Designed scaffolds comprised of natural and synthetic materials are now widely used in the reconstruction of damaged tissues. Utilization of absorbable and nonabsorbable synthetic and natural polymers with unique characteristics can be an appropriate solution to repair damaged nerve tissues. Polymeric nanofibrous scaffolds with properties similar to neural structures can be more effective in the reconstruction process. Better cell adhesion and migration, more guiding of axons, and structural features, such as porosity, provide a clearer role for nanofibers in the restoration of neural tissues. In this paper, basic concepts of peripheral nerve injury, types of artificial and natural guides, and methods to improve the performance of tubes, such as orientation, nanotechnology applications for nerve reconstruction, fibers and nanofibers, electrospinning methods, and their application in peripheral nerve reconstruction are reviewed. PMID:21042546

The Overwhelming Majority but not All Motor Fibers of the Bifid Recurrent Laryngeal Nerve are Located in the Anterior Extralaryngeal Branch.

PubMed

Barczyński, Marcin; Stopa, Małgorzata; Konturek, Aleksander; Nowak, Wojciech

2016-03-01

Few small studies reported that motor fibers are located exclusively in the anterior branch of the bifid recurrent laryngeal nerve (RLN). The aim of this study was to investigate the location of the motor fibers to the intrinsic muscles of the larynx among the bifid RLNs, and assess the prevalence of RLN injury with respect to nerve branching in a pragmatic trial. This was a prospective cohort study of 1250 patients who underwent total thyroidectomy with intraoperative neural monitoring. The primary outcome was the position of the motor fibers in the bifid nerves. Adduction of the vocal folds was detected by the endotracheal tube electromyography and abduction by finger palpation of muscle contraction in the posterior cricoarytenoid. The secondary outcomes were the prevalence of the RLN branching and the prevalence of RLN injury in bifid versus non-bifid nerves. The bifid RLNs were identified in 613/2500 (24.5%) nerves at risk, including 92 (7.4%) patients with bilateral bifurcations. The motor fibers were present exclusively in the anterior branch in 605/613 (98.7%) bifid nerves, and in both the RLN branches in 8/613 (1.3%) bifid nerves. Prevalence of RLN injury was 5.2 versus 1.6% for the bifid versus non-bifid nerves (p < 0.001), odds ratio 2.98 (95% confidence interval 1.79-4.95; p < 0.001). The motor fibers of the RLN are located in the anterior extralaryngeal branch in the vast majority of but not in all patients. In rare cases, the motor fibers for adduction or abduction are located in the posterior branch of the RLN. As the bifid nerves are more prone to injury than non-branched nerves, meticulous dissection is recommended to assure preservation of all the branches of the RLN during thyroidectomy.

Sustained reduction in blood pressure from electrical activation of the baroreflex is mediated via the central pathway of unmyelinated baroreceptors.

PubMed

Turner, Michael J; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2014-06-13

This study aims to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fiber (3 V, 20-100 Hz) or C-fiber (20 V, 0-10 Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28 ± 0.04 vs. 4.01 ± 0.2%·Hz(-1), P<0.001) and coherence at 0.01 Hz (0.44 ± 0.05 vs. 0.81 ± 0.03, P<0.05) were significantly lower for A-fiber stimulation compared with C-fiber stimulation. The slope of the dynamic gain was higher for A-fiber stimulation (14.82 ± 1.02 vs. 7.21 ± 0.79 dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fiber stimulation compared with C-fiber stimulation (0.23 ± 0.05 vs. 3.05 ± 0.31 mmHg·Hz(-1), P<0.001). These data indicate that the A-fiber central pathway contributes to high frequency arterial pressure regulation and the C-fiber central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fiber central pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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 < 0.001). MC density (MCD) (P = 0.001), sweat gland nerve fiber density (SGNFD) (P < 0.001), and pilomotor nerve fiber density (PNFD) (P < 0.001) were all reduced in ALS patients. The SGNFD correlated with the small-fiber neuropathy Symptoms Inventory Questionnaire (SFN-SIQ), VAS and age. The SFN-SIQ was higher in ALS with sensory symptoms than without sensory symptoms (P = 0.000). Furthermore, the SFN-SIQ was higher in ALS with autonomic symptoms than without autonomic symptoms (P = 0.002). SFN-SIQ was higher in ALS patients that were pTDP-43 positive than pTDP-43 negative (P = 0.04), respectively. We established in the peripheral nervous system that higher SFN-SIQ and VAS was involved in ALS, indicating the loss of SGNF. The deposition of TDP-43/pTDP-43 in ALS 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.

Scleral anisotropy and its effects on the mechanical response of the optic nerve head

PubMed Central

Coudrillier, Baptiste; Boote, Craig; Quigley, Harry A.

2012-01-01

This paper presents a computational modeling study of the effects of the collagen fiber structure on the mechanical response of the sclera and the adjacent optic nerve head (ONH). A specimen-specific inverse finite element method was developed to determine the material properties of two human sclera subjected to full-field inflation experiments. A distributed fiber model was applied to describe the anisotropic elastic behavior of the sclera. The model directly incorporated wide angle x-ray scattering measurements of the anisotropic collagen structure. The converged solution of the inverse method was used in micromechanical studies of the mechanical anisotropy of the sclera at different scales. The effects of the scleral collagen fiber structure on the ONH deformation were evaluated by progressively filtering out local anisotropic features. It was found that the majority of the midposterior sclera could be described as isotropic without significantly affecting the mechanical response of the tissues of the ONH. In contrast, removing local anisotropic features in the peripapillary sclera produced significant changes in scleral canal expansion, and lamina cribrosa deformation. Local variations in the collagen structure of the peripapillary sclera significantly influenced the mechanical response of the ONH. PMID:23188256

BREAST CANCER-INDUCED BONE REMODELING, SKELETAL PAIN AND SPROUTING OF SENSORY NERVE FIBERS

PubMed Central

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

2011-01-01

Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other non-malignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP+) sensory nerve fibers. Nearly all CGRP+ nerve fibers that undergo sprouting also co-express tropomyosin receptor kinase A (TrkA+) and growth associated protein-43 (GAP43+). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP+ / TrkA+ / GAP43+ sensory nerve fibers. PMID:21497141

Retinotopic and temporal organization of the optic nerve and tracts in the adult goldfish.

PubMed

Bunt, S M

1982-04-10

In order to investigate the role of the different factors controlling the pathways and termination sites of growing axons, selected optic fibers were traced from the eye to the tectum in adult goldfish either by filling them with HRP, or by severing a group of fibers and tracing their degeneration in 2 micrometers plastic sections stained with toluidine blue. Some fish received more than one lesion and others received both lesions and HRP applications. Two major rearrangements of the optic fibers were identified, one at the exit from the eye, the other within the optic tracts. Near the eye the optic fibers appear to be guided by the conformation of the underlying tissue planes that they encounter. The most recently added fibers, from the peripheral retina, grow over the vitread surface of the older fibers toward the blood vessel in the center of the optic nerve head. Behind the eye the fibers follow this blood vessel until it leaves the side of the optic nerve, and the fibers from peripheral retina are left as a single group on the ventral edge of the optic nerve cross section. As a consequence of this pattern of fiber growth the fibers form an orderly temporal sequence in the optic nerve, with the oldest fibers from the central retina on one side of the nerve and the youngest from peripheral retina on the other. In addition, the fibers are ordered topographically at right angles to this central-to-peripheral axis, with fibers from ventral retina on each edge of the nerve, dorsal fibers in the center, and nasal and temporal fibers in between. This arrangement of the optic fibers continues with only a little loss of precision up to the optic tracts. A more radical fiber rearrangement, seemingly incompatible with the fibers simply following tissue planes occurs within the optic tracts. Each newly arriving set of fibers grows over the surface of the optic tracts so that the older fibers come to lie deepest in the tracts. This segregation of fibers of different ages ensures that the rearrangement is limited to each layer of fibers. The abrupt reorganization of the fibers occurs as the tracts split around the nucleus rotundus to form the brachia of the optic tracts. The fibers are then arranged with temporal fibers nearest the nucleus rotundus and nasal fibers on the opposite edges of the brachia. From this point the fibers grow out over the tectal surface to their termination sites with only minimal rearrangements. Therefore the optic fiber rearrangements show evidence of several different sorts of constraints acting on the fibers at separate points in the optic pathway, each contributing to the final orderly arrangement of the fibers on the optic tectum.

[The effect of local ionizing irradiation on the presence of acetylcholinesterase-positive nerve fibers in the spleen of rats].

PubMed

Schmidtová, K; Kluchová, D; Rybárová, S

1998-02-01

Changes in the distribution of ACHE-positive nerve fibres in the spleen of the rat after local irradiation have been studied by light microscopy using direct tiocholin method of El-Badawi and Schenk (1967). ACHE-positive nerve fibers enter the spleen in the vicinity of splenic artery branches and they are gradually distributed in form of perivascular plexuses in the white pulp to the periarterial lymphatic sheath (PALS). One dose of local irradiation of the head of the rat causes changes in the presence and distribution of the ACHE-positive nerve fibres in the spleen of the rat. After an intense decrease or the absence of these fibres during the period of the first days after irradiation, there is an evident restoration of ACHE-positive nerve fibres in the white pulp of the organ. The distribution and topography of these nerve structures is the same as in non-irradiated rats on the 35th day after irradiation. During the following days, there is another evident decrease in ACHE-positive nerve fibres in all described localizations of the spleen. Our findings suggest that the indirect effect of irradiation can affect some changes in innervation of the organ which was not exposed to its direct influence. (Fig. 3, Ref. 13.)

Birefringence measurement of retinal nerve fiber layer using polarization-sensitive spectral domain optical coherence tomography with Jones matrix based analysis

NASA Astrophysics Data System (ADS)

Yamanari, Masahiro; Miura, Masahiro; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

2007-02-01

Birefringence of retinal nerve fiber layer is measured by polarization-sensitive spectral domain optical coherence tomography using the B-scan-oriented polarization modulation method. Birefringence of the optical fiber and the cornea is compensated by Jones matrix based analysis. Three-dimensional phase retardation map around the optic nerve head and en-face phase retardation map of the retinal nerve fiber layer are shown. Unlike scanning laser polarimetry, our system can measure the phase retardation quantitatively without using bow-tie pattern of the birefringence in the macular region, which enables diagnosis of glaucoma even if the patients have macular disease.

Thermally Drawn Fibers as Nerve Guidance Scaffolds

PubMed Central

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

2016-01-01

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

Regeneration of the eighth cranial nerve in the bullfrog, Rana catesbeiana.

PubMed

Newman, A; Honrubia, V

1992-01-01

The present study was done in order to document the ability of the eighth cranial nerve of the bullfrog (Rana catesbeiana) to regenerate, the anatomic characteristics of the regenerated fibers, and the specificity of projections from individual endorgan branches of the nerve. The eighth cranial nerve was sharply transected between the ganglion cells and the brain stem in 40 healthy bullfrogs and allowed to regenerate. Anatomic studies were performed in these animals a minimum of 3 months postoperatively. Horseradish peroxidase was used to label the whole vestibular nerve or its individual endorgan branches. Labeled regenerated fibers could be identified crossing the site of the nerve section and projecting centrally to the vestibular nuclei in a pattern similar to that of normal frogs. Labeling of individual branches showed that regenerated fibers innervated the same specific areas found in normal frogs. Unlike normal animals, both thick and thin fibers projected to the medial nucleus.

Sensory and motor neuropathy in a Border Collie.

PubMed

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.

Corneal Confocal Microscopy Detects Early Nerve Regeneration in Diabetic Neuropathy After Simultaneous Pancreas and Kidney Transplantation

PubMed Central

Tavakoli, Mitra; Mitu-Pretorian, Maria; Petropoulos, Ioannis N.; Fadavi, Hassan; Asghar, Omar; Alam, Uazman; Ponirakis, Georgios; Jeziorska, Maria; Marshall, Andy; Efron, Nathan; Boulton, Andrew J.; Augustine, Titus; Malik, Rayaz A.

2013-01-01

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas–kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques. PMID:23002037

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

PubMed

Krarup, Christian; Rosén, Birgitta; Boeckstyns, Michel; Ibsen Sørensen, Allan; Lundborg, Göran; Moldovan, Mihai; Archibald, Simon J

2017-12-01

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. 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. At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p < 0.001) of control. The sensory nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2% and the amplitudes only to 7 ± 1% (P < 0.001). The areas of SNAPs after tactile stimulation recovered to 61 ± 11% and remained slowed. Touch sensation correlated with SNAP areas (p < 0.005) and was negatively related to the prolongation of tactile latencies (p < 0.01); tactile gnosis was not related to electrophysiological parameters. The recovered function of regenerated peripheral nerve fibers and reinnervated mechanoreceptors may differentially influence recovery of sensory modalities. Touch was affected by the number and function of regenerated fibers and mechanoreceptors. In contrast, tactile gnosis depends on the input and plasticity of the central nervous system (CNS), which may explain the absence of a direct relation between electrophysiological parameters and poor recovery. Dispersed maturation of sensory nerve fibers with desynchronized inputs to the CNS also contributes to the poor recovery of tactile gnosis. Ann Neurol 2017. Ann Neurol 2017;82:940-950. © 2017 American Neurological Association.

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining.

PubMed

Kowtharapu, B S; Winter, K; Marfurt, C; Allgeier, S; Köhler, B; Hovakimyan, M; Stahnke, T; Wree, A; Stachs, O; Guthoff, R F

2017-03-01

PurposeThis study was designed to compare and contrast quantitative data of the human corneal sub-basal nerve plexus (SBP) evaluated by two different methods: in vivo confocal microscopy (IVCM), and immunohistochemical staining of ex vivo donor corneas.MethodsSeven parameters of the SBP in large-scale IVCM mosaicking images from healthy subjects were compared with the identical parameters in ex vivo donor corneas stained by β-III-tubulin immunohistochemistry. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), average weighted corneal nerve fiber tortuosity (CNFTo), corneal nerve connection points (CNCP), average corneal nerve single-fiber length (CNSFL), and average weighted corneal nerve fiber thickness (CNFTh) were calculated using a dedicated, published algorithm and compared.ResultsOur experiments showed significantly higher values for CNFL (50.2 vs 21.4 mm/mm 2 ), CNFD (1358.8 vs 277.3 nerve fibers/mm 2 ), CNBD (847.6 vs 163.5 branches/mm 2 ), CNFTo (0.095 vs 0.081 μm -1 ), and CNCP (49.4 vs 21.6 connections/mm 2 ) in histologically staining specimens compared with IVCM images. In contrast, CNSFL values were higher in IVCM images than in histological specimens (32.1 vs 74.1 μm). No significant difference was observed in CNFTh (2.22 vs 2.20 μm) between the two groups.ConclusionsThe results of this study have shown that IVCM has an inherently lower resolution compared with ex vivo immunohistochemical staining of the corneal SBP and that this limitation leads to a systematic underestimation of several SBP parameters. Despite this shortcoming, IVCM is a vital clinical tool for in vivo characterization, quantitative clinical imaging, and evaluation of the human corneal SBP.

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

PubMed

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.

Mirror-image pain after nerve reconstruction in rats is related to enhanced density of epidermal peptidergic nerve fibers.

PubMed

Kambiz, S; Brakkee, E M; Duraku, L S; Hovius, S E R; Ruigrok, T J H; Walbeehm, E T

2015-05-01

Mirror-image pain is a phenomenon in which unprovoked pain is detected on the uninjured contralateral side after unilateral nerve injury. Although it has been implicated that enhanced production of nerve growth factor (NGF) in the contralateral dorsal root ganglion is important in the development of mirror-image pain, it is not known if this is related to enhanced expression of nociceptive fibers in the contralateral skin. Mechanical and thermal sensitivity in the contralateral hind paw was measured at four different time points (5, 10, 20 and 30weeks) after transection and immediate end-to-end reconstruction of the sciatic nerve in rats. These findings were compared to the density of epidermal (peptidergic and non-peptidergic) nerve fibers on the contralateral hind paw. Mechanical hypersensitivity of the contralateral hind paw was observed at 10weeks PO, a time point in which both subgroups of epidermal nerve fibers reached control values. Thermal hypersensitivity was observed with simultaneous increase in the density of epidermal peptidergic nerve fibers of the contralateral hind paw at 20weeks PO. Both thermal sensitivity and the density of epidermal nerve fibers returned to control values 30weeks PO. We conclude that changes in skin innervation and sensitivity are present on the uninjured corresponding side in a transient pain model. Therefore, the contralateral side cannot serve as control. Moreover, the current study confirms the involvement of the peripheral nervous system in the development of mirror-image pain. Copyright © 2015 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2008-02-01

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

Complex regional pain syndrome type I (RSD): pathology of skeletal muscle and peripheral nerve.

PubMed

van der Laan, L; ter Laak, H J; Gabreëls-Festen, A; Gabreëls, F; Goris, R J

1998-07-01

Reflex sympathetic dystrophy (RSD) (recently reclassified as complex regional pain syndrome type I) is a syndrome occurring in extremities and, when chronic, results in severe disability and untractable pain. RSD may be accompanied by neurologic symptoms even when there is no previous neurologic lesion. There is no consensus as to the pathogenic mechanism involved in RSD. To gain insight into the pathophysiology of RSD, we studied histopathology of skeletal muscle and peripheral nerve from patients with chronic RSD in a lower extremity. In eight patients with chronic RSD, an above-the-knee amputation was performed because of a nonfunctional limb. Specimens of sural nerves, tibial nerves, common peroneal nerves, gastrocnemius muscles, and soleus muscles were obtained from the amputated legs and analyzed by light and electron microscopy. In all patients, the affected leg showed similar neurologic symptoms such as spontaneous pain, hyperpathy, allodynia, paresis, and anesthesia dolorosa. The nerves showed no consistent abnormalities of myelinated fibers. In four patients, the C-fibers showed electron microscopic pathology. In all patients, the gastrocnemius and soleus muscle specimens showed a decrease of type I fibers, an increase of lipofuscin pigment, atrophic fibers, and severely thickened basal membrane layers of the capillaries. In chronic RSD, efferent nerve fibers were histologically unaffected; from afferent fibers, only C-fibers showed histopathologic abnormalities. Skeletal muscle showed a variety of histopathologic findings, which are similar to the histologic abnormalities found in muscles of patients with diabetes.

Response properties of the refractory auditory nerve fiber.

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Lihua; Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053; Gan, Li

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 appliedmore » 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 conduits in the field of nerve tissue engineering. - Highlights: • A novel nerve conduit was constructed and applied to repair nerve defect in rats. • Transparent hollow cellulose/soy protein isolate tube was used as conduit matrix. • Pyrroloquinoline quinine was adsorbed into the hollow tube as nerve growth factor. • Schwann cells were cultured into the hollow tube as seed cells. • The new nerve conduit could repair and reconstruct the peripheral nerve defects.« less

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

PubMed

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

Calculation and plotting of retinal nerve fiber paths based on Jansonius et al. 2009/2012 with an R program.

PubMed

Bach, M; Hoffmann, M B

2018-06-01

The data presented in this article are related to the research article entitled "Retinal conduction speed analysis reveals different origins of the P50 and N95 components of the (multifocal) pattern electroretinogram" (Bach et al., 2018) [1]. That analysis required the individual length data of the retinal nerve fibers (from ganglion cell body to optic nerve head, depending on the position of the ganglion cell body). Jansonius et al. (2009, 2012) [2,3] mathematically modeled the path morphology of the human retinal nerve fibers. We here present a working implementation with source code (for the free and open-source programming environment "R") of the Jansonius' formulas, including all errata. One file defines Jansonius et al.'s "phi" function. This function allows quantitative modelling of paths (and any measures derived from them) of the retinal nerve fibers. As a working demonstration, a second file contains a graph which plots samples of nerve fibers. The included R code runs in base R without the need of any additional packages.

African Descent and Glaucoma Evaluation Study (ADAGES)

PubMed Central

Girkin, Christopher A.; Sample, Pamela A.; Liebmann, Jeffrey M.; Jain, Sonia; Bowd, Christopher; Becerra, Lida M.; Medeiros, Felipe A.; Racette, Lyne; Dirkes, Keri A.; Weinreb, Robert N.; Zangwill, Linda M.

2010-01-01

Objective To define differences in optic disc, retinal nerve fiber layer, and macular structure between healthy participants of African (AD) and European descent (ED) using quantitative imaging techniques in the African Descent and Glaucoma Evaluation Study (ADAGES). Methods Reliable images were obtained using stereoscopic photography, confocal scanning laser ophthalmoscopy (Heidelberg retina tomography [HRT]), and optical coherence tomography (OCT) for 648 healthy subjects in ADAGES. Findings were compared and adjusted for age, optic disc area, and reference plane height where appropriate. Results The AD participants had significantly greater optic disc area on HRT (2.06 mm2; P<.001) and OCT (2.47 mm2; P<.001) and a deeper HRT cup depth than the ED group (P<.001). Retinal nerve fiber layer thickness was greater in the AD group except within the temporal region, where it was significantly thinner. Central macular thickness and volume were less in the AD group. Conclusions Most of the variations in optic nerve morphologic characteristics between the AD and ED groups are due to differences in disc area. However, differences remain in HRT cup depth, OCT macular thickness and volume, and OCT retinal nerve fiber layer thickness independent of these variables. These differences should be considered in the determination of disease status. PMID:20457974

Development of the Aortic Baroreflex in Microgravity

NASA Technical Reports Server (NTRS)

Shimizu, Tsuyoshi; Yamasaki, Masao; Waki, Hidefumi; Katsuda, Shin-ichiro; Oishi, Hirotaka; Katahira, Kiyoaki; Nagayama, Tadanori; Miyake, Masao; Miyamoto, Yukako

2003-01-01

Baroreceptors sense pressure in blood vessels and send this information to the brain. The primary baroreceptors are located in the main blood vessel leaving the heart (the aorta) and in the arteries in the neck (the carotid arteries). The brain uses information from the baroreceptors to determine whether blood pressure should be raised or lowered. These reflex responses are called baroreflexes. Changing position within a gravity field (i.e., moving from lying to sitting or standing) powerfully stimulates the baroreflexes. In weightlessness, the amount of stimuli that the baroreflexes receive is dramatically reduced. If this reduction occurs when the pathways that control the baroreflexes are being formed, it is possible that either the structure or function of the baroreceptors may be permanently changed. To study the effect of microgravity on structural and functional development of the aortic baroreflex system, we studied young rats (eight days old at launch) that flew on the Space Shuttle Columbia for 16 days. Six rats were studied on landing day; another six were studied after re-adapting to Earth's gravity for 30 days. On both landing day and 30 days after landing, we tested the sensitivity of the rats' baroreflex response. While the rats were anaesthetized, we recorded their arterial pressure, heart rate, and aortic nerve activity. After the tissues were preserved with perfusion fixation, we also examined the baroreflex structures. On landing day, we found that, compared to the controls, the flight rats had: fewer unmyelinated nerve fibers in their aortic nerves lower baroreflex sensitivity significantly lower contraction ability and wall tension of the aorta a reduced number of smooth muscle cells in the aorta. In the 30-day recovery group, the sensitivity of the baroreflex showed no difference between the flight rats and the control groups, although the unmyelinated fibers of the aortic nerve remained reduced in the flight rats. The results show that spaceflight does affect the development of the aortic baroreflex. The sensitivity of the reflex may be suppressed; however, the function of the blood pressure control system can re-adapt to Earth's gravity if the rats return before maturation. The structural differences in the input pathway of the reflex (Le., the reduction in nerve fibers) may remain permanently.

Dynamic longitudinal investigation of individual nerve endings in the skin of anesthetized mice using in vivo two-photon microscopy

NASA Astrophysics Data System (ADS)

Yuryev, Mikhail; Khiroug, Leonard

2012-04-01

Visualization of individual cutaneous nerve endings has previously relied on laborious procedures of tissue excision, fixation, sectioning and staining for light or electron microscopy. We present a method for non-invasive, longitudinal two-photon microscopy of single nerve endings within the skin of anesthetized transgenic mice. Besides excellent signal-to-background ratio and nanometer-scale spatial resolution, this method offers time-lapse ``movies'' of pathophysiological changes in nerve fine structure over minutes, hours, days or weeks. Structure of keratinocytes and dermal matrix is visualized simultaneously with nerve endings, providing clear landmarks for longitudinal analysis. We further demonstrate feasibility of dissecting individual nerve fibers with infra-red laser and monitoring their degradation and regeneration. In summary, our excision-free optical biopsy technique is ideal for longitudinal microscopic analysis of animal skin and skin innervations in vivo and can be applied widely in preclinical models of chronic pain, allergies, skin cancers and a variety of dermatological disorders.

Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat.

PubMed

Bester, H; Allchorne, A J; Woolf, C J

1998-12-01

Peripheral nerve injury leads to substantial alterations in injured sensory neurons. These include cell death, phenotypic modifications, and regeneration. Primary sensory neurons have recently been shown not to die until a time beyond 4 months following a nerve crush or ligation and this loss is, moreover, limited to cells with unmyelinated axons, the C-fibers. The late loss of C-fibers may be due to a lack of target reinnervation during the regenerative phase. In order to investigate this, we have used a particular peripheral function, unique to C-fibers, as a measure of peripheral reinnervation: an increase in capillary permeability on antidromic activation of C-fibers, i.e., neurogenic extravasation. This was investigated in rats that had received a nerve crush injury 1 to 50 weeks earlier. Some recovery of the capacity of C-fibers to generate extravasation was detected at 8-10 weeks, which increased further at 12-14 weeks, and then plateaued at this level with no further recovery at 30 or 50 weeks. In intact and damaged sciatic nerves, A beta-fibers never induced extravasation. These findings are compatible with the hypothesis that those C-fibers which make it back to their peripheral targets do not subsequently die and those that do not, may die. Copyright 1998 Academic Press.

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

PubMed Central

Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

2016-01-01

Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride.

PubMed

Chen, Wensheng; Zhang, Zhenhao; Hu, Jiaoyue; Xie, Hui; Pan, Juxin; Dong, Nuo; Liu, Zuguo

2013-12-01

To investigate the effect of benzalkonium chloride (BAK) on corneal nerves. Fifty-four adult New Zealand Albino rabbits were randomly divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was applied once daily to 1 eye of each rabbit for 9 days. The contralateral untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining scores were compared with those of control values on days 3, 6, and 9. Corneal whole mounts were immunostained with a specific antitubulin βIII antibody to label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal nerve fiber densities were quantified. The structure of the central cornea was examined by means of in vivo confocal microscopy on day 9. The topical application of BAK resulted in lower corneal sensitivity and higher Rose Bengal staining scores on day 3, whereas there were no significant changes in the BUT, Schirmer, and corneal fluorescein scores. Decreased nerve densities in superficial and subbasal layers were observed in BAK-treated eyes on days 3 and 6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein staining scores on day 9. Corneal superficial epithelial cell size was significantly larger in all BAK-treated eyes compared with that in control eyes. The topical application of BAK can quickly cause corneal hypoesthesia without tear deficiency. Changes in corneal innervation significantly correlate with BAK-induced ocular surface changes.

Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain

PubMed Central

Chartier, Stephane R.; Thompson, Michelle L.; Longo, Geraldine; Fealk, Michelle N.; Majuta, Lisa A.; Mantyh, Patrick W.

2014-01-01

Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in non-healed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+ days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state. PMID:25196264

Renaut bodies in nerves of the trunk of the African elephant, Loxodonta africana.

PubMed

Witter, Kirsti; Egger, Gunter F; Boeck, Peter

2007-05-01

Renaut bodies are loosely textured, cell-sparse structures in the subperineurial space of peripheral nerves, frequently found at sites of nerve entrapment. The trunk of the elephant is a mobile, richly innervated organ, which serves for food gathering, object grasping and as a tactile organ. These functions of the trunk lead to distortion and mechanical compression of its nerves, which can therefore be expected to contain numerous Renaut bodies. Samples of the trunk wall of an adult African elephant (Loxodonta africana) were examined histologically using conventional staining methods, immunohistochemistry, and lectin histochemistry. Architecture of nerve plexuses and occurrence of Renaut bodies in the elephant trunk were compared with those in tissues surrounding the nasal vestibule of the pig. Prominent nerve plexuses were found in all layers of the elephant trunk. Almost all (81%) nerve profiles contained Renaut bodies, a basophilic, discrete subperineurial layer resembling cushions around the nerve core. In contrast, Renaut bodies were seen in only 15% of nerve profiles in the porcine nasal vestibule. Within Renaut bodies, fusiform fibroblasts and round, ruff-like cells were placed into a matrix of acidic glycosaminoglycans with delicate collagen and very few reticular fibers. The turgor of this matrix is thought to protect nerves against compression and shearing strain. Renaut bodies are readily stained with alcian blue (pH 2.5) favorably in combination with immunohistochemical markers of nerve fibers. They should be regarded as a physiological response to repeated mechanical insults and are distinct from pathological alterations. alterations. (c) 2007 Wiley-Liss, Inc.

Molecular Basis of Infrared Detection by Snakes

PubMed Central

Gracheva, Elena O.; Ingolia, Nicolas T.; Kelly, Yvonne M.; Cordero-Morales, Julio F.; Hollopeter, Gunther; Chesler, Alexander T.; Sánchez, Elda E.; Perez, John C.; Weissman, Jonathan S.; Julius, David

2010-01-01

Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a ‘thermal image’ of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibers of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify TRPA1 channels as infrared receptors on sensory nerve fibers that innervate the pit organ. TRPA1 orthologues from pit bearing snakes (vipers, pythons, and boas) are the most heat sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of TRP channels as thermosensors in the vertebrate nervous system. PMID:20228791

Ocular complications associated with local anesthesia administration in dentistry.

PubMed

Boynes, Sean G; Echeverria, Zydnia; Abdulwahab, Mohammad

2010-10-01

The most widely used method for controlling pain during dental procedures is the intraoral administration of local anesthetics in close proximity to a specific nerve or fiber to obtund nerve conduction. The most commonly anesthetized nerves in dentistry are branches or nerve trunks associated with the maxillary and mandibular divisions of the trigeminal nerve (cranial nerve V). However, other nerves may be inadvertently affected by intraoral local anesthesia injections, resulting in anesthetic complications of structures far from the oral cavity. Practitioners should be aware of potential ocular complications following intraoral injections in dentistry. These complications include oculomotor paralysis and vision loss. The knowledge of these conditions and their potential cause should alert the dentist to the importance of appropriate injection techniques and an understanding of management protocol. Copyright © 2010 Elsevier Inc. All rights reserved.

Label-free photoacoustic microscopy of peripheral nerves

NASA Astrophysics Data System (ADS)

Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

2014-01-01

Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-08-01

Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low-back pain. Pain relief using PNFS is dependent on activation of non-nociceptive Aβ-fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation. The extracellular field was estimated using a finite element model based on the geometry of CT scanned lumbar vertebrae. The electrode was modeled as being implanted to a depth of 10-15 mm. Three implant directions were modeled; horizontally, vertically, and diagonally. Both single electrode and "between-lead" stimulation between contralateral electrodes were modeled. The extracellular field was combined with models of sensory Aβ-nerves, motor neurons and muscle fibers to estimate their activation thresholds. The model showed that sensory Aβ fibers could be activated with thresholds down to 0.563 V, and the lowest threshold for motor nerve activation was 7.19 V using between-lead stimulation with the cathode located closest to the nerves. All thresholds for direct muscle activation were above 500 V. The results suggest that direct muscle activation does not occur during PNFS, and concomitant motor and sensory nerve fiber activation are only likely to occur when using between-lead configuration. Thus, it may be relevant to investigate the location of the innervation zone of the low-back muscles prior to electrode implantation to avoid muscle activation. © 2016 International Neuromodulation Society.

Research notes : can bridges have nerves? new technology developing for 'smart' infrastructure.

DOT National Transportation Integrated Search

1998-05-21

In the nerve system, the optical fibers are the information carrier and along their length are the fiber sensors, or nerve endings, which are used to sense the environment. They can be readily incorporated into new construction or retrofitted into ex...

Morphological and neurochemical differences in peptidergic nerve fibers of the mouse vagina.

PubMed

Barry, Christine M; Ji, Esther; Sharma, Harman; Beukes, Lara; Vilimas, Patricia I; DeGraaf, Yvette C; Matusica, Dusan; Haberberger, Rainer V

2017-07-01

The vagina is innervated by a complex arrangement of sensory, sympathetic, and parasympathetic nerve fibers that contain classical transmitters plus an array of neuropeptides and enzymes known to regulate diverse processes including blood flow and nociception. The neurochemical characteristics and distributions of peptide-containing nerves in the mouse vagina are unknown. This study used multiple labeling immunohistochemistry, confocal maging and analysis to investigate the presence and colocalization of the peptides vasoactive intestinal polypeptide (VIP), calcitonin-gene related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and the nitric oxide synthesizing enzyme neuronal nitric oxide synthase (nNOS) in nerve fibers of the murine vaginal wall. We compared cervical and vulvar areas of the vagina in young nullipara and older multipara C57Bl/6 mice, and identified differences including that small ganglia were restricted to cervical segments, epithelial fibers were mainly present in vulvar segments and most nerve fibers were found in the lamina propria of the cervical region of the vagina, where a higher number of fibers containing immunoreactivity for VIP, CGRP, SP, or nNOS were found. Two populations of VIP-containing fibers were identified: fibers containing CGRP and fibers containing VIP but not CGRP. Differences between young and older mice were present in multiple layers of the vaginal wall, with older mice showing overall loss of innervation of epithelium of the proximal vagina and reduced proportions of VIP, CGRP, and SP containing nerve fibers in the distal epithelium. The distal vagina also showed increased vascularization and perivascular fibers containing NPY. Immunolabeling of ganglia associated with the vagina indicated the likely origin of some peptidergic fibers. Our results reveal regional differences and age- or parity-related changes in innervation of the mouse vagina, effecting the distribution of neuropeptides with diverse roles in function of the female genital tract. © 2017 Wiley Periodicals, Inc.

Recurrent laryngeal nerve alterations in developing spontaneously hypertensive rats.

PubMed

da Silva, Greice Anne Rodrigues; Mendes, Vania Alice de Aguiar; Genari, Adriana Borges; Castania, Jaci Ayrton; Salgado, Hélio Cesar; Fazan, Valéria Paula Sassoli

2016-01-01

It is well known that the recurrent laryngeal nerve not only innervates the larynx but also contains baroreceptor fibers, as demonstrated by physiological studies. Because hypertension has a negative impact on both peripheral nerve morphology and the baroreflex, we investigated the recurrent laryngeal nerve morphological alterations related to the development of hypertension. We compared morphological and morphometric aspects of different segments of the recurrent laryngeal nerve in male and female spontaneously hypertensive rats in different ages: 5, 8, and 20 weeks (n = 6 per group). Blood pressure and heart rate were recorded in anesthetized animals, followed by removal of the right and left recurrent laryngeal nerves for epoxy resin embedding and light microscopy analysis. Computer software was used for morphometric analysis. The blood pressure was significantly higher in 20-week-old animals compared to those at 5 weeks. Body weight increased significantly with age, as did the nerve fascicles. For the myelinated fibers and respective axons, there was a reduction of fiber size, more evident on the axon, associated with a reduction of the small myelinated fibers percentage in animals with high blood pressure. Also, 20-week-old animals showed a significant reduction of the blood vessel percentage of occupancy compared to younger ages. No differences were observed between genders. Hypertension development impaired axon growth, affecting mainly the small myelinated fibers. Males and females were affected equally. The alterations of the endoneural blood vessels probably played an important role on the small fibers alterations. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits.

PubMed

Cruz, Yolanda; Hernández-Plata, Isela; Lucio, Rosa Angélica; Zempoalteca, René; Castelán, Francisco; Martínez-Gómez, Margarita

2017-09-01

To determine the anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits. Chinchilla adult anesthetized female rabbits were used. Anatomical, electrophysiological, and histological studies were performed. L7, S1, and some fibers from S2 and S3 form the lumbosacral trunk, which gives origin to the sciatic nerve and innervation to the gluteal region. From S2 to S3 originates the pudendal nerve, whose branches innervates the striated anal and urethra sphincters, as well as the bulbospongiosus, ischiocavernosus, and constrictor vulvae muscles. The sensory field of the pudendal nerve is ∼1800 mm 2 and is localized in the clitoral sheath and perineal and perigenital skin. The organization of the pudendal nerve varies between individuals, three patterns were identified, and one of them was present in 50% of the animals. From S3 emerge the pelvic nerve, which anastomoses to form a plexus localized between the vagina and the rectum. The innervation of the pelvic floor originates from S3 to S4 fibers. Most of the sacral spinal nerves of rabbit are mixed, carrying sensory, and motor information. Sacral nerves innervate the hind limbs, pelvic viscera, clitoris, perineal muscles, inguinal and anal glands and perineal, perigenital, and rump skin. The detailed description of the sacral nerves organization, topography, and axonal components further the knowledge of the innervation in pelvic and perinal structures of the female rabbit. This information will be useful in future studies about the physiology and physiopathology of urinary, fecal, reproductive, and sexual functions. © 2017 Wiley Periodicals, Inc.

Fiber diameter distributions in the chinchilla's ampullary nerves

NASA Technical Reports Server (NTRS)

Hoffman, Larry F.; Honrubia, Vicente

2002-01-01

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

Regeneration of junctional epithelium and its innervation in adult rats: a study using immunocytochemistry for p75 nerve growth factor receptor and calcitonin gene-related peptide.

PubMed

Redd, P E; Byers, M R

1994-05-01

Junctional epithelium (JE) is a rapidly proliferating tissue that connects the gum to the tooth, that provides a free surface for bidirectional movement of substances between the body and the oral cavity, and that participates in defense against bacterial infection. It is innervated by numerous sensory nerve fibers that are immunoreactive (IR) for neuropeptides such as calcitonin gene-related peptide (CGRP), and for low affinity nerve growth factor receptor (p75-NGFR). Basal epithelial cells of the JE and of adjacent sulcular epithelium also have intense p75-NGFR-IR. In the present study we removed a wedge of the free gingiva and JE from the anterior side of the maxillary first molar of adult rats, and then studied the return of nerve fibers during tissue regeneration from 1-63 days after gingivectomy. The nerve fibers entered the adjacent healing sulcular epithelium before innervating the new JE, in both cases prior to return of epithelial cell p75-NGFR-IR. The regenerating nerve fibers completely bypassed the zone of epithelial down-growth (long junctional epithelium, LJE) that was briefly present along the tooth from 1-3 weeks after injury. The LJE did not have p75-NGFR-IR and was gradually replaced by a modified thicker regenerated junctional epithelium (RJE). The RJE was attached along the injured root surface, had numerous nerves in basal layers, and it had begun to regain p75-NGFR-IR staining of basal epithelial cells by 22 d. Regenerating nerve fibers at 6-10 d had unusually weak CGRP-IR and greatly increased p75-NGFR-IR. Both nerve stains had returned to normal by 3-6 weeks. The intense p75-NGFR-IR of regenerating nerves was found on both axonal and Schwann cell membranes using electron microscopic immunocytochemistry. In both the normal and regenerating JE, nerve fibers were rare in the attachment layers next to the anterior side of the maxillary first molar, compared to well-innervated basal layers. The complete avoidance of LJE by regenerating nerve fibers and its lack of p75-NGFR-IR suggest that its functions do not require innervation and that it does not make neurotrophic growth factors.

A morphological and biochemical evaluation of the effects of quercetin on experimental sciatic nerve damage in rats.

PubMed

Türedi, Sibel; Yuluğ, Esin; Alver, Ahmet; Bodur, Akin; İnce, İmran

2018-04-01

The present study evaluated the neuroprotective and antioxidant effects of quercetin in a rat model of sciatic nerve crush injury using histopathological, morphometric and biochemical methods. A total of 48 male Sprague Dawley rats, aged 10-12 weeks old were randomly divided into eight groups, consisting of two sham groups (S-7, S-28), three quercetin-treated groups (Q-7, Q-28; 200 mg/kg/7 days), trauma (T-7, T-28; 1 min sciatic nerve crush injury) and three trauma+quercetin groups (T+Q-7, T+Q-28; trauma+quercetin 200 mg/kg/7 days). Rats were sacrificed on day 7 or 28. Oxidant-antioxidant biochemical parameters in nerve tissues from all groups were analyzed using histopathological staining with toluidine blue and Masson's trichrome. DNA fragmentations were identified using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in cells from each tissue sample. Degeneration of the axons and myelin sheath, the breakdown of the concentric lamellar structure of the myelin sheath and axonal swelling were observed in groups T-7 and T-28. Myelin sheath thicknesses, nerve fiber diameters and the number of myelinated nerve fibers decreased, while the apoptotic index (AI) increased in the T-7 and T-28 groups. However, it was observed that nerve regeneration began in the T+Q-7 and T+Q-28 groups compared with the sham groups, together with the healing of cellular damage and axonal structure and a decrease in the AI. Malondialdehyde and superoxide dismutase activity did not differ significantly between the T-7 and S-7 groups. However, catalase activity significantly decreased in the T-28 group when compared with the sham 7 day group. Tissue malondialdehyde levels significantly increased, while serum catalase activity increased in the T+Q-7 group compared with the T-7 group. These results suggest that quercetin has beneficial effects on nerve regeneration and may shorten the healing period in crush-type sciatic nerve injuries.

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

PubMed

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.

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

PubMed Central

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

2016-01-01

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

Holographic line field en-face OCT with digital adaptive optics in the retina in vivo.

PubMed

Ginner, Laurin; Schmoll, Tilman; Kumar, Abhishek; Salas, Matthias; Pricoupenko, Nastassia; Wurster, Lara M; Leitgeb, Rainer A

2018-02-01

We demonstrate a high-resolution line field en-face time domain optical coherence tomography (OCT) system using an off-axis holography configuration. Line field en-face OCT produces high speed en-face images at rates of up to 100 Hz. The high frame rate favors good phase stability across the lateral field-of-view which is indispensable for digital adaptive optics (DAO). Human retinal structures are acquired in-vivo with a broadband light source at 840 nm, and line rates of 10 kHz to 100 kHz. Structures of different retinal layers, such as photoreceptors, capillaries, and nerve fibers are visualized with high resolution of 2.8 µm and 5.5 µm in lateral directions. Subaperture based DAO is successfully applied to increase the visibility of cone-photoreceptors and nerve fibers. Furthermore, en-face Doppler OCT maps are generated based on calculating the differential phase shifts between recorded lines.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry.

PubMed

Alnawaiseh, Maged; Hömberg, Lisann; Eter, Nicole; Prokosch, Verena

2017-01-01

To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3-6) or the control group (group B: RNFL score 0-2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP.

Neural control of renal function.

PubMed

Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

2011-04-01

The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

Neuropeptide Y in the adult and fetal human pineal gland.

PubMed

Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

Neuropeptide Y in the Adult and Fetal Human Pineal Gland

PubMed Central

Møller, Morten; Phansuwan-Pujito, Pansiri

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally. PMID:24757681

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

PubMed

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 < 0.05) effect of treatment at 6 and 12 weeks postsurgery. At 6 weeks, the fiber density was statistically different between treated and untreated animals with a higher observed density in treated nerves. No difference in fiber density was observed at 12 weeks postsurgery. The distribution of fiber diameters showed an effect at 12 weeks when only the sections of the nerves sutured with PRP showed fibers with diameters greater than 6 µm. Our data show that the application of a PRP fibrin membrane around the 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.

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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.

Enhanced peripheral nerve regeneration by the combination of a polycaprolactone tubular prosthesis and a scaffold of collagen with supramolecular organization

PubMed Central

Maturana, Luiz G; Pierucci, Amauri; Simões, Gustavo F; Vidigal, Mateus; Duek, Eliana A R; Vidal, Benedicto C; Oliveira, Alexandre L R

2013-01-01

The purpose of this study was to investigate the influence of implanting collagen with a supramolecular organization on peripheral nerve regeneration, using the sciatic nerve tubulization technique. For this purpose, adult female Sprague Dawley rats were divided into five groups: (1) TP – sciatic nerve repaired with empty polyethylene tubular prothesis (n = 10), (2) TPCL – nerve repair with empty polycaprolactone (PCL) tubing (n = 8), (3) TPCLF – repair with PCL tubing filled with an implant of collagen with a supramolecular organization (n = 10), (4) AG – animals that received a peripheral nerve autograft (n = 8), and (5) Normal nerves (n = 8). The results were assessed by quantification of the regenerated fibers, nerve morphometry, and transmission electron microscopy, 60 days after surgery. Immunohistochemistry and polarization microscopy were also used to analyze the regenerated nerve structure and cellular elements. The results showed that the AG group presented a larger number of regenerated axons. However, the TPCL and TPCLF groups presented more compact regenerated fibers with a morphometric profile closer to normal, both at the tube midpoint and 2 mm distal to the prosthesis. These findings were reinforced by polarization microscopy, which indicated a better collagen/axons suprastructural organization in the TPCLF derived samples. In addition, the immunohistochemical results obtained using the antibody anti-p75NTR as a Schwann cell reactivity marker demonstrated that the Schwann cells were more reactive during the regenerative process in the TPCLF group as compared to the TPCL group and the normal sciatic nerve. Altogether, the results of this study indicated that the implant of collagen with a supramolecular organization positively influenced and stimulated the regeneration process through the nerve gap, resulting in the formation of a better morphologically arranged tissue. PMID:24381812

The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain.

PubMed

Jimenez-Andrade, Juan M; Mantyh, William G; Bloom, Aaron P; Freeman, Katie T; Ghilardi, Joseph R; Kuskowski, Michael A; Mantyh, Patrick W

2012-05-01

As humans age there is a decline in most sensory systems including vision, hearing, taste, smell, and tactile acuity. In contrast, the frequency and severity of musculoskeletal pain generally increases with age. To determine whether the density of sensory nerve fibers that transduce skeletal pain changes with age, calcitonin gene related peptide (CGRP) and neurofilament 200 kDa (NF200) sensory nerve fibers that innervate the femur were examined in the femurs of young (4-month-old), middle-aged (13-month-old) and old (36-month-old) male F344/BNF1 rats. Whereas the bone quality showed a significant age-related decline, the density of CGRP(+) and NF200(+) nerve fibers that innervate the bone remained remarkably unchanged as did the severity of acute skeletal fracture pain. Thus, while bone mass, quality, and strength undergo a significant decline with age, the density of sensory nerve fibers that transduce noxious stimuli remain largely intact. These data may in part explain why musculoskeletal pain increases with age. Copyright © 2012 Elsevier Inc. All rights reserved.

Collateral development and spinal motor reorganization after nerve injury and repair

PubMed Central

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

2016-01-01

Functional recovery is often unsatisfactory after severe extended nerve defects or proximal nerve trunks injuries repaired by traditional repair methods, as the long regeneration distance for the regenerated axons to reinnervate their original target end-organs. The proximal nerve stump can regenerate with many collaterals that reinnervate the distal stump after peripheral nerve injury, it may be possible to use nearby fewer nerve fibers to repair more nerve fibers at the distal end to shorten the regenerating distance. In this study, the proximal peroneal nerve was used to repair both the distal peroneal and tibial nerve. The number and location of motor neurons in spinal cord as well as functional and morphological recovery were assessed at 2 months, 4 months and 8 months after nerve repair, respectively. Projections from the intact peroneal and tibial nerves were also studied in normal animals. The changes of motor neurons were assessed using the retrograde neurotracers FG and DiI to backlabel motor neurons that regenerate axons into two different pathways. To evaluate the functional recovery, the muscle forces and sciatic function index were examined. The muscles and myelinated axons were assessed using electrophysiology and histology. The results showed that all labeled motor neurons after nerve repair were always confined within the normal peroneal nerve pool and nearly all the distribution of motor neurons labeled via distal different nerves was disorganized as compared to normal group. However, there was a significant decline in the number of double labeled motor neurons and an obvious improvement with respect to the functional and morphological recovery between 2 and 8 months. In addition, the tibial/peroneal motor neuron number ratio at different times was 2.11±0.05, 2.13±0.08, 2.09±0.12, respectively, and was close to normal group (2.21±0.09). Quantitative analysis showed no significant morphological differences between myelinated nerve fibers regenerated along the two distal nerves except for the number of nerve fibers, which was higher in the tibial nerve. The ratio of distal regenerated axon numbers to proximal donor nerve axon numbers was about 3.95±0.10, 4.06±0.19 and 3.87±0.23, respectively. This study demonstrated that fewer nerve fibers can regenerate a large number of collaterals which successfully repopulate both distal nerves and lead to the partial recovery of lost functions. It may provide a new method to repair severe extended nerve defects or proximal nerve trunks injuries. PMID:27508011

Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery.

PubMed

Wozniak, Krystyna M; Vornov, James J; Wu, Ying; Liu, Ying; Carozzi, Valentina A; Rodriguez-Menendez, Virginia; Ballarini, Elisa; Alberti, Paola; Pozzi, Eleonora; Semperboni, Sara; Cook, Brett M; Littlefield, Bruce A; Nomoto, Kenichi; Condon, Krista; Eckley, Sean; DesJardins, Christopher; Wilson, Leslie; Jordan, Mary A; Feinstein, Stuart C; Cavaletti, Guido; Polydefkis, Michael; Slusher, Barbara S

2018-02-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations in preclinical model systems have focused on either behaviors or acute changes in nerve conduction velocity (NCV) and amplitude, but greater understanding of the underlying nature of axonal injury and its long-term processes is needed as cancer patients live longer. In this study, we used multiple independent endpoints to systematically characterize CIPN recovery in mice exposed to the antitubulin cancer drugs eribulin, ixabepilone, paclitaxel, or vinorelbine at MTDs. All of the drugs ablated intraepidermal nerve fibers and produced axonopathy, with a secondary disruption in myelin structure within 2 weeks of drug administration. In addition, all of the drugs reduced sensory NCV and amplitude, with greater deficits after paclitaxel and lesser deficits after ixabepilone. These effects correlated with degeneration in dorsal root ganglia (DRG) and sciatic nerve and abundance of Schwann cells. Although most injuries were fully reversible after 3-6 months after administration of eribulin, vinorelbine, and ixabepilone, we observed delayed recovery after paclitaxel that produced a more severe, pervasive, and prolonged neurotoxicity. Compared with other agents, paclitaxel also displayed a unique prolonged exposure in sciatic nerve and DRG. The most sensitive indicator of toxicity was axonopathy and secondary myelin changes accompanied by a reduction in intraepidermal nerve fiber density. Taken together, our findings suggest that intraepidermal nerve fiber density and changes in NCV and amplitude might provide measures of axonal injury to guide clinical practice. Significance: This detailed preclinical study of the long-term effects of widely used antitubulin cancer drugs on the peripheral nervous system may help guide clinical evaluations to improve personalized care in limiting neurotoxicity in cancer survivors. Cancer Res; 78(3); 817-29. ©2017 AACR . ©2017 American Association for Cancer Research.

Evidence that the extraocular motor nuclei innervate monkey palisade endings.

PubMed

Zimmermann, Lars; May, Paul J; Pastor, Angel M; Streicher, Johannes; Blumer, Roland

2011-02-04

Palisade endings are found in the extraocular muscles (EOMs) of almost every mammalian species, including primates. These nerve specializations surrounding the muscle fiber insertion have been postulated to be the proprioceptors of the EOMs. However, it was recently demonstrated that palisade endings have a cholinergic nature, which reopened the question of whether palisade endings are motor or sensory structures. In this work, we examined whether the cell bodies of palisade endings lie in EOM motor nuclei by injecting an anterograde tracer, biotinylated dextran amine, into the abducens nucleus of a macaque monkey. Tracer visualization in the lateral rectus muscle was combined with choline acetyltransferase (ChAT) and α-bungarotoxin staining. Analysis of the samples was performed by conventional light microscopy and confocal laser scanning microscopy. About 30% of the nerve fibers innervating the muscle were tracer positive. These were ChAT positive as well. Tracer positive nerve fibers established motor contacts on singly and multiply innervated muscle fibers, which were confirmed by α-bungarotoxin staining. At the transition between muscle and distal tendon, we found palisade endings that contained tracer. Palisade endings exhibited the classic morphology: axons arising from the muscle extend onto the tendon, then turn back 180° and terminate in a cuff of terminals around an individual muscle fiber tip. This finding suggests that the cell bodies of palisade endings lie in the EOM motor nuclei, which complements prior studies demonstrating a cholinergic, and possibly motor, phenotype for palisade endings. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Evidence that the extraocular motor nuclei innervate monkey palisade endings

PubMed Central

Zimmermann, Lars; May, Paul J.; Pastor, Ángel M.; Streicher, Johannes; Blumer, Roland

2011-01-01

Palisade endings are found in the extraocular muscles (EOMs) of almost every mammalian species, including primates. These nerve specializations surrounding the muscle fiber insertion have been postulated to be the proprioceptors of the EOMs. However, it was recently demonstrated that palisade endings have a cholinergic nature, which reopened the question of whether palisade endings are motor or sensory structures. In this work, we examined whether the cell bodies of palisade endings lie in EOM motor nuclei by injecting an anterograde tracer, biotinylated dextran amine, into the abducens nucleus of a macaque monkey. Tracer visualization in the lateral rectus muscle was combined with choline acetyltransferase (ChAT) and α-bungarotoxin staining. Analysis of the samples was performed by conventional light microscopy and confocal laser scanning microscopy. About 30% of the nerve fibers innervating the muscle were tracer positive. These were ChAT positive as well. Tracer positive nerve fibers established motor contacts on singly and multiply innervated muscle fibers, which were confirmed by α-bungarotoxin staining. At the transition between muscle and distal tendon, we found palisade endings that contained tracer. Palisade endings exhibited the classic morphology: axons arising from the muscle extend onto the tendon, then turn back 180° and terminate in a cuff of terminals around an individual muscle fiber tip. This finding suggests that the cell bodies of palisade endings lie in the EOM motor nuclei, which complements prior studies demonstrating a cholinergic, and possibly motor, phenotype for palisade endings. PMID:21138754

The neglected cranial nerve: nervus terminalis (cranial nerve N).

PubMed

Vilensky, Joel A

2014-01-01

The nervus terminalis (NT; terminal nerve) was clearly identified as an additional cranial nerve in humans more than a century ago yet remains mostly undescribed in modern anatomy textbooks. The nerve is referred to as the nervus terminalis because in species initially examined its fibers were seen entering the brain in the region of the lamina terminalis. It has also been referred to as cranial nerve 0, but because there is no Roman symbol for zero, an N for the Latin word nulla is a better numerical designation. This nerve is very distinct in human fetuses and infants but also has been repeatedly identified in adult human brains. The NT fibers are unmyelinated and emanate from ganglia. The fibers pass through the cribriform plate medial to those of the olfactory nerve fila. The fibers end in the nasal mucosa and probably arise from autonomic/neuromodulatory as well as sensory neurons. The NT has been demonstrated to release luteinizing-releasing luteinizing hormone and is therefore thought to play a role in reproductive behavior. Based on the available evidence, the NT appears to be functional in adult humans and should be taught in medical schools and incorporated into anatomy/neuroanatomy textbooks. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Detection of a diabetic sural nerve from the magnetic field after electric stimulation

NASA Astrophysics Data System (ADS)

Hayami, Takehito; Iramina, Keiji; Hyodo, Akira; Chen, Xian; Sunagawa, Kenji

2009-04-01

In this study, we proposed a new diagnostic technique for diabetic neuropathy using biomagnetic measurement. Peripheral neuropathy is one of the most common complications of diabetes. To examine the injury, the skin potential around the nerve is often measured after electric stimulation. However, measuring the magnetic field may reveal precise condition of the injury. To evaluate the effect of measuring the magnetic field, a simulation study was performed. A diabetic sural nerve was simulated as a bundle of myelinated nerve fibers. Each fiber was modeled as an electric cable of Ranvier's nodes. Anatomical data were used to determine the number of nerve fibers and distribution of nerve fiber diameters. The electric potential and the magnetic field on the skin after electric stimulation were computed to the boundary element method. Biphasic time courses were obtained as the electric potential and the magnetic flux density at measurement points. In diabetic nerves, the longer interpeak latency of the electric potential wave and the shorter interpeak latency of the magnetic flux wave were obtained. Measuring both the electric potential and the magnetic flux density seemed to provide a noninvasive and objective marker for diabetic neuropathy.

Peripapillary retinal nerve fiber layer thickness in a population of 6-year-old children: findings by optical coherence tomography.

PubMed

Huynh, Son C; Wang, Xiu Ying; Rochtchina, Elena; Mitchell, Paul

2006-09-01

To study the distribution of retinal nerve fiber layer (RNFL) thickness by ocular and demographic variables in a population-based study of young children. Population-based cross-sectional study. One thousand seven hundred sixty-five of 2238 (78.9%) eligible 6-year-old children participated in the Sydney Childhood Eye Study between 2003 and 2004. Mean age was 6.7 years (50.9% boys). Detailed examination included cycloplegic autorefraction and measurement of axial length. Retinal nerve fiber layer scans using an optical coherence tomographer were performed with a circular scan pattern of 3.4-mm diameter. Multivariate analyses were performed to examine the distribution of RNFL parameters with gender, ethnicity, axial length, and refraction. Peripapillary RNFL thickness and RNFL(estimated integral) (RNFL(EI)), which measures the total cross-sectional area of ganglion cell axons converging onto the optic nerve head. Peripapillary RNFL thickness and RNFL(EI) were normally distributed. The mean+/-standard deviation RNFL average thickness was 103.7+/-11.4 microm and RNFL(EI) was 1.05+/-0.12 mm2. Retinal nerve fiber layer thickness was least for the temporal quadrant (75.7+/-14.7 microm), followed by the nasal (81.7+/-19.6 microm), inferior (127.8+/-20.5 microm), and superior (129.5+/-20.6 microm) quadrants. Multivariate adjusted RNFL average thickness was marginally greater in boys than in girls (104.7 microm vs. 103.2 microm; P = 0.007) and in East Asian than in white children (107.7 microm vs. 102.7 microm; P<0.0001). The RNFL was thinner with greater axial length (P(trend)<0.0001) and less positive spherical equivalent refractions (P(trend) = 0.004). Retinal nerve fiber layer average thickness and RNFL(EI) followed a normal distribution. Retinal nerve fiber layer thickness varied marginally with gender, but differences were more marked between white and East Asian children. Retinal nerve fiber layer thinning was associated with increasing axial length and less positive refractions.

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

EPA Science Inventory

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

PATHOLOGICAL SPROUTING OF ADULT NOCICEPTORS IN CHRONIC PROSTATE CANCER-INDUCED BONE PAIN

PubMed Central

Jimenez-Andrade, Juan M.; Bloom, Aaron P.; Stake, James I.; Mantyh, William G.; Taylor, Reid N.; Freeman, Katie T.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

2012-01-01

Pain frequently accompanies cancer. What remains unclear is why this pain frequently becomes more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory nerve fibers that innervate the tumor-bearing tissue undergo a pathological sprouting and reorganization, which in other non-malignant pathologies has been shown to generate and maintain chronic pain. Injection of canine prostate cancer cells into mouse bone induces a remarkable sprouting of calcitonin gene related peptide (CGRP+) and neurofilament 200 kDa (NF200+) sensory nerve fibers. Nearly all sensory nerve fibers that undergo sprouting also co-express tropomyosin receptor kinase A (TrkA+). This ectopic sprouting occurs in sensory nerve fibers that are in close proximity to colonies of prostate cancer cells, tumor-associated stromal cells and newly formed woven bone, which together form sclerotic lesions that closely mirror the osteoblastic bone lesions induced by metastatic prostate tumors in humans. Preventive treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. Interestingly, RT-PCR analysis indicated that the prostate cancer cells themselves do not express detectable levels of mRNA coding for NGF. This suggests that the tumor-associated stromal cells express and release NGF, which drives the pathological reorganization of nearby TrkA+ sensory nerve fibers. Therapies that prevent this reorganization of sensory nerve fibers may provide insight into the evolving mechanisms that drive cancer pain and lead to more effective control of this chronic pain state. PMID:21048122

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

PubMed

Gür Güngör, Sirel; Akman, Ahmet; Sarıgül Sezenöz, Almila; Tanrıaşıkı, Gülşah

2016-12-01

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. 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. 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. 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.

Promoting peripheral nerve regeneration with biodegradable poly (DL-lactic acid) films

PubMed Central

Li, Ruijun; Chen, Lei; Fu, Jinling; Liu, Zhigang; Wang, Shuang; Pan, Yuehai

2015-01-01

Regeneration and repair of peripheral nerve injury has always been a major problem in the clinic. The conventional technique based on suturing the nerve ends to each other coupled with the implantation of nerve conduits outside is associated with postoperative adhesions and scar problems. Recently, a novel biodegradable poly (DL-lactic acid) (PDLLA) film has been introduced. This novel anti-adhesion film has a porous structure with better mechanical properties, better flexibility, and more controllable degradation as compared to traditional non-porous nerve conduits. However, little is known about the effects of such PDLLA films on regeneration and repair of peripheral nerve injury in vivo. In this study, we evaluated the effects of PDLLA films implantation after sciatic nerve transection and anastomosis on subsequent sciatic nerve regeneration in vivo, using a rat sciatic nerve injury model. Sciatic nerve transection surgery coupled with direct suturing only, suturing and wrapping with traditional nerve conduits, or suturing and wrapping with PDLLA films was performed on adult Wistar rats. The additional wrapping with PDLLA films inhibited the nerve adhesion after 12 weeks recovery from surgery. It also increased the compound muscle action potentials and tibialis and gastrocnemius muscle wet weight ratio following 8 weeks recovery from surgery. Regenerated nerve fibers were relatively straight and the aligned structure was complete in rats with implantations of PDLLA films. The results suggested that PDLLA films can improve the nutritional status in the muscles innervated by the damaged nerves and promote nerve regeneration in vivo. PMID:26339372

Innervation pattern of polycystic ovaries in the women.

PubMed

Wojtkiewicz, Joanna; Jana, Barbara; Kozłowska, Anna; Crayton, Robert; Majewski, Mariusz; Zalecki, Michał; Baranowski, Włodzimierz; Radziszewski, Piotr

2014-11-01

The aim of the present study was to determine the changes in both the distribution pattern and density of nerve fibers containing dopamine β-hydroxylase (DβH), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), substance P (SP), calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin (SOM), galanin (GAL) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the human polycystic ovaries. In the polycystic ovaries, when compared to the immunoreactions pattern observed in the control gonads, following changes were revealed: (1) an increase in the number of DβH-, VAChT-, VIP- or GAL-immunoreactive (IR) nerve fibers within the stroma as well as in the number of DβH-IR fibers near primordial follicles and medullar veins and venules; (2) a reduction in the number of nerve fibers containing nNOS, CGRP, SOM, PACAP within the stroma and in the numbers of CGRP-IR fibers around arteries; (3) an appearance of SP- and GAL-IR fibers around medullar and cortical arteries, arterioles, veins and venules, with except of GAL-IR fibers supplying medullar veins; and (4) the lack of nNOS-IR nerve fibers near primordial follicles and VIP-IR nerves around medullar arteries and arterioles. In conclusion, our results suggest that the changes in the innervation pattern of the polycystic ovaries in human may play an important role in the pathogenesis and/or course of this disorder. Copyright © 2014. Published by Elsevier B.V.

Molecular characteristics suggest an effector function of palisade endings in extraocular muscles.

PubMed

Konakci, Kadriye Zeynep; Streicher, Johannes; Hoetzenecker, Wolfram; Blumer, Michael Josef Franz; Lukas, Julius-Robert; Blumer, Roland

2005-01-01

To analyze palisade endings in cat extraocular muscles (EOMs) and to clarify whether these EOM-specific organs are sensory or motor. Twelve cats aged between 1 and 16 years were analyzed. Whole EOM tendons were immunostained using four different combinations of triple fluorescence labeling. Triple labeling included antibodies against choline acetyltransferase (ChAT), neurofilament, synaptophysin, and alpha-bungarotoxin. Preparations were examined by confocal laser scanning microscopy. ChAT-labeled EOMs were also analyzed by immunoelectron microscopy. Three-dimensional reconstructions were made of palisade endings. Palisade endings were found in the distal and proximal myotendinous regions of cat EOMs. These endings arose from thin nerve fibers coming from the muscle and extending into the tendon. There, the nerve fibers turned back 180 degrees to divide into terminal branches around the muscle fiber tips. Terminal branches established numerous contacts with the tendon attached to the muscle fiber tip and only a few contacts with the muscle fiber. Often, nerve fibers forming palisade endings on muscle fiber tips were observed to establish multiple motor contacts on muscle fibers outside palisade endings. Three-dimensional reconstructions depicted the complex morphology of the palisade endings. All nerve fibers supplying palisade endings stained positively for ChAT and neurofilament. All nerve terminals in palisade endings were ChAT and synaptophysin positive. Only neuromuscular contacts in palisade endings were positive for alpha-bungarotoxin, as well. This study provides evidence that palisade endings in cat EOMs have effector function. The findings may be of significance for strabismus surgery because palisade endings are also found in human EOMs.

Topographical relations between the posterior cricothyroid ligament and the inferior laryngeal nerve.

PubMed

Reidenbach, M M

1995-01-01

The posterior cricothyroid ligament and its topographic relation to the inferior laryngeal nerve were studied in 54 human adult male and female larynges. Fourteen specimens were impregnated with curable polymers and cut into 600-800 microns sections along different planes. Forty formalin-fixed hemi-larynges were dissected and various measurements were made. The posterior cricothyroid ligament provides a dorsal strengthening for the joint capsule of the cricothyroid joint. Its fibers spread in a fan-like manner from a small area of origin at the cricoid cartilage to a more extended area of attachment at the inferior thyroid cornu. The ligament consists of one (7.5%) to four (12.5%), in most cases of three (45.0%) or two (35.0%), individual parts oriented from mediocranial to latero-caudal. The inferior laryngeal nerve courses immediately dorsal to the ligament. In 60% it is covered by fibers of the posterior cricoarytenoid muscle, in the remaining 40% it is not. In this latter topographic situation there is almost no soft tissue interposed between the nerve and the hypopharynx. Therefore, the nerve may be exposed to pressure forces exerted from dorsally. It may be pushed against the unyielding posterior cricothyroid ligament and suffer functional or structural impairment. Probably, this mechanism may explain some of the laryngeal nerve lesions described in the literature after insertion of gastric tubes.

White matter of the brain

MedlinePlus

White matter is found in the deeper tissues of the brain (subcortical). It contains nerve fibers (axons), which are ... or covering called myelin. Myelin gives the white matter its color. It also protects the nerve fibers ...

Microstructural and ultrastructural assessment of inferior alveolar nerve damage following nerve lateralization and implant placement: an experimental study in rabbits.

PubMed

Yoshimoto, Marcelo; Watanabe, Il-sei; Martins, Marília T; Salles, Marcos B; Ten Eyck, Gary R; Coelho, Paulo G

2009-01-01

The present study assessed damage to the inferior alveolar nerve (IAN) following nerve lateralization and implant placement surgery through optical and transmission electron microscopy (TEM). IAN lateralization was performed in 16 adult female rabbits (Oryctolagus cuniculus). During the nerve lateralization procedure, one implant was placed through the mandibular canal, and the IAN was replaced in direct contact with the implant. The implant was placed in the right mandible, and the left side was used as a control (no surgical procedure). After 8 weeks, the animals were sacrificed and samples were prepared for optical and TEM analysis of IAN structural damage. Histomorphometric analysis was performed to determine the number and cross-sectional dimensions of nerve fascicles and myelin sheath thickness between experimental and control groups. The different parameters were compared by one-way analysis of variance at the 95% significance level. Alterations in the perineural and endoneural regions of the IAN, with higher degrees of vascularization, were observed in the experimental group. TEM showed that the majority of the myelinated nerve fibers were not affected in the experimental samples. No significant variation in the number of fascicles was observed, significantly larger fascicle height and width were observed in the control group, and significantly thicker myelin sheaths were observed in the experimental samples. IAN lateralization resulted in substantial degrees of tissue disorganization at the microstructural level because of the presence of edema. However, at the ultrastructural level, small amounts of fiber degeneration were observed.

Combined use of Doppler OCT and en face OCT functions for discrimination of an aneurysm in the lamina cribrosa from a disc hemorrhage.

PubMed

Holló, Gábor

2015-12-01

In addition to retinal nerve fiber layer thickness measurements, the recently introduced AngioVue optical coherence tomography (OCT) offers corresponding layer-by-layer Doppler OCT and en face OCT functions, for simultaneous evaluation of perfusion and structure of the optic nerve head. We investigated the clinical usefulness of combined use of Doppler and en face Fourier-domain OCT functions of the AngioVue Fourier-domain OCT for discrimination of a disc hemorrhage and a disc hemorrhage-like atypical vessel structure located deep in the lamina cribrosa. We present our findings with AngioVue OCT on a disc hemorrhage and a spatially related retinal nerve fiber layer bundle defect in a glaucomatous eye (case 1). Both alterations were detected on en face OCT images without any Doppler OCT signal. We also report on an aneurysm suggestive for a disc hemorrhage on clinical examination and disc photography in a treated ocular hypertensive eye (case 2). The aneurysm was within the lamina cribrosa tissue at the border of the cup and the neuroretinal rim. This vascular structure produced strong Doppler signals but no structurally detectable signs on the en face OCT images. Combined evaluation of corresponding Doppler OCT and en face OCT images enables ophthalmologists to easily separate true disc hemorrhages from disc hemorrhage-like deep vascular structures. This is of clinical significance in preventing unnecessary intensification of pressure-lowering treatment in glaucoma.

Prevalence of myelinated retinal nerve fibres in adult Indians: the Central India Eye and Medical Study.

PubMed

Nangia, Vinay; Jonas, Jost B; Khare, Anshu; Bhate, Karishma; Agarwal, Shubhra; Panda-Jonas, Songhomitra

2014-05-01

To determine the prevalence of myelinated retinal nerve fibers in the adult Indian population. The Central India Eye and Medical Study performed in rural Central India included 4711 participants aged 30+ years. The participants underwent a detailed ophthalmic and medical examination. Readable fundus photographs were available for 8645 eyes of 4485 (95.2%) subjects. Myelinated retinal nerve fibers were detected in 52 eyes (46 subjects) with a prevalence rate of 0.58±0.08 per 100 eyes [95% confidence interval (CI): 0.42, 0.74] and 1.03±0.15 per 100 subjects (95%CI: 0.73, 1.32). Prevalence of myelinated retinal nerve fibers was significantly associated hyperopic refractive error (p=0.008; OR: 1.31; 95%CI: 1.07, 1.59). It was not significantly associated with age (p=0.11), best corrected visual acuity (logMAR; p=0.33), intraocular pressure (p=0.09), amount of nuclear cataract (p=0.93), optic disc area (p=0.60), presence of glaucomatous optic nerve atrophy (p=0.62), and early age-related macular degeneration (p=0.53). Myelinated retinal nerve fibers are present in about 10 out of 1000 adult Indians in rural Central India, with a higher prevalence in hyperopic eyes. Prevalence of myelinated retinal nerve fibers was not associated with age, visual acuity, glaucoma and macular degeneration. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Feedback Information and Analysis for Microprocessor Controlled Muscle Stimulation.

DTIC Science & Technology

1981-12-01

muscle into fiberous tissue (Guyton, 1976) is not inevitable. The contractile power can be preserved and fiberous build-up reduced by electrical... isometric tension, velocity of contraction and coordination of movement, all with minimally induced muscle fatigue. The work of Petrofsky and Phillips... muscle . Each muscle fiber is innervated by only a single nerve, but a single motor nerve fiber branches to as many as thousands of different muscle

Automatic estimation of retinal nerve fiber bundle orientation in SD-OCT images using a structure-oriented smoothing filter

NASA Astrophysics Data System (ADS)

Ghafaryasl, Babak; Baart, Robert; de Boer, Johannes F.; Vermeer, Koenraad A.; van Vliet, Lucas J.

2017-02-01

Optical coherence tomography (OCT) yields high-resolution, three-dimensional images of the retina. A better understanding of retinal nerve fiber bundle (RNFB) trajectories in combination with visual field data may be used for future diagnosis and monitoring of glaucoma. However, manual tracing of these bundles is a tedious task. In this work, we present an automatic technique to estimate the orientation of RNFBs from volumetric OCT scans. Our method consists of several steps, starting from automatic segmentation of the RNFL. Then, a stack of en face images around the posterior nerve fiber layer interface was extracted. The image showing the best visibility of RNFB trajectories was selected for further processing. After denoising the selected en face image, a semblance structure-oriented filter was applied to probe the strength of local linear structure in a discrete set of orientations creating an orientation space. Gaussian filtering along the orientation axis in this space is used to find the dominant orientation. Next, a confidence map was created to supplement the estimated orientation. This confidence map was used as pixel weight in normalized convolution to regularize the semblance filter response after which a new orientation estimate can be obtained. Finally, after several iterations an orientation field corresponding to the strongest local orientation was obtained. The RNFB orientations of six macular scans from three subjects were estimated. For all scans, visual inspection shows a good agreement between the estimated orientation fields and the RNFB trajectories in the en face images. Additionally, a good correlation between the orientation fields of two scans of the same subject was observed. Our method was also applied to a larger field of view around the macula. Manual tracing of the RNFB trajectories shows a good agreement with the automatically obtained streamlines obtained by fiber tracking.

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

PubMed

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 the lengths of accessory nerve were long enough for neuritisation with phrenic nerve.

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

PubMed

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.

Immunohistochemical localization of FMRFamide-containing neurons and nerve fibers in the ganglia and the gonad wall of the scallop, Pecten maximus (L).

PubMed

Henry, M; Benlinmame, N; Belhsen, O K; Jule, Y; Mathieu, M

1995-02-01

The Phe-Met-Arg-Phe NH2 (FMRFamide)-like immunoreactivity was detected in neurons of the cerebro-pedal and visceral ganglia of the scallop Pecten maximus using immunohistochemical techniques. FMRFamide-like immunoreactivity was also found in nerve fibers localized in the connective tissue and the epithelial wall of the gonad. Electron microscopy study carried out on the gonads indicates the existence of numerous nerve fibers crossing the connective tissue; nerve terminals apposed to highly secretory cells were seen in the gonad wall. All in all, the present immunohistochemical and electron microscopic data suggest that FMRFamide might play an unusual secretagogue role in the gonad wall.

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

PubMed Central

Deng, Jiu-xu; Zhang, Dian-yin; Li, Ming; Weng, Jian; Kou, Yu-hui; Zhang, Pei-xun; Han, Na; Chen, Bo; Yin, Xiao-feng; Jiang, Bao-guo

2017-01-01

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification’ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect. PMID:29323049

Spontaneous laryngeal reinnervation following chronic recurrent laryngeal nerve injury.

PubMed

Kupfer, Robbi A; Old, Matthew O; Oh, Sang Su; Feldman, Eva L; Hogikyan, Norman D

2013-09-01

To enhance understanding of spontaneous laryngeal muscle reinnervation following severe recurrent laryngeal nerve injury by testing the hypotheses that 1) nerve fibers responsible for thyroarytenoid muscle reinnervation can originate from multiple sources and 2) superior laryngeal nerve is a source of reinnervation. Prospective, controlled, animal model. A combination of retrograde neuronal labeling techniques, immunohistochemistry, electromyography, and sequential observations of vocal fold mobility were employed in rat model of chronic recurrent laryngeal nerve injury. The current study details an initial set of experiments in sham surgical and denervated group animals and a subsequent set of experiments in a denervated group. At 3 months after recurrent laryngeal nerve resection, retrograde brainstem neuronal labeling identified cells in the characteristic superior laryngeal nerve cell body location as well as cells in a novel caudal location. Regrowth of neuron fibers across the site of previous recurrent laryngeal nerve resection was seen in 87% of examined animals in the denervated group. Electromyographic data support innervation by both the superior and recurrent laryngeal nerves following chronic recurrent laryngeal nerve injury. Following chronic recurrent laryngeal nerve injury in the rat, laryngeal innervation is demonstrated through the superior laryngeal nerve from cells both within and outside of the normal cluster of cells that supply the superior laryngeal nerve. The recurrent laryngeal nerve regenerates across a surgically created gap, but functional significance of regenerated nerve fibers is unclear. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Fascial structures and autonomic nerves in the female pelvis: a study using macroscopic slices and their corresponding histology.

PubMed

Tamakawa, Mitsuharu; Murakami, Gen; Takashima, Ken; Kato, Tomoyasu; Hareyama, Masato

2003-12-01

We investigated the topographical anatomy of the pelvic fasciae and autonomic nerves using macroscopic slices of five decalcified female pelves. The lateral aspect of the supravaginal cervix uteri and superior-most vagina issued abundant thick fiber bundles. These visceral fibrous tissues extended dorsolaterally, joined another fibrous tissue from the rectum (the actual lateral ligament of the rectum) and attached to the parietal fibrous tissues at and around the sciatic foramina (i.e. the sacrospinous ligament, thick fasciae of the coccygeus and piriformis and dorsal end of the covering fascia of the levator ani). The inferior or ventral vagina also issued thick fiber bundles communicating with the levator ani fascia. This connection between the vagina and levator fascia, when stretched, seemed to provide a macroscopic morphology called the arcus tendineus fasciae pelvis. The overall morphology of the visceroparietal fascial bridge exhibited a bilateral wing-like shape. The fascial bridge complex was adjacent but dorso-inferior to the internal iliac vascular sheath and located slightly ventral to the pelvic splanchnic nerve. However, the pelvic plexus and its peripheral branches were embedded in the fascial complex. The hypogastric nerve ran along and beneath the uterosacral peritoneal fold, which did not contain thick fibrous tissue. During surgery, in combination with the superficially located vascular sheath, the morphology of the visceroparietal fascial bridge and associated nerves seemed to be artificially changed and developed into the so-called cardinal, uterosacral, uterovesical and/or rectal lateral ligaments. The classical and original concepts of these pelvic fascial structures may need to be altered to adjust to these surgical observations.

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

PubMed Central

Leozappa, M.; Ciani, S.; Ferrari, T. Micelli

2011-01-01

Keratoconus associated with myelinated retinal nerve fibers is not frequent and the relationship between the two pathologies is difficult to explain, therefore studies and further investigation are required. The etiology of each condition may suggest the role of genetic factors. Follow-up is important to evaluate the progression of keratoconus and myelination. Here we describe the unusual coexistence of keratoconus and ipsilateral myelinated retinal nerve fiber layer and, for the first time, the corneal cross-linking treatment in this condition. PMID:21475609

The distribution of TRPV1 and TRPV2 in the rat pharynx.

PubMed

Sasaki, Rika; Sato, Tadasu; Yajima, Takehiro; Kano, Mitsuhiro; Suzuki, Toshihiko; Ichikawa, Hiroyuki

2013-07-01

Immunohistochemistry for two nociceptive transducers, the transient receptor potential cation channel subfamily V members 1 (TRPV1) and 2 (TRPV2), was performed on the pharynx and its adjacent regions. TRPV1-immunoreactivity (IR) was detected in nerve fibers beneath and within the epithelium and/or taste bud-like structure. In the pharynx, these nerve fibers were abundant in the naso-oral part and at the border region of naso-oral and laryngeal parts. They were also numerous on the laryngeal side of the epiglottis and in the soft palate. TRPV2-IR was expressed by dendritic cells in the pharynx and epiglottis, as well as in the root of the tongue and soft palate. These cells were located in the epithelium and lamina propria. TRPV2-immunoreactive (IR) dendritic cells were numerous in the naso-oral part of the pharynx, epiglottis, and tongue. Abundance of TRPV2-IR dendritic processes usually obscured the presence of TRPV2-IR nerve fibers in these portions. However, some TRPV2-IR nerve fibers could be observed in the epithelium of the soft palate. Retrograde tracing method also revealed that sensory neurons which innervate the pharynx or soft palate were abundant in the jugular-petrosal ganglion complex and relatively rare in the nodose ganglion. In the jugular-petrosal ganglion complex, TRPV1- and TRPV2-IR were expressed by one-third of pharyngeal and soft palate neurons. TRPV2-IR was also detected in 11.5 % pharyngeal and 30.9 % soft palate neurons in the complex. Coexpression of TRPV1 and CGRP was frequent among pharyngeal and soft palate neurons. The present study suggests that TRPV1- and TRPV2-IR jugular-petrosal neurons may be associated with the regulation of the swallowing reflex.

Retinal nerve fiber layer thickness measured with optical coherence tomography is related to visual function in glaucomatous eyes.

PubMed

El Beltagi, Tarek A; Bowd, Christopher; Boden, Catherine; Amini, Payam; Sample, Pamela A; Zangwill, Linda M; Weinreb, Robert N

2003-11-01

To determine the relationship between areas of glaucomatous retinal nerve fiber layer thinning identified by optical coherence tomography and areas of decreased visual field sensitivity identified by standard automated perimetry in glaucomatous eyes. Retrospective observational case series. Forty-three patients with glaucomatous optic neuropathy identified by optic disc stereo photographs and standard automated perimetry mean deviations >-8 dB were included. Participants were imaged with optical coherence tomography within 6 months of reliable standard automated perimetry testing. The location and number of optical coherence tomography clock hour retinal nerve fiber layer thickness measures outside normal limits were compared with the location and number of standard automated perimetry visual field zones outside normal limits. Further, the relationship between the deviation from normal optical coherence tomography-measured retinal nerve fiber layer thickness at each clock hour and the average pattern deviation in each visual field zone was examined by using linear regression (R(2)). The retinal nerve fiber layer areas most frequently outside normal limits were the inferior and inferior temporal regions. The least sensitive visual field zones were in the superior hemifield. Linear regression results (R(2)) showed that deviation from the normal retinal nerve fiber layer thickness at optical coherence tomography clock hour positions 6 o'clock, 7 o'clock, and 8 o'clock (inferior and inferior temporal) was best correlated with standard automated perimetry pattern deviation in visual field zones corresponding to the superior arcuate and nasal step regions (R(2) range, 0.34-0.57). These associations were much stronger than those between clock hour position 6 o'clock and the visual field zone corresponding to the inferior nasal step region (R(2) = 0.01). Localized retinal nerve fiber layer thinning, measured by optical coherence tomography, is topographically related to decreased localized standard automated perimetry sensitivity in glaucoma patients.

Auditory brainstem response latency in forward masking, a marker of sensory deficits in listeners with normal hearing thresholds

PubMed Central

Mehraei, Golbarg; Gallardo, Andreu Paredes; Shinn-Cunningham, Barbara G.; Dau, Torsten

2017-01-01

In rodent models, acoustic exposure too modest to elevate hearing thresholds can nonetheless cause auditory nerve fiber deafferentation, interfering with the coding of supra-threshold sound. Low-spontaneous rate nerve fibers, important for encoding acoustic information at supra-threshold levels and in noise, are more susceptible to degeneration than high-spontaneous rate fibers. The change in auditory brainstem response (ABR) wave-V latency with noise level has been shown to be associated with auditory nerve deafferentation. Here, we measured ABR in a forward masking paradigm and evaluated wave-V latency changes with increasing masker-to-probe intervals. In the same listeners, behavioral forward masking detection thresholds were measured. We hypothesized that 1) auditory nerve fiber deafferentation increases forward masking thresholds and increases wave-V latency and 2) a preferential loss of low-SR fibers results in a faster recovery of wave-V latency as the slow contribution of these fibers is reduced. Results showed that in young audiometrically normal listeners, a larger change in wave-V latency with increasing masker-to-probe interval was related to a greater effect of a preceding masker behaviorally. Further, the amount of wave-V latency change with masker-to-probe interval was positively correlated with the rate of change in forward masking detection thresholds. Although we cannot rule out central contributions, these findings are consistent with the hypothesis that auditory nerve fiber deafferentation occurs in humans and may predict how well individuals can hear in noisy environments. PMID:28159652

Multi-channel measurement for hetero-core optical fiber sensor by using CMOS camera

NASA Astrophysics Data System (ADS)

Koyama, Yuya; Nishiyama, Michiko; Watanabe, Kazuhiro

2015-07-01

Fiber optic smart structures have been developed over several decades by the recent fiber optic sensor technology. Optical intensity-based sensors, which use LD or LEDs, can be suitable for the monitor system to be simple and cost effective. In this paper, a novel fiber optic smart structure with human-like perception has been demonstrated by using intensity-based hetero-core optical fiber sensors system with the CMOS detector. The optical intensity from the hetero-core optical fiber bend sensor is obtained as luminance spots indicated by the optical power distributions. A number of optical intensity spots are simultaneously readout by taking a picture of luminance pattern. To recognize the state of fiber optic smart structure with the hetero-core optical fibers, the template matching process is employed with Sum of Absolute Differences (SAD). A fiber optic smart glove having five optic fiber nerves have been employed to monitor hand postures. Three kinds of hand postures have been recognized by means of the template matching process. A body posture monitoring has also been developed by placing the wearable hetero-core optical fiber bend sensors on the body segments. In order for the CMOS system to be a human brain-like, the luminescent spots in the obtained picture were arranged to make the pattern corresponding to the position of body segments. As a result, it was successfully demonstrated that the proposed fiber optic smart structure could recognize eight kinds of body postures. The developed system will give a capability of human brain-like processing to the existing fiber optic smart structures.

Histochemical discrimination of fibers in regenerating rat infraorbital nerve

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen.

PubMed

Choi, Stacey S; Zawadzki, Robert J; Greiner, Mark A; Werner, John S; Keltner, John L

2008-06-01

New technology allows more precise definition of structural alterations of all retinal layers although it has not been used previously in cases of optic disc drusen. Using Stratus and Fourier domain (FD) optical coherence tomography (OCT) and adaptive optics (AO) through a flood-illuminated fundus camera, we studied the retinas of a patient with long-standing optic disc drusen and acute visual loss at high altitude attributed to ischemic optic neuropathy. Stratus OCT and FD-OCT confirmed severe thinning of the retinal nerve fiber layer (RNFL). FD-OCT revealed disturbances in the photoreceptor layer heretofore not described in optic disc drusen patients. AO confirmed the FD-OCT findings in the photoreceptor layer and also showed reduced cone density at retinal locations associated with reduced visual sensitivity. Based on this study, changes occur not only in the RNFL but also in the photoreceptor layer in optic nerve drusen complicated by ischemic optic neuropathy. This is the first reported application of FD-OCT and the AO to this condition. Such new imaging technology may in the future allow monitoring of disease progression more precisely and accurately.

Muscle fiber types composition and type identified endplate morphology of forepaw intrinsic muscles in the rat.

PubMed

Pan, Feng; Mi, Jing-Yi; Zhang, Yan; Pan, Xiao-Yun; Rui, Yong-Jun

2016-06-01

The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.

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

NASA Astrophysics Data System (ADS)

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.

Noise-induced hearing loss alters the temporal dynamics of auditory-nerve responses

PubMed Central

Scheidt, Ryan E.; Kale, Sushrut; Heinz, Michael G.

2010-01-01

Auditory-nerve fibers demonstrate dynamic response properties in that they adapt to rapid changes in sound level, both at the onset and offset of a sound. These dynamic response properties affect temporal coding of stimulus modulations that are perceptually relevant for many sounds such as speech and music. Temporal dynamics have been well characterized in auditory-nerve fibers from normal-hearing animals, but little is known about the effects of sensorineural hearing loss on these dynamics. This study examined the effects of noise-induced hearing loss on the temporal dynamics in auditory-nerve fiber responses from anesthetized chinchillas. Post-stimulus time histograms were computed from responses to 50-ms tones presented at characteristic frequency and 30 dB above fiber threshold. Several response metrics related to temporal dynamics were computed from post-stimulus-time histograms and were compared between normal-hearing and noise-exposed animals. Results indicate that noise-exposed auditory-nerve fibers show significantly reduced response latency, increased onset response and percent adaptation, faster adaptation after onset, and slower recovery after offset. The decrease in response latency only occurred in noise-exposed fibers with significantly reduced frequency selectivity. These changes in temporal dynamics have important implications for temporal envelope coding in hearing-impaired ears, as well as for the design of dynamic compression algorithms for hearing aids. PMID:20696230

Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy.

PubMed

Srinivasan, Sangeetha; Dehghani, Cirous; Pritchard, Nicola; Edwards, Katie; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2017-12-01

To examine the neuronal structural integrity of cornea and retina as markers for neuronal degeneration in nonproliferative diabetic retinopathy (NPDR). Participants were recruited from the broader Brisbane community, Queensland, Australia. Two hundred forty-one participants (187 with diabetes and 54 nondiabetic controls) were examined. Diabetic retinopathy (DR) was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), corneal nerve fiber tortuosity (CNFT), full retinal thickness, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), focal (FLV) and global loss volumes (GLV), hemoglobin A1c (HbA1c), nephropathy, neuropathy, and cardiovascular measures were examined. The central zone (P = 0.174), parafoveal thickness (P = 0.090), perifovea (P = 0.592), RNFL (P = 0.866), GCC (P = 0.798), and GCC GLV (P = 0.338) did not differ significantly between the groups. In comparison to the control group, those with very mild NPDR and those with mild NPDR had significantly higher focal loss in GCC volume (P = 0.036). CNFL was significantly lower in those with mild NPDR (P = 0.004) in comparison to the control group and those with no DR. The CNBD (P = 0.094) and CNFT (P = 0.458) did not differ between the groups. Both corneal and retinal neuronal degeneration may occur in early stages of diabetic retinopathy. Further studies are required to examine these potential markers for neuronal degeneration in the absence of clinical signs of DR.

[NADPH-diaphorase activity in digestive system of gastropod molluscs Achatina fulica and Littorina littorea].

PubMed

Zaĭtseva, O V; Kuznetsova, T V; Markosova, T G

2009-01-01

Localization and peculiarities of NO-ergic elements were studied for he first time throughout the entire length of digestive tract of the marine gastropod mollusc Achatina fulica (Prosobranchia) and the terrestrial molusc Littorina littorea (Pulmonata) by using histochemical method of detection of NADPH-diaphorase (NADPHd). NO-ergic cells and fibers were revealed in all parts of the mollusc digestive tract beginning from pharynx. An intensive NADPHd activity was found in many intraepithelial cells of the open type and in their processes in intra- and subepithelial nerve plexuses, single subepithelial neurons, granular connective tissue cells, and numerous nerve fibers among muscle elements of he digestive tract wall as well as in nerves innervating the tract. NADPHd was also present in receptor cells of he oral area and in the central A. fulica ganglia participating in innervation of the digestive tract. The digestive tract NO-ergic system ofA. fulica has a more complex organization that that of L. littorea. In the A. fulica pharynx, stomach, and midgut, directly beneath epithelium, there is revealed a complex system of glomerular structures formed by thin NADPHd-positive nerve fibers coming from the side of epithelium. More superficially under the main groups of muscle elements, small agglomerations of NADPHd-positive neurons are seen, which could be considered as primitive, non-formed microganglia. Peculiarities of distribution and a possible functional role of NO-ergic elements in the digestive tract of molluscs are discussed as compared with other invertebrate and vertebrate animals.

5-HT3A -driven green fluorescent protein delineates gustatory fibers innervating sour-responsive taste cells: A labeled line for sour taste?

PubMed

Stratford, J M; Larson, E D; Yang, R; Salcedo, E; Finger, T E

2017-07-01

Taste buds contain multiple cell types with each type expressing receptors and transduction components for a subset of taste qualities. The sour sensing cells, Type III cells, release serotonin (5-HT) in response to the presence of sour (acidic) tastants and this released 5-HT activates 5-HT 3 receptors on the gustatory nerves. We show here, using 5-HT 3A GFP mice, that 5-HT 3 -expressing nerve fibers preferentially contact and receive synaptic contact from Type III taste cells. Further, these 5-HT 3 -expressing nerve fibers terminate in a restricted central-lateral portion of the nucleus of the solitary tract (nTS)-the same area that shows increased c-Fos expression upon presentation of a sour tastant (30 mM citric acid). This acid stimulation also evokes c-Fos in the laterally adjacent mediodorsal spinal trigeminal nucleus (DMSp5), but this trigeminal activation is not associated with the presence of 5-HT 3 -expressing nerve fibers as it is in the nTS. Rather, the neuronal activation in the trigeminal complex likely is attributable to direct depolarization of acid-sensitive trigeminal nerve fibers, for example, polymodal nociceptors, rather than through taste buds. Taken together, these findings suggest that transmission of sour taste information involves communication between Type III taste cells and 5-HT 3 -expressing afferent nerve fibers that project to a restricted portion of the nTS consistent with a crude mapping of taste quality information in the primary gustatory nucleus. © 2017 Wiley Periodicals, Inc.

Differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

PubMed

Tong, Ling-Ling; Ding, You-Quan; Jing, Hong-Bo; Li, Xuan-Yang; Qi, Jian-Guo

2015-05-06

Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that Aα fiber-mediated motor function was successfully recovered in both male and female rats. Aδ fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, Aβ and Aδ fibers incompletely remyelinated in male, but not female rats, whereas Aα fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

Real-time needle guidance with photoacoustic and laser-generated ultrasound probes

NASA Astrophysics Data System (ADS)

Colchester, Richard J.; Mosse, Charles A.; Nikitichev, Daniil I.; Zhang, Edward Z.; West, Simeon; Beard, Paul C.; Papakonstantinou, Ioannis; Desjardins, Adrien E.

2015-03-01

Detection of tissue structures such as nerves and blood vessels is of critical importance during many needle-based minimally invasive procedures. For instance, unintentional injections into arteries can lead to strokes or cardiotoxicity during interventional pain management procedures that involve injections in the vicinity of nerves. Reliable detection with current external imaging systems remains elusive. Optical generation and reception of ultrasound allow for depth-resolved sensing and they can be performed with optical fibers that are positioned within needles used in clinical practice. The needle probe developed in this study comprised separate optical fibers for generating and receiving ultrasound. Photoacoustic generation of ultrasound was performed on the distal end face of an optical fiber by coating it with an optically absorbing material. Ultrasound reception was performed using a high-finesse Fabry-Pérot cavity. The sensor data was displayed as an M-mode image with a real-time interface. Imaging was performed on a biological tissue phantom.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry

PubMed Central

Hömberg, Lisann; Eter, Nicole

2017-01-01

Purpose To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). Materials and Methods 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3–6) or the control group (group B: RNFL score 0–2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Results Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. Conclusions In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP. PMID:29119021

NEURAL ORGANIZATION OF SENSORY INFORMATIONS FOR TASTE,

DTIC Science & Technology

TASTE , ELECTROPHYSIOLOGY), (*NERVES, *TONGUE), NERVE CELLS, NERVE IMPULSES, PHYSIOLOGY, NERVOUS SYSTEM, STIMULATION(PHYSIOLOGY), NERVE FIBERS, RATS...HAMSTERS, STIMULATION(PHYSIOLOGY), PERCEPTION, COOLING, BEHAVIOR, PSYCHOPHYSIOLOGY, TEMPERATURE, THRESHOLDS(PHYSIOLOGY), CHEMORECEPTORS , STATISTICAL ANALYSIS, JAPAN

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

PubMed

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.

Changes in Structure, Interstitial Cajal-like Cells and Apoptosis of Smooth Muscle Cells in Congenital Ureteropelvic Junction Obstruction

PubMed Central

Mehrazma, Mitra; Tanzifi, Parin; Rakhshani, Naser

2014-01-01

Objective: The goal of this study is to evaluate some structural changes in muscular, collagenous and neural components as well as expression of Cajal-like cells and apoptosis of smooth muscle cells in congenital ureteropelvic junction obstruction (UPJO). Methods: Tissue specimens were obtained from 25 patients with UPJO and compared with normal ureteropelvic junction regions of 19 autopsies. In paraffin embedded sections the amount of Cajal-like cells, density of nerve fibers and smooth muscle cell apoptosis (using immunohistochemical staining) were determined. Collagen deposition and muscular components were stained by Trichrome-Masson staining and evaluated by image analysis techniques. Arrangement of muscular bundles was also evaluated qualitatively. Findings : The number of Cajal-like cells was significantly lower in patients than in controls. The apoptotic score and mean number of nerve fibers were not statistically different for the two groups. Arrangement of muscular fibers was more irregular in patients than in controls (P<0.001). Collagen deposition was significantly higher in patients than in controls (P<0.001). The mean amount of muscular component was lower in patients than in normal ones. (P= 0.09) Conclusion: We found significant pathologic changes in congenital ureteropelvic junction obstruction such as decrease in Cajal-like cells, increase in collagen deposition and irregular arrangement of muscle fibers. PMID:25793054

Variable expression of GFP in different populations of peripheral cholinergic neurons of ChATBAC-eGFP transgenic mice.

PubMed

Brown, T Christopher; Bond, Cherie E; Hoover, Donald B

2018-03-01

Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed transgenic mice that express enhanced green fluorescent protein (GFP) directed by the promoter for choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme. Although, it was reported that these mice express GFP in all cholinergic neurons and non-neuronal cholinergic cells, we could not detect GFP in cardiac cholinergic nerves in preliminary experiments. Our goals for this study were to confirm our initial observation and perform a qualitative screen of other representative autonomic structures for the presences of GFP in cholinergic innervation of effector tissues. We evaluated GFP fluorescence of intact, unfixed tissues and the cellular localization of GFP and vesicular acetylcholine transporter (VAChT), a specific cholinergic marker, in tissue sections and intestinal whole mounts. Our experiments identified two major tissues where cholinergic neurons and/or nerve fibers lacked GFP: 1) most cholinergic neurons of the intrinsic cardiac ganglia and all cholinergic nerve fibers in the heart and 2) most cholinergic nerve fibers innervating airway smooth muscle. Most cholinergic neurons in airway ganglia stained for GFP. Cholinergic systems in the bladder and intestines were fully delineated by GFP staining. GFP labeling of input to ganglia with long preganglionic projections (vagal) was sparse or weak, while that to ganglia with short preganglionic projections (spinal) was strong. Total absence of GFP might be due to splicing out of the GFP gene. Lack of GFP in nerve projections from GFP-positive cell bodies might reflect a transport deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

A multiscale approach for the reconstruction of the fiber architecture of the human brain based on 3D-PLI

PubMed Central

Reckfort, Julia; Wiese, Hendrik; Pietrzyk, Uwe; Zilles, Karl; Amunts, Katrin; Axer, Markus

2015-01-01

Structural connectivity of the brain can be conceptionalized as a multiscale organization. The present study is built on 3D-Polarized Light Imaging (3D-PLI), a neuroimaging technique targeting the reconstruction of nerve fiber orientations and therefore contributing to the analysis of brain connectivity. Spatial orientations of the fibers are derived from birefringence measurements of unstained histological sections that are interpreted by means of a voxel-based analysis. This implies that a single fiber orientation vector is obtained for each voxel, which reflects the net effect of all comprised fibers. We have utilized two polarimetric setups providing an object space resolution of 1.3 μm/px (microscopic setup) and 64 μm/px (macroscopic setup) to carry out 3D-PLI and retrieve fiber orientations of the same tissue samples, but at complementary voxel sizes (i.e., scales). The present study identifies the main sources which cause a discrepancy of the measured fiber orientations observed when measuring the same sample with the two polarimetric systems. As such sources the differing optical resolutions and diverging retardances of the implemented waveplates were identified. A methodology was implemented that enables the compensation of measured different systems' responses to the same birefringent sample. This opens up new ways to conduct multiscale analysis in brains by means of 3D-PLI and to provide a reliable basis for the transition between different scales of the nerve fiber architecture. PMID:26388744

Fabrication and characterization of biomimetic multichanneled crosslinked-urethane-doped polyester tissue engineered nerve guides.

PubMed

Tran, Richard T; Choy, Wai Man; Cao, Hung; Qattan, Ibrahim; Chiao, Jung-Chih; Ip, Wing Yuk; Yeung, Kelvin Wai Kwok; Yang, Jian

2014-08-01

Biomimetic scaffolds that replicate the native architecture and mechanical properties of target tissues have been recently shown to be a very promising strategy to guide cellular growth and facilitate tissue regeneration. In this study, porous, soft, and elastic crosslinked urethane-doped polyester (CUPE) tissue engineered nerve guides were fabricated with multiple longitudinally oriented channels and an external non-porous sheath to mimic the native endoneurial microtubular and epineurium structure, respectively. The fabrication technique described herein is highly adaptable and allows for fine control over the resulting nerve guide architecture in terms of channel number, channel diameter, porosity, and mechanical properties. Biomimetic multichanneled CUPE guides were fabricated with various channel numbers and displayed an ultimate peak stress of 1.38 ± 0.22 MPa with a corresponding elongation at break of 122.76 ± 42.17%, which were comparable to that of native nerve tissue. The CUPE nerve guides were also evaluated in vivo for the repair of a 1 cm rat sciatic nerve defect. Although histological evaluations revealed collapse of the inner structure from CUPE TENGs, the CUPE nerve guides displayed fiber populations and densities comparable with nerve autograft controls after 8 weeks of implantation. These studies are the first report of a CUPE-based biomimetic multichanneled nerve guide and warrant future studies towards optimization of the channel geometry for use in neural tissue engineering. © 2013 Wiley Periodicals, Inc.

The visceromotor and somatic afferent nerves of the penis.

PubMed

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.

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

PubMed

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.

MELANOPHORE BANDS AND AREAS DUE TO NERVE CUTTING, IN RELATION TO THE PROTRACTED ACTIVITY OF NERVES

PubMed Central

Parker, G. H.

1941-01-01

1. When appropriate chromatic nerves are cut caudal bands, cephalic areas, and the pelvic fins of the catfish Ameiurus darken. In pale fishes all these areas will sooner or later blanch. By recutting their nerves all such blanched areas will darken again. 2. These observations show that the darkening of caudal bands, areas, and fins on cutting their nerves is not due to paralysis (Brücke), to the obstruction of central influences such as inhibition (Zoond and Eyre), nor to vasomotor disturbances (Hogben), but to activities emanating from the cut itself. 3. The chief agents concerned with the color changes in Ameiurus are three: intermedin from the pituitary gland, acetylcholine from the dispersing nerves (cholinergic fibers), and adrenalin from the concentrating nerves (adrenergic fibers). The first two darken the fish; the third blanches it. In darkening the dispersing nerves appear to initiate the process and to be followed and substantially supplemented by intermedin. 4. Caudal bands blanch by lateral invasion, cephalic areas by lateral invasion and internal disintegration, and pelvic fins by a uniform process of general loss of tint equivalent to internal disintegration. 5. Adrenalin may be carried in such an oil as olive oil and may therefore act as a lipohumor; it is soluble in water and hence may act as a hydrohumor. In lateral invasion (caudal bands, cephalic areas) it probably acts as a lipohumor and in internal disintegration (cephalic areas, pelvic fins) it probably plays the part of a hydrohumor. 6. The duration of the activity of dispersing nerves after they had been cut was tested by means of the oscillograph, by anesthetizing blocks, and by cold-blocks. The nerves of Ameiurus proved to be unsatisfactory for oscillograph tests. An anesthetizing block, magnesium sulfate, is only partly satisfactory. A cold-block, 0°C., is successful to a limited degree. 7. By means of a cold-block it can be shown that dispersing autonomic nerve fibers in Ameiurus can continue in activity for at least 6½ hours. It is not known how much longer they may remain active. So far as the duration of their activity is concerned dispersing nerve fibers in this fish are unlike other types of nerve fibers usually studied. PMID:19873231

NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy

PubMed Central

Van Acker, Nathalie; Ragé, Michael; Vermeirsch, Hilde; Schrijvers, Dorien; Nuydens, Rony; Byttebier, Geert; Timmers, Maarten; De Schepper, Stefanie; Streffer, Johannes; Andries, Luc; Plaghki, Léon; Cras, Patrick; Meert, Theo

2016-01-01

The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes. PMID:27598321

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

PubMed Central

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

2018-01-01

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. PMID:28600222

Ultrastructural and molecular biologic comparison of classic proprioceptors and palisade endings in sheep extraocular muscles.

PubMed

Rungaldier, Stefanie; Heiligenbrunner, Stefan; Mayer, Regina; Hanefl-Krivanek, Christiane; Lipowec, Marietta; Streicher, Johannes; Blumer, Roland

2009-12-01

To analyze and compare the structural and molecular features of classic proprioceptors like muscle spindles and Golgi tendon organs (GTOs) and putative proprioceptors (palisade endings) in sheep extraocular muscle (EOMs). The EOMs of four sheep were analyzed. Frozen sections or wholemount preparations of the samples were immunohistochemically labeled and analyzed by confocal laser scanning microscopy. Triple labeling with different combinations of antibodies against neurofilament, synaptophysin, and choline acetyltransferase (ChAT), as well as alpha-bungarotoxin and phalloidin, was performed. Microscopic anatomy of the nerve end organs was analyzed by transmission electron microscopy. The microscopic anatomy demonstrated that muscle spindles and GTOs had a perineural capsule and palisade endings a connective tissue capsule. Sensory nerve terminals in muscle spindles and GTOs contained only a few vesicles, whereas palisade nerve terminals were full of clear vesicles. Likewise, motor terminals in the muscle spindles' polar regions were full of clear vesicles. Immunohistochemistry showed that sensory nerve fibers as well as their sensory nerve terminals in muscle spindles and GTOs were ChAT-negative. Palisade endings were supplied by ChAT-positive nerve fibers, and the palisade complexes including palisade nerve terminals were also ChAT-immunoreactive. Motor terminals in muscle spindles were ChAT and alpha-bungarotoxin positive. The present study demonstrated in sheep EOMs that palisade endings are innervated by cholinergic axons exhibiting characteristics typical of motoneurons, whereas muscle spindles (except the polar regions) and GTOs are supplied by noncholinergic axons. These results raise the question of whether palisade endings are candidates for proprioceptors in EOMs.

Ultrastructural and molecular biologic comparison of classical proprioceptors and palisade endings in sheep extraocular muscles

PubMed Central

RUNGALDIER, Stefanie; HEILIGENBRUNNER, Stefan; MAYER, Regina; HANEFL-KRIVANEK, Christiane; LIPOWEC, Marietta; STREICHER, Johannes; BLUMER, Roland

2016-01-01

Purpose To analyze and compare the structural and molecular features of classical proprioceptors like muscle spindles and Golgi tendon organs (GTOs) and putative proprioceptors (palisade endings) in sheep extraocular muscle (EOMs). Methods The EOMs of four sheep were analyzed. Frozen sections or whole mount preparations of the samples were immunohistochemically labeled and analyzed by confocal laser scanning microscopy. Triple labeling with different combinations of antibodies against neurofilament, synaptophysin and choline acetyltransferase (ChAT) as well as α-bungarotoxin and phalloidin was performed. Microscopic anatomy of the nerve end organs was analyzed by transmission electron microscopy. Results The microscopic anatomy demonstrated that muscle spindles and GTOs had a perineural capsule and palisade endings a connective tissue capsule. Sensory nerve terminals in muscle spindles and GTOs contained only few vesicles whereas palisade nerve terminals were full of clear vesicles. Likewise, motor terminals in the muscle spindles’ polar regions were full of clear vesicles. Immunohistochemistry showed that sensory nerve fibers as well as their sensory nerve terminals in muscle spindles and GTOs were ChAT-negative. Palisade endings were supplied by ChAT-positive nerve fibers and the palisade complexes including palisade nerve terminals were also ChAT-immunoreactive. Motor terminals in muscle spindles were ChAT and α-bungarotoxin -positive. Conclusions The present study demonstrated in sheep EOMs that palisade endings are innervated by cholinergic axons exhibiting characteristics typical for motoneurons whereas muscle spindles (except the polar regions) and GTOs are supplied by non-cholinergic axons. These results question whether palisade endings are candidates for proprioceptors in EOMs. PMID:19553627

Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

PubMed

Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

2011-09-01

The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. © 2011 Peripheral Nerve Society.

Optic Nerve Disorders

MedlinePlus

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 ...

Shock wave treatment improves nerve regeneration in the rat.

PubMed

Mense, Siegfried; Hoheisel, Ulrich

2013-05-01

The aims of the experiments were to: (1) determine whether low-energy shock wave treatment accelerates the recovery of muscle sensitivity and functionality after a nerve lesion; and (2) assess the effect of shock waves on the regeneration of injured nerve fibers. After compression of a muscle nerve in rats the effects of shock wave treatment on the sequelae of the lesion were tested. In non-anesthetized animals, pressure pain thresholds and exploratory activity were determined. The influence of the treatment on the distance of nerve regeneration was studied in immunohistochemical experiments. Both behavioral and immunohistochemical data show that shock wave treatment accelerates the recovery of muscle sensitivity and functionality and promotes regeneration of injured nerve fibers. Treatment with focused shock waves induces an improvement of nerve regeneration in a rodent model of nerve compression. Copyright © 2012 Wiley Periodicals, Inc.

Palisade endings in extraocular muscles of the monkey are immunoreactive for choline acetyltransferase and vesicular acetylcholine transporter.

PubMed

Konakci, Kadriye Zeynep; Streicher, Johannes; Hoetzenecker, Wolfram; Haberl, Ines; Blumer, Michael Josef Franz; Wieczorek, Grazyna; Meingassner, Josef Gottfried; Paal, Szabolcs Levente; Holzinger, Daniel; Lukas, Julius-Robert; Blumer, Roland

2005-12-01

To analyze palisade endings in extraocular muscles (EOMs) of a primate species and to examine our previous findings in cat that palisade endings are putative effector organs. Eleven monkeys (Macaca fascicularis) of both sexes, between 4 and 6 years of age were analyzed. Whole EOM myotendons were immunostained with four combinations of triple-fluorescent labeling and examined by confocal laser scanning microscopy. Labeling included antibodies against choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), neurofilament, and synaptophysin. Muscle fibers were counterstained with phalloidin. Palisade endings were observed in all monkey EOMs. Nerve fibers extended from the muscle into the tendon and looped back to divide into a terminal arborization (palisade ending) around a single muscle fiber tip. In approximately 30% of the cases, nerve fibers supplying palisade endings often established motor terminals outside the palisade complex. Nerve fibers forming palisade endings were ChAT-neurofilament positive. Axonal branches of palisade endings were ChAT-neurofilament positive as well. All palisade nerve terminals exhibited ChAT-synaptophysin immunoreactivity. Within the palisade complex, palisade nerve terminals exhibited VAChT immunoreactivity. All palisade nerve terminals were VAChT-synaptophysin immunoreactive. The results confirm that in the monkey, palisade endings contain acetylcholine and are therefore most likely effector organs. Palisade endings are also present in human EOMs and because of their location at the myotendinous junction, these organs are of crucial interest for strabismus surgery.

Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis.

PubMed

Takeuchi, Arisa; Koga, Kaori; Miyashita, Mariko; Makabe, Tomoko; Sue, Fusako; Harada, Miyuki; Hirata, Tetsuya; Hirota, Yasushi; Fujii, Tomoyuki; Osuga, Yutaka

2016-12-01

To evaluate the in vivo effect of dienogest on proliferation, apoptosis, aromatase expression, vascular density, nerve growth factor (NGF) expression and nerve fiber density in human adenomyosis tissue. Twelve women who underwent hysterectomy for adenomyosis were enrolled. Six patients received dienogest treatment prior to hysterectomy (dienogest group), and age-matched six patients who had not received any hormonal treatment for ≥3 months before surgery (control group). Cell proliferation, vascular and nerve fiber density in adenomyosis tissue were evaluated by staining for Ki67, von Willebrand factor and PGP9.5, respectively. Apoptosis was detected using the TUNEL assay. The expression aromatase and NGF were evaluated by staining for corresponding antibodies. The proportion of Ki67 positive epithelial cells was significantly lower in samples from dienogest-treated patients in comparison with controls (p<0.05). The density of blood vessels in adenomyosis was marginally lower in the dienogest group in comparison with controls but statistical significance was not reached (p=0.07). The intensity of NGF expression and the density of nerve fibers were significantly lower in the dienogest group compared with controls (p<0.05 for both). This study demonstrates that adenomyosis, taken from patients treated with dienogest, shows remarkable histological features, such as reductions in proliferation, NGF expression and nerve fiber density. These findings indicate the impact of dienogest on local histological events, and explains its therapeutic effect on adenomyosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema

PubMed Central

Chiang, Chia-Wen; Wang, Yong; Sun, Peng; Lin, Tsen-Hsuan; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA), increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice. PMID:25017446

Anatomic assessment of sympathetic peri-arterial renal nerves in man.

PubMed

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 < 0.001). The mean number of nerves in the ventral region (11.0 ± 3.5 per section) was greater compared with the dorsal region (6.2 ± 3.0 per section) (p < 0.001). Efferent nerve fibers were predominant (tyrosine hydroxylase/calcitonin gene-related peptide ratio 25.1 ± 33.4; p < 0.0001). Nerve anatomy in hypertensive patients was not considerably different compared with nonhypertensive patients. The density of peri-arterial 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.

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

PubMed

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.

Spinal cord projections of the rat main forelimb nerves, studied by transganglionic transport of WGA-HRP and by the disappearance of acid phosphatase.

PubMed

Castro-Lopes, J M; Coimbra, A

1991-03-01

The spinal cord projections of the 3 main forelimb nerves-median, radial and ulnar, were studied in the rat dorsal horn with transganglionic transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP), or using the disappearance of fluoride resistant acid phosphatase (FRAP) after nerve section. The projection patterns in lamina II were similar following the two procedures. The median and the radial nerve fibers projected to the medial and the intermediate thirds, respectively, of the dorsal horn lamina II in spinal cord segments C4-C8. The ulnar nerve projected to segments C6-C8 between the areas occupied by the other two nerves. The FRAP method also showed that the lateral part of lamina II, which was not filled by radial nerve fibers, received the projections from the dorsal cutaneous branches of cervical spinal nerves. In addition, FRAP disappeared from the medial end of segment T1 after skin incisions extending from the medial brachium to the axilla, which seemed due to severance of the cutaneous branchlets of the lateral anterior thoracic nerve. The FRAP procedure is thus sensitive enough to detect fibers in lamina II arising from small peripheral nerves, and may be used as an alternative to the anterograde tracing methods whenever there are no overlapping projections.

Virtual Instrumentation for a Fiber-Optics-Based Artificial Nerve

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

Stochastic information transfer from cochlear implant electrodes to auditory nerve fibers

NASA Astrophysics Data System (ADS)

Gao, Xiao; Grayden, David B.; McDonnell, Mark D.

2014-08-01

Cochlear implants, also called bionic ears, are implanted neural prostheses that can restore lost human hearing function by direct electrical stimulation of auditory nerve fibers. Previously, an information-theoretic framework for numerically estimating the optimal number of electrodes in cochlear implants has been devised. This approach relies on a model of stochastic action potential generation and a discrete memoryless channel model of the interface between the array of electrodes and the auditory nerve fibers. Using these models, the stochastic information transfer from cochlear implant electrodes to auditory nerve fibers is estimated from the mutual information between channel inputs (the locations of electrodes) and channel outputs (the set of electrode-activated nerve fibers). Here we describe a revised model of the channel output in the framework that avoids the side effects caused by an "ambiguity state" in the original model and also makes fewer assumptions about perceptual processing in the brain. A detailed comparison of how different assumptions on fibers and current spread modes impact on the information transfer in the original model and in the revised model is presented. We also mathematically derive an upper bound on the mutual information in the revised model, which becomes tighter as the number of electrodes increases. We found that the revised model leads to a significantly larger maximum mutual information and corresponding number of electrodes compared with the original model and conclude that the assumptions made in this part of the modeling framework are crucial to the model's overall utility.

Effects of sensorineural hearing loss on temporal coding of narrowband and broadband signals in the auditory periphery

PubMed Central

Henry, Kenneth S.; Heinz, Michael G.

2013-01-01

People with sensorineural hearing loss have substantial difficulty understanding speech under degraded listening conditions. Behavioral studies suggest that this difficulty may be caused by changes in auditory processing of the rapidly-varying temporal fine structure (TFS) of acoustic signals. In this paper, we review the presently known effects of sensorineural hearing loss on processing of TFS and slower envelope modulations in the peripheral auditory system of mammals. Cochlear damage has relatively subtle effects on phase locking by auditory-nerve fibers to the temporal structure of narrowband signals under quiet conditions. In background noise, however, sensorineural loss does substantially reduce phase locking to the TFS of pure-tone stimuli. For auditory processing of broadband stimuli, sensorineural hearing loss has been shown to severely alter the neural representation of temporal information along the tonotopic axis of the cochlea. Notably, auditory-nerve fibers innervating the high-frequency part of the cochlea grow increasingly responsive to low-frequency TFS information and less responsive to temporal information near their characteristic frequency (CF). Cochlear damage also increases the correlation of the response to TFS across fibers of varying CF, decreases the traveling-wave delay between TFS responses of fibers with different CFs, and can increase the range of temporal modulation frequencies encoded in the periphery for broadband sounds. Weaker neural coding of temporal structure in background noise and degraded coding of broadband signals along the tonotopic axis of the cochlea are expected to contribute considerably to speech perception problems in people with sensorineural hearing loss. PMID:23376018

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

PubMed

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.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

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

PubMed

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 < 0.05). The superior peripapillary retinal nerve fiber layer thickness was 112.0 ± 13.2 in the patient group and 120.0 ± 14.7 μm in the control group (P < 0.02). According to the results of both measurements, the peripapillary retinal nerve fiber layer thickness was significantly lower in the patient group. Neither color vision loss nor visual field examination abnormality could be documented. According to the optical coherence tomography measurements, the average and superior peripapillary retinal nerve fiber layer thicknesses were thinner in patients with 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.

Are Human Peripheral Nerves Sensitive to X-Ray Imaging?

PubMed Central

Scopel, Jonas Francisco; de Souza Queiroz, Luciano; O’Dowd, Francis Pierce; Júnior, Marcondes Cavalcante França; Nucci, Anamarli; Hönnicke, Marcelo Gonçalves

2015-01-01

Diagnostic imaging techniques play an important role in assessing the exact location, cause, and extent of a nerve lesion, thus allowing clinicians to diagnose and manage more effectively a variety of pathological conditions, such as entrapment syndromes, traumatic injuries, and space-occupying lesions. Ultrasound and nuclear magnetic resonance imaging are becoming useful methods for this purpose, but they still lack spatial resolution. In this regard, recent phase contrast x-ray imaging experiments of peripheral nerve allowed the visualization of each nerve fiber surrounded by its myelin sheath as clearly as optical microscopy. In the present study, we attempted to produce high-resolution x-ray phase contrast images of a human sciatic nerve by using synchrotron radiation propagation-based imaging. The images showed high contrast and high spatial resolution, allowing clear identification of each fascicle structure and surrounding connective tissue. The outstanding result is the detection of such structures by phase contrast x-ray tomography of a thick human sciatic nerve section. This may further enable the identification of diverse pathological patterns, such as Wallerian degeneration, hypertrophic neuropathy, inflammatory infiltration, leprosy neuropathy and amyloid deposits. To the best of our knowledge, this is the first successful phase contrast x-ray imaging experiment of a human peripheral nerve sample. Our long-term goal is to develop peripheral nerve imaging methods that could supersede biopsy procedures. PMID:25757086

Localization of cholinergic innervation and neurturin receptors in adult mouse heart and expression of the neurturin gene.

PubMed

Mabe, Abigail M; Hoard, Jennifer L; Duffourc, Michelle M; Hoover, Donald B

2006-10-01

Neurturin (NRTN) is a neurotrophic factor required during development for normal cholinergic innervation of the heart, but whether NRTN continues to function in the adult heart is unknown. We have therefore evaluated NRTN expression in adult mouse heart and the association of NRTN receptors with intracardiac cholinergic neurons and nerve fibers. Mapping the regional distribution and density of cholinergic nerves in mouse heart was an integral part of this goal. Analysis of RNA from adult C57BL/6 mouse hearts demonstrated NRTN expression in atrial and ventricular tissue. Virtually all neurons in the cardiac parasympathetic ganglia exhibited the cholinergic phenotype, and over 90% of these cells contained both components of the NRTN receptor, Ret tyrosine kinase and GDNF family receptor alpha2 (GFRalpha2). Cholinergic nerve fibers, identified by labeling for the high affinity choline transporter, were abundant in the sinus and atrioventricular nodes, ventricular conducting system, interatrial septum, and much of the right atrium, but less abundant in the left atrium. The right ventricular myocardium contained a low density of cholinergic nerves, which were sparse in other regions of the working ventricular myocardium. Some cholinergic nerves were also associated with coronary vessels. GFRalpha2 was present in most cholinergic nerve fibers and in Schwann cells and their processes throughout the heart. Some cholinergic nerve fibers, such as those in the sinus node, also exhibited Ret immunoreactivity. These findings provide the first detailed mapping of cholinergic nerves in mouse heart and suggest that the neurotrophic influence of NRTN on cardiac cholinergic innervation continues in mature animals.

Challenges for Nerve Repair Using Chitosan-Siloxane Hybrid Porous Scaffolds

PubMed Central

Shirosaki, Yuki; Hayakawa, Satoshi; Osaka, Akiyoshi; Lopes, Maria A.; Santos, José D.; Geuna, Stefano; Mauricio, Ana C.

2014-01-01

The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton's jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration. PMID:25054129

Deep-tissue two-photon imaging in brain and peripheral nerve with a compact high-pulse energy ytterbium fiber laser

NASA Astrophysics Data System (ADS)

Fontaine, Arjun K.; Kirchner, Matthew S.; Caldwell, John H.; Weir, Richard F.; Gibson, Emily A.

2018-02-01

Two-photon microscopy is a powerful tool of current scientific research, allowing optical visualization of structures below the surface of tissues. This is of particular value in neuroscience, where optically accessing regions within the brain is critical for the continued advancement in understanding of neural circuits. However, two-photon imaging at significant depths have typically used Ti:Sapphire based amplifiers that are prohibitively expensive and bulky. In this study, we demonstrate deep tissue two-photon imaging using a compact, inexpensive, turnkey operated Ytterbium fiber laser (Y-Fi, KM Labs). The laser is based on all-normal dispersion (ANDi) that provides short pulse durations and high pulse energies. Depth measurements obtained in ex vivo mouse cortex exceed those obtainable with standard two-photon microscopes using Ti:Sapphire lasers. In addition to demonstrating the capability of deep-tissue imaging in the brain, we investigated imaging depth in highly-scattering white matter with measurements in sciatic nerve showing limited optical penetration of heavily myelinated nerve tissue relative to grey matter.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

GLUT-3 expression in human skeletal muscle

NASA Technical Reports Server (NTRS)

Stuart, C. A.; Wen, G.; Peng, B. H.; Popov, V. L.; Hudnall, S. D.; Campbell, G. A.

2000-01-01

Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

Reflex effects on components of synchronized renal sympathetic nerve activity.

PubMed

DiBona, G F; Jones, S Y

1998-09-01

The effects of peripheral thermal receptor stimulation (tail in hot water, n = 8, anesthetized) and cardiac baroreceptor stimulation (volume loading, n = 8, conscious) on components of synchronized renal sympathetic nerve activity (RSNA) were examined in rats. The peak height and peak frequency of synchronized RSNA were determined. The renal sympathoexcitatory response to peripheral thermal receptor stimulation was associated with an increase in the peak height. The renal sympathoinhibitory response to cardiac baroreceptor stimulation was associated with a decrease in the peak height. Although heart rate was significantly increased with peripheral thermal receptor stimulation and significantly decreased with cardiac baroreceptor stimulation, peak frequency was unchanged. As peak height reflects the number of active fibers, reflex increases and decreases in synchronized RSNA are mediated by parallel increases and decreases in the number of active renal nerve fibers rather than changes in the centrally based rhythm or peak frequency. The increase in the number of active renal nerve fibers produced by peripheral thermal receptor stimulation reflects the engagement of a unique group of silent renal sympathetic nerve fibers with a characteristic response pattern to stimulation of arterial baroreceptors, peripheral and central chemoreceptors, and peripheral thermal receptors.

On the nature of the afferent fibers of oculomotor nerve.

PubMed

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.

Degeneration of oxidative muscle fibers in HTLV-1 tax transgenic mice.

PubMed

Nerenberg, M I; Wiley, C A

1989-12-01

The HTLV-1 tax gene under control of the HTLV-1 long terminal repeat (LTR) was introduced into transgenic mice. Previously tax protein expression in the muscle and peripheral nerves of three independent mouse lines was reported. Here the localization of this transgenic protein at a cellular and subcellular level is described. Tax protein was expressed in oxidative muscle fibers that developed severe progressive atrophy. It localized to the cytoplasma where it was associated with structures resembling degenerating Z bands. This pattern of muscle fiber involvement is similar to that observed in human retroviral associated myopathy. This transgenic mouse model suggests that preferential expression of the HTLV-1 viral promoter in oxidative muscle fibers may explain the productive infection of these fibers in HTLV-1 myopathy.

Design of barrier coatings on kink-resistant peripheral nerve conduits

PubMed Central

Clements, Basak Acan; Bushman, Jared; Murthy, N Sanjeeva; Ezra, Mindy; Pastore, Christopher M; Kohn, Joachim

2016-01-01

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. PMID:26977288

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

PubMed

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.

Intraobserver reproducibility of retinal nerve fiber layer measurements using scanning laser polarimetry and optical coherence tomography in normal and ocular hypertensive subjects.

PubMed

Lleó-Pérez, A; Ortuño-Soto, A; Rahhal, M S; Martínez-Soriano, F; Sanchis-Gimeno, J A

2004-01-01

To evaluate quantitatively the intraobserver reproducibility of measurements of the retinal nerve fiber layer (RNFL) in healthy subjects and an ocular hypertensive population using two nerve fiber analyzers. Sixty eyes of normal (n=30) and ocular hypertensive subjects (n=30) were consecutively recruited for this study and underwent a complete ophthalmologic examination and achromatic automated perimetry. RNFL were measured using scanning laser polarimeter (GDx-VCC) and optical coherence tomography (OCT Model 3000). Reproducibility of the RNFL measurements obtained with both nerve fiber analyzers were compared using the coefficient of variation. In both groups the authors found fair correlations between the two methods in all ratio and thickness parameters. The mean coefficient of variation for measurement of the variables ranged from 2.24% to 13.12% for GDx-VCC, and from 5.01% to 9.24% for OCT Model 3000. The authors could not detect any significant differences between healthy and ocular hypertensive eyes, although in normal eyes the correlations improved slightly. Nevertheless, the test-retest correlation was slightly better for GDx-VCC than for OCT Model 3000 (5.55% and 7.11%, respectively). Retinal mapping software of both nerve fiber analyzers allows reproducible measurement of RNFL in both healthy subjects and ocular hypertensive eyes, and shows fair correlations and good intraobserver reproducibility. However, in our study, GDx showed a better test-retest correlation.

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis.

PubMed

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70-120 m/s), and the second component originated from fibers (Type A γ ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

Microneurography in rats: a minimally invasive method to record single C-fiber action potentials from peripheral nerves in vivo.

PubMed

Serra, Jordi; Bostock, Hugh; Navarro, Xavier

2010-02-19

Microneurography is a method suitable for recording intraneural single or multiunit action potentials in conscious subjects. Microneurography has rarely been applied to animal experiments, where more invasive methods, like the teased fiber recording technique, are widely used. We have tested the feasibility of microneurographic recordings from the peripheral nerves of rats. Tungsten microelectrodes were inserted into the sciatic nerve at mid-thigh level. Single or multiunit action potentials evoked by regular electrical stimulation were recorded, digitized and displayed as a raster plot of latencies. The method allows unambiguous recording and recognition of single C-fiber action potentials from an in vivo preparation, with minimal disruption of the nerve being recorded. Multiple C-fibers can be recorded simultaneously for several hours, and if the animal is allowed to recover, repeated recording sessions can be obtained from the same nerve at the same level over a period of weeks or months. Also, single C units can be functionally identified by their changes in latency to natural stimuli, and insensitive units can be recognized as 'silent' nociceptors or sympathetic efferents by their distinctive profiles of activity-dependent slowing during repetitive electrical stimulation, or by the effect on spontaneous efferent activity of a proximal anesthetic block. Moreover, information about the biophysical properties of C axons can be obtained from their latency recovery cycles. Finally, we show that this preparation is potentially suitable for the study of C-fiber behavior in models of neuropathies and nerve lesions, both under resting conditions and in response to drug administration.

Influence of myelinated retinal nerve fibers on retinal vessel density measurement with AngioVue OCT angiography.

PubMed

Holló, Gábor

2016-12-01

Myelinated retinal nerve fibers (MRNF) represent an asymptomatic developmental anomaly in which myelin sheaths extend to a group of retinal nerve fibers along their intraocular portion. The additional volume of the myelin sheaths causes displacement of the axons toward the vitreous body. We investigated the effect of localized MRNF on peripapillary vessel density measurement results using optical coherence tomography (OCT) angiography. Peripapillary angioflow density measurements (PAFD, % of the analyzed retinal area) were made with the AngioVue OCT (Optovue Inc., Fremont, USA). In both cases, the predominant position of MRNF was inferonasal to the disk. Vessel density was clearly greater in the area of the MRNF than in the surrounding retina in the optic nerve head (ONH) level, but it was lower than in the surrounding retina in the retinal nerve fiber layer (RNFL) level. In the ONH level, PAFD was higher in the MRNF area than in the spatially corresponding superonasal area (Case 1: 64.6 vs. 57.6 %; Case 2: 65.8 vs. 56.3 %). In contrast, in the RNFL level, PAFD was lower in the MRNF area than in the corresponding superonasal area (Case 1: 60.1 vs. 65.4 %; Case 2: 46.5 vs. 58.5 %). Our cases show that the effect of MRNF on OCT angiography vessel density is different in the different measurement layers. Clinicians may separate decreased vessel density caused by anterior RNFL displacement in MRNF areas from that caused by nerve fiber damage in optic neuropathies by evaluating PAFD in both the ONH and RNFL levels.

Multiple sclerosis and optic nerve: an analysis of retinal nerve fiber layer thickness and color Doppler imaging parameters

PubMed Central

Akçam, H T; Capraz, I Y; Aktas, Z; Batur Caglayan, H Z; Ozhan Oktar, S; Hasanreisoglu, M; Irkec, C

2014-01-01

Purpose To compare both retinal nerve fiber layer thickness and orbital color Doppler ultrasonography parameters in patients with multiple sclerosis (MS) versus healthy controls. Methods This is an observational case–control study. Forty eyes from MS patients and twenty eyes from healthy volunteers were examined. Eyes were classified into three groups as group 1, eyes from MS patients with previous optic neuritis (n=20); group 2, eyes from MS patients without previous optic neuritis (n=20); and group 3, eyes from healthy controls (n=20). Following complete ophthalmologic examination and retinal nerve fiber layer thickness measurement for each group, blood flow velocities of posterior ciliary arteries, central retinal artery, ophthalmic artery, and superior ophthalmic vein were measured. Pourcelot index (resistive index), an indicator of peripheral vascular resistance, was also calculated. The statistical assessment was performed with the assistance of Pearson's Chi-square test, Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's correlation test. Results The studied eyes exposed similar values in terms of intraocular pressure and central corneal thickness, implying no evidence in favor of glaucoma. All nerve fiber layer thickness values, except superior nasal quadrants, in group 1 were found to be significantly thinner than groups 2 and 3. Blood flow velocity and mean resistivity index parameters were similar in all the groups. Conclusions In MS patients, especially with previous optic neuritis, diminished retinal nerve fiber layer thickness was observed. Contrary to several studies in the current literature, no evidence supporting potential vascular origin of ocular involvement in MS was found. PMID:25081285

Phenotyping sensory nerve endings in vitro in the mouse

PubMed Central

Zimmermann, Katharina; Hein, Alexander; Hager, Ulrich; Kaczmarek, Jan Stefan; Turnquist, Brian P; Clapham, David E; Reeh, Peter W

2014-01-01

This protocol details methods to identify and record from cutaneous primary afferent axons in an isolated mammalian skin–saphenous nerve preparation. The method is based on extracellular recordings of propagated action potentials from single-fiber receptive fields. Cutaneous nerve endings show graded sensitivities to various stimulus modalities that are quantified by adequate and controlled stimulation of the superfused skin with heat, cold, touch, constant punctate pressure or chemicals. Responses recorded from single-fibers are comparable with those obtained in previous in vivo experiments on the same species. We describe the components and the setting-up of the basic equipment of a skin–nerve recording station (few days), the preparation of the skin and the adherent saphenous nerve in the mouse (15–45 min) and the isolation and recording of neurons (approximately 1–3 h per recording). In addition, stimulation techniques, protocols to achieve single-fiber recordings, issues of data acquisition and action potential discrimination are discussed in detail. PMID:19180088

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

PubMed Central

Baumann, Otto; Dames, Petra; Kühnel, Dana; Walz, Bernd

2002-01-01

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. PMID:12095424

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

PubMed

Baumann, Otto; Dames, Petra; Kühnel, Dana; Walz, Bernd

2002-06-24

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 controlled 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. 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. 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.

Structural complexes in the squid giant axon membrane sensitive to ionic concentrations and cardiac glycosides

PubMed Central

Villegas, GM; Villegas, J

1976-01-01

Giant nerve fibers of squid Sepioteuthis sepiodea were incubated for 10 min in artificial sea water (ASW) under control conditions, in the absence of various ions, and in the presence of cardiac glycosides. The nerve fibers were fixed in OsO(4) and embedded in Epon, and structural complexes along the axolemma were studied. These complexes consist of a portion of axolemma exhibiting a three-layered substructure, an undercoating of a dense material (approximately 0.1μm in length and approximately 70-170 A in thickness), and a narrowing to disappearance of the axon-Schwann cell interspace. In the controls, the incidence of complexes per 1,000μm of axon perimeter was about 137. This number decreased to 10-25 percent when magnesium was not present in the incubating media, whatever the calcium concentration (88, 44, or 0 mM). In the presence of magnesium, the number and structural features of the complexes were preserved, though the number decreased to 65 percent when high calcium was simultaneously present. The complexes were also modified and decreased to 26-32 percent by incubating the nerves in solutions having low concentrations of sodium and potassium. The adding of 10(-5) M ouabain or strophanthoside to normal ASW incubating solution decreased them to 20-40 percent. Due to their sensitivity to changes in external ionic concentrations and to the presence of cardiac glycosides, the complexes are proposed to represent the structural correlate of specialized sites for active ion transport, although other factors may be involved. PMID:1254642

Effectiveness of fibrin adhesive in facial nerve anastomosis in dogs compared with standard microsuturing technique.

PubMed

Attar, Bijan Movahedian; Zalzali, Haidar; Razavi, Mohammad; Ghoreishian, Mehdi; Rezaei, Majid

2012-10-01

Epineural suturing is the most common technique used for peripheral nerve anastomosis. In addition to the foreign body reaction to the suture material, the surgical duration and difficulty of suturing in confined anatomic locations are major problems. We evaluated the effectiveness of fibrin glue as an acceptable alternative for nerve anastomosis in dogs. Eight adult female dogs weighing 18 to 24 kg were used in the present study. The facial nerve was transected bilaterally. On the right side, the facial nerve was subjected to epineural suturing; and on the left side, the nerve was anastomosed using fibrin adhesive. After 16 weeks, the nerve conduction velocity and proportion of the nerve fibers that crossed the anastomosis site were evaluated and compared for the epineural suture (right side) and fibrin glue (left side). The data were analyzed using the paired t test and univariate analysis of variance. The mean postoperative nerve conduction velocity was 29.87 ± 7.65 m/s and 26.75 ± 3.97 m/s on the right and left side, respectively. No statistically significant difference was found in the postoperative nerve conduction velocity between the 2 techniques (P = .444). The proportion of nerve fibers that crossed the anastomotic site was 71.25% ± 7.59% and 72.25% ± 8.31% on the right and left side, respectively. The histologic evaluation showed no statistically significant difference in the proportion of the nerve fibers that crossed the anastomotic site between the 2 techniques (P = .598). The results suggest that the efficacies of epineural suturing and fibrin gluing in peripheral nerve anastomosis are similar. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Palisade endings: cholinergic sensory organs or effector organs?

PubMed

Blumer, Roland; Konakci, Kadriye Zeynep; Pomikal, Christine; Wieczorek, Grazyna; Lukas, Julius-Robert; Streicher, Johannes

2009-03-01

This study aims to complement the authors' prior findings on palisade endings in extraocular muscles (EOMs) of monkeys, and to clarify whether palisade endings are cholinergic motor or cholinergic sensory. Macaque monkeys (Macaca fascicularis, n = 10) of both sexes were analyzed using three-dimensional (3D) reconstructions, confocal laser scanning microscopy (CLSM), and conventional/immuno transmission electron microscopy (TEM). For CLSM, we used three combinations of triple fluorescent labeling. EOM wholemounts were labeled with cholinergic markers, including choline acetyltransferase (ChAT), choline transporter (ChT), vesicular acetylcholine transporter (VAChT), and a classical postsynaptic marker for motor terminals, namely alpha-bungarotoxin. Muscle fibers were counterstained with phalloidin. 3D reconstructions were done of triple-labeled palisade endings. For immuno TEM, tissue was labeled with antibody against ChAT. Concordant with prior findings, the authors demonstrated that palisade endings at the muscle fiber tips arose from nerve fibers that are ChAT-positive. In 25% of the cases, axons forming palisade endings established multiple neuromuscular contacts outside the palisade complex. Such additional neuromuscular contacts were motor terminals, as demonstrated by alpha-bungarotoxin binding. All palisade endings established nerve terminals on the tendon. In 40% of the palisade endings, nerve terminals were observed on the muscle fiber as well. Neurotendinous contacts and neuromuscular contacts in palisade endings were ChT/ChAT/VAChT-immunoreactive. Neuromuscular contacts exhibited structural features of motor terminals and were also alpha-bungarotoxin positive. The present study ascertained that palisade endings are cholinergic motor organs. Therefore, it was concluded that palisade endings are not candidates to provide eye-position signals.

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

NASA Astrophysics Data System (ADS)

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 hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.

Cholera toxin B subunit labeling in lamina II of spinal cord dorsal horn following chronic inflammation in rats.

PubMed

Ma, Qing Ping; Tian, Li

2002-07-26

We have investigated the effect of inflammation on the labeling pattern of cholera toxin B subunit (CTB)-conjugated horseradish peroxidase, an A-fiber marker, by an intra-sciatic nerve injection of the tracer. Following chronic inflammation in one hind paw in rats, there was substantial CTB labeling in lamina II of the spinal dorsal horn, which is normally absent. However, there was no change in the labeling pattern of wheat germ agglutinin or fluoride resistant acid phosphatase/thiamine monophosphatase, two C-fiber markers. The CTB labeling in lamina II after peripheral nerve injury has been interpreted as central sprouting of A-fibers or uptake of the tracer by injured C-fibers. Our results suggest that chronic inflammation and nerve injury may share some common mechanisms in generating allodynia and hyperalgesia.

Sciatic endometriosis induces mechanical hypersensitivity, segmental nerve damage, and robust local inflammation in rats

PubMed Central

Chen, S.; Xie, W.; Strong, J. A.; Jiang, J.; Zhang, J.-M.

2015-01-01

Background Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals. Methods We developed a rat model for sciatic endometriosis by grafting a piece of autologous uterine tissue around the sciatic nerve. Control animals underwent a similar surgery but received a graft of pelvic fat tissue. Results The uterine grafts survived and developed fluid filled cysts; the adjacent nerve showed signs of swelling and damage. Mechanical and cold hypersensitivity and allodynia of the ipsilateral hindpaw developed gradually over the first two weeks after the surgery, peaked at 2 to 5 weeks, and was almost resolved by 7 weeks. Control animals showed only minor changes in these pain behaviors. Histological signs of inflammation in the uterine graft and in the adjacent nerve were observed at 3 weeks but were resolving by 7 weeks. In vivo fiber recording showed increased spontaneous activity, especially of C fibers, in sciatic nerve proximal to the uterine graft. Several pro-inflammatory cytokines including interluekin-18, VEGF, fractalkine, and MIP-1α, were elevated in the uterine graft plus sciatic nerve samples, compared to samples from normal nerve or nerve plus fat graft. Growth associated protein 43 (GAP43), a marker of regenerating nerve fibers, was observed in the adjacent sciatic nerve as well as in the uterine graft. Conclusions This model shared many features with other rat models of endometriosis, but also had some unique features more closely related to neuropathic pain models. PMID:26688332

A New Preparation Method for Anisotropic Silk Fibroin Nerve Guidance Conduits and Its Evaluation In Vitro and in a Rat Sciatic Nerve Defect Model

PubMed Central

Schuh, Christina; Halbweis, Robert; Pajer, Krisztián; Márton, Gábor; Hopf, Rudolf; Mosia, Shorena; Rünzler, Dominik; Redl, Heinz; Nógrádi, Antal; Hausner, Thomas

2015-01-01

Over the past decade, silk fibroin (SF) has been emergently used in peripheral nerve tissue engineering. Current approaches aiming at producing SF-based nerve guidance conduits (SF-NGCs) used dissolved silk based on either aqueous solutions or organic solvents. In this study, we describe a novel procedure to produce SF-NGCs: A braided tubular structure of raw Bombyx mori silk is subsequently processed with the ternary solvent CaCl2/H2O/ethanol, formic acid, and methanol to improve its mechanical and topographical characteristics. Topographically, the combination of the treatments results in a fusion of the outer single silk fibers to a closed layer with a thickness ranging from about 40 to 75 μm. In contrast to the outer wall, the inner lumen (not treated with processing solvents) still represents the braided structure of single fibers. Mechanical stability, elasticity, and kink characteristics were evaluated with a custom-made test system. The modification procedure described here drastically improved the elastic properties of our tubular raw scaffold, favoring its use as a NGC. A cell migration assay with NIH/3T3-fibroblasts revealed the impermeability of the SF-NGC wall for possible invading and scar-forming cells. Moreover, the potential of the SF-NGC to serve as a substratum for Schwann cells has been demonstrated by cytotoxicity tests and live-dead stainings of Schwann cells grown on the inner surface of the SF-NGC. In vivo, the SF-NGC was tested in a rat sciatic nerve injury model. In short-term in vivo studies, it was proved that SF-NGCs are not triggering host inflammatory reactions. After 12 weeks, we could demonstrate morphological and functional reinnervation of the distal targets. Filled with collagen, a higher number of axons could be found in the distal to the graft (1678±303), compared with the empty SF-NGC (1274±146). The novel SF-NGC presented here shows promising results for the treatment of peripheral nerve injuries. The modification of braided structures to adapt their mechanical and topographical characteristics may support the translation of SF-based scaffolds into the clinical setting. However, further improvements and the use of extracellular matrix molecules and Schwann cells are suggested to enable silk tube based conduits to bridge long-distance nerve gaps. PMID:25819471

Cornea and ocular lens visualized with three-dimensional confocal microscopy

NASA Astrophysics Data System (ADS)

Masters, Barry R.

1992-08-01

This paper demonstrates the advantages of three-dimensional reconstruction of the cornea and the ocular crystalline lens by confocal microscopy and volume rendering computer techniques. The advantages of noninvasive observation of ocular structures in living, unstained, unfixed tissue include the following: the tissue is in a natural living state without the artifacts of fixation, mechanical sectioning, and staining; the three-dimensional structure can be observed from any view point and quantitatively analyzed; the dynamics of morphological changes can be studied; and the use of confocal microscopic observation results in a reduction of the number of animals required for ocular morphometric studies. The main advantage is that the dynamic morphology of ocular structures can be investigated in living ocular tissue. A laser scanning confocal microscope was used in the reflected light mode to obtain the two- dimensional images from the cornea and the ocular lens of a freshly enucleated rabbit eye. The light source was an argon ion laser with 488 nm wavelength. The microscope objective was a Leitz 25X, NA 0.6 water immersion lens. The 400 micron thick cornea was optically sectioned into 133, three micron sections. The semi-transparent cornea and the in-situ ocular lens was visualized as high resolution, high contrast two-dimensional images. The under sampling resulted in a three-dimensional visualization rendering in which the corneal thickness (z-axis) is compressed. The structures observed in the cornea include: superficial epithelial cells and their nuclei, basal epithelial cells and their `beaded' cell borders, basal lamina, nerve plexus, nerve fibers, free nerve endings in the basal epithelial cells, nuclei of stromal keratocytes, and endothelial cells. The structures observed in the in-situ ocular lens include: lens capsule, lens epithelial cells, and individual lens fibers.

Searching for proprioceptors in human facial muscles.

PubMed

Cobo, Juan L; Abbate, Francesco; de Vicente, Juan C; Cobo, Juan; Vega, José A

2017-02-15

The human craniofacial muscles innervated by the facial nerve typically lack muscle spindles. However these muscles have proprioception that participates in the coordination of facial movements. A functional substitution of facial proprioceptors by cutaneous mechanoreceptors has been proposed but at present this alternative has not been demonstrated. Here we have investigated whether other kinds of sensory structures are present in two human facial muscles (zygomatic major and buccal). Human checks were removed from Spanish cadavers, and processed for immunohistochemical detection of nerve fibers (neurofilament proteins and S100 protein) and two putative mechanoproteins (acid-sensing ion channel 2 and transient receptor potential vanilloid 4) associated with mechanosensing. Nerves of different calibers were found in the connective septa and within the muscle itself. In all the muscles analysed, capsular corpuscle-like structures resembling elongated or round Ruffini-like corpuscles were observed. Moreover the axon profiles within these structures displayed immunoreactivity for both putative mechanoproteins. The present results demonstrate the presence of sensory structures in facial muscles that can substitute for typical muscle spindles as the source of facial proprioception. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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 crumbled at the 7th PSD and no regeneration was seen at the 21st PSD. Changes in NT-3: Positive staining of NT-3 was largely observed in axons at the 7th PSD, although little NT-3 was seen in the normal fibers. Facial palsy of the rats in group 2 was more extensive than that in group 1 and their function partly recovers at the 21st PSD. The fibres' degeneration occurs not only dispersed throughout the injury site but also occurred throught the length of the nerve. NT-3 immunoreactivity increased in activated fibers after partial transection.

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

PubMed

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.

The nervus terminalis of the guinea pig: a new luteinizing hormone-releasing hormone (LHRH) neuronal system.

PubMed

Schwanzel-Fukuda, M; Silverman, A J

1980-05-15

Immunoreactive LHRH-like material has been found in the cells and fibers of the nervus terminalis in fetal and adult guinea pig brains. LHRH-containing neurons and axons are seen in the nasal mucosa intermingled with fibers of the olfactory nerves, in ganglia along the ventromedial surfaces of the olfactory bulbs and forebrain, and in clusters surrounding perforating branches of the anterior cerebral artery in the regions of the septal nuclei and olfactory tubercle. Nonreactive neurons are found adjacent to the LHRH-positive cells in all of the ganglia. LHRH-immunoreactive cells and axons of the nervus terminalis are in intimate contact with cerebral blood vessels and the cerebrospinal fluid along the intracranial course of this nerve, deep to the meninges. The possible involvement of these structures in the neural mechanisms of sexual behavior and the neurohormonal regulation of reproductive function are discussed.

[Conversion of sound into auditory nerve action potentials].

PubMed

Encke, J; Kreh, J; Völk, F; Hemmert, W

2016-11-01

Outer hair cells play a major role in the hearing process: they amplify the motion of the basilar membrane up to a 1000-fold and at the same time sharpen the excitation patterns. These patterns are converted by inner hair cells into action potentials of the auditory nerve. Outer hair cells are delicate structures and easily damaged, e. g., by overexposure to noise. Hearing aids can amplify the amplitude of the excitation patterns, but they cannot restore their degraded frequency selectivity. Noise overexposure also leads to delayed degeneration of auditory nerve fibers, particularly those with low a spontaneous rate, which are important for the coding of sound in noise. However, this loss cannot be diagnosed by pure-tone audiometry.

Dietary correlates associated with the mental foramen in primates: implications for interpreting the fossil record.

PubMed

Muchlinski, Magdalena N; Deane, Andrew S

2016-07-01

The mandibular nerve is a sensory and motor nerve that innervates the muscles of mastication, the lower dentition, and the lower lip and surrounding structures. Although this nerve contains both efferent and afferent fibers, the mental nerve, a terminal branch of the mandibular nerve, is a strictly sensory nerve that exits the mental foramen and innervates the lower lip, the skin overlaying the mandible, and the oral mucosa around the mandible. Osteological foramina are often used as proxies for nerve cross section area and they often correlate well with some aspect of a primate's ecology (e.g., optic foramen and visual acuity). The primary objective of this study is to explore the correlation between the mental foramen and dietary preference among primates. The mental foramen of 40 primate species (n = 180) was measured from 3-D surface models of the mandible. Both conventional and phylogenetic tests indicate that although frugivores have larger mental foramina than folivores, the differences were not significant. These results show that while structures like the infraorbital foramen correlate well with diet and touch sensitivity, the mental foramen does not. Based on these findings, the mental foramen is not a suggested morphological character for interpreting of the fossil record. J. Morphol. 277:978-985, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PubMed

Duncker, Tobias; Lee, Winston; Jiang, Fan; Ramachandran, Rithambara; Hood, Donald C; Tsang, Stephen H; Sparrow, Janet R; Greenstein, Vivienne C

2018-01-01

To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

The nervus terminalis in the chick: a FMRFamide-immunoreactive and AChE-positive nerve.

PubMed

Wirsig-Wiechmann, C R

1990-07-16

The chick terminal nerve (TN) was examined by immunocytochemical and histochemical methods. Molluscan cardioexcitatory peptide-immunoreactive (FMRFamide-ir) and acetylcholinesterase (AChE)-positive TN perikarya and fibers were distributed along olfactory and trigeminal nerves. FMRFamide-ir TN fibers terminated in the olfactory lamina propria and epithelium and in ganglia along the rostroventral nasal septum. This initial description of several populations of avian TN neurons should provide the foundation for future developmental studies of this system.

Autonomic nerve development contributes to prostate cancer progression.

PubMed

Magnon, Claire; Hall, Simon J; Lin, Juan; Xue, Xiaonan; Gerber, Leah; Freedland, Stephen J; Frenette, Paul S

2013-07-12

Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.

The gross anatomy of the renal sympathetic nerves revisited.

PubMed

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.

Distribution of TRPV1- and TRPV2-immunoreactive afferent nerve endings in rat trachea.

PubMed

Yamamoto, Yoshio; Sato, Yoshikazu; Taniguchi, Kazuyuki

2007-12-01

Nociception in the trachea is important for respiratory modulation. We investigated the distribution, neurochemical characteristics, and origin of nerve endings with immunoreactivity for candidate sensor channels, TRPV1 and TRPV2, in rat trachea. In the epithelial layer, the intraepithelial nerve endings and dense subepithelial network of nerve fibers were immunoreactive for TRPV1. In contrast, TRPV2 immunoreactivity was observed mainly in nerve fibers of the tracheal submucosal layer and in several intrinsic ganglion cells in the peritracheal plexus. Double immunostaining revealed that some TRPV1-immunoreactive nerve fibers were also immunoreactive for substance P or calcitonin gene-related peptide, but neither neuropeptide colocalized with TRPV2. Injection of the retrograde tracer, fast blue, into the tracheal wall near the thoracic inlet demonstrated labeled neurons in the jugular, nodose, and dorsal root ganglia at segmental levels of C2-C8. In the jugular and nodose ganglia, 59.3% (70/118) and 10.7% (17/159), respectively, of fast blue-labeled neurons were immunoreactive for TRPV1, compared to 8.8% (8/91) and 2.6% (5/191) for TRPV2-immunoreactive. Our results indicate that TRPV1-immunoreactive nerve endings are important for tracheal nociception, and the different expression patterns of TRPV1 and TRPV2 with neuropeptides may reflect different subpopulations of sensory neurons.

Receptive fields and gustatory responsiveness of frog glossopharyngeal nerve. A single fiber analysis

PubMed Central

1990-01-01

Receptive fields and responsiveness of single fibers of the glossopharyngeal (IXth) nerve were investigated using electrical, gustatory (NaCl, quinine HCl, acetic acid, water, sucrose, and CaCl2), thermal, and mechanical stimulation of the single fungiform papillae distributed on the dorsal tongue surface in frogs. 172 single fibers were isolated. 58% of these fibers (99/172) were responsive to at least one of the gustatory stimuli (taste fibers), and the remaining 42% (73/172) were responsive only to touch (touch fibers). The number of papillae innervated by a single fiber (receptive field) was between 1 and 17 for taste fibers and between 1 and 10 for touch fibers. The mean receptive field of taste fibers (X = 6.6, n = 99) was significantly larger than that of touch fibers (X = 3.6, n = 73) (two-tailed t test, P less than 0.001). In experiments with natural stimulation of single fungiform papillae, it was found that every branch of a single fiber has a similar responsiveness. Taste fibers were classified into 14 types (Type N, Q, A, NA, NCa, NCaA, NCaW, NCaAW, NCaWS, NQ, NQA, NQAS, NQWarm, Multiple) on the basis of their responses to gustatory and thermal stimuli. The time course of the response in taste fibers was found to be characteristic of their types. For example, the fibers belonging to Type NQA showed phasic responses, those in Type NCa showed tonic responses, etc. These results indicate that there are several groups of fibers in the frog IXth nerve and that every branch of an individual fiber has a similar responsiveness to the parent fiber. PMID:2374001

Microcircuits in the Nervous System

ERIC Educational Resources Information Center

Shepherd, Gordon M.

1978-01-01

Nerve circuits are usually analyzed in terms of the axon, the long fiber of the nerve cell. It now appears that there are many circuits involving only the nerve cell's shorter extensions, the dendrites. (Author/BB)

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

PubMed Central

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Background Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Materials and methods Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types Aα and Aβ fibers) with a large conduction velocity (70–120 m/s), and the second component originated from fibers (Type Aγ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. Results We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Conclusion Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders. PMID:29731661

The Relationship between Retinal Ganglion Cell Axon Constituents and Retinal Nerve Fiber Layer Birefringence in the Primate

PubMed Central

Pocock, Ginger M.; Aranibar, Roberto G.; Kemp, Nate J.; Specht, Charles S.; Markey, Mia K.; Rylander, H.G.

2009-01-01

Purpose To determine the degree of correlation between spatial characteristics of the retinal nerve fiber layer (RNFL) birefringence (ΔnRNFL) surrounding the optic nerve head (ONH) with the corresponding anatomy of retinal ganglion cell (RGC) axons and their respective organelles. Methods RNFL phase retardation per unit depth (PR/UD, proportional to ΔnRNFL) was measured in two cynomolgus monkeys using enhanced polarization-sensitive optical coherence tomography (EPS-OCT). The monkeys were perfused with glutaraldehyde and eyes were enucleated and prepared for transmission electron microscopy (TEM) histological analysis. Morphological measurements from TEM images were used to estimate values of neurotubule density (ρRNFL), axoplasmic area (Ax) mode, axon area (Aa) mode, slope (u) of neurotubule number versus axoplasmic area [neurotubule packing density], fractional area of axoplasm in the nerve fiber bundle (f), mitochondrial fractional area in the nerve fiber bundle (xm), mitochondriated axon profile fraction (mp), and length of axonal membrane profiles per unit nerve fiber bundle area (Lam/Ab). Registered PR/UD and morphological parameters from corresponding angular sections were then correlated using Pearson’s correlation and multi-level models. Results In one eye, there was a statistically significant correlation between PR/UD and ρRNFL (r = 0.67, P =0.005) and between PR/UD and neurotubule packing density (r = 0.70, P = 0.002). Correlation coefficients of r = 0.81 (P=0.01) and r = 0.50 (P = 0.05) were observed between PR/UD and (Ax) mode for each respective subject. Conclusion Neurotubules are the primary source of birefringence in the RNFL of the primate retina. PMID:19494208

Influence of limb temperature on cutaneous silent periods.

PubMed

Kofler, Markus; Valls-Solé, Josep; Vasko, Peter; Boček, Václav; Štetkárová, Ivana

2014-09-01

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by small-diameter afferents (A-delta fibers) and large-diameter efferents (alpha motoneurons). The effect of limb temperature on CSPs has so far not been assessed. In 27 healthy volunteers (11 males; age 22-58 years) we recorded median nerve motor and sensory action potentials, median nerve F-wave and CSPs induced by noxious digit II stimulation in thenar muscles in a baseline condition at room temperature, and after randomly submersing the forearm in 42 °C warm or 15 °C cold water for 20 min each. In cold limbs, distal and proximal motor and sensory latencies as well as F-wave latencies were prolonged. Motor and sensory nerve conduction velocities were reduced. Compound motor and sensory nerve action potential amplitudes did not differ significantly from baseline. CSP onset and end latencies were more delayed than distal and proximal median nerve motor and sensory latencies, whereas CSP duration was not affected. In warm limbs, opposite but smaller changes were seen in nerve conduction studies and CSPs. The observed CSP shift "en bloc" towards longer latencies without affecting CSP duration during limb cooling concurs with slower conduction velocity in both afferent and efferent fibers. Disparate conduction slowing in afferents and efferents, however, suggests that nociceptive EMG suppression is mediated by fibers of different size in the afferent than in the efferent arm, indirectly supporting the contribution of A-delta fibers as the main afferent input. Limb temperature should be taken into account when testing CSPs in the clinical setting, as different limb temperatures affect CSP latencies more than large-diameter fiber conduction function. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Motor nerve transplantation.

PubMed

Gray, W P; Keohane, C; Kirwan, W O

1997-10-01

The motor nerve transplantation (MNT) technique is used to transfer an intact nerve into a denervated muscle by harvesting a neurovascular pedicle of muscle containing motor endplates from the motor endplate zone of a donor muscle and implanting it into a denervated muscle. Thirty-six adult New Zealand White rabbits underwent reinnervation of the left long peroneal (LP) muscle (fast twitch) with a motor nerve graft from the soleus muscle (slow twitch). The right LP muscle served as a control. Reinnervation was assessed using microstimulatory single-fiber electromyography (SFEMG), alterations in muscle fiber typing and grouping, and isometric response curves. Neurofilament antibody was used for axon staining. The neurofilament studies provided direct evidence of nerve growth from the motor nerve graft into the adjacent denervated muscle. Median motor endplate jitter was 13 microsec preoperatively, and 26 microsec at 2 months, 29.5 microsec at 4 months, and 14 microsec at 6 months postoperatively (p < 0.001). Isometric tetanic tension studies showed a progressive functional recovery in the reinnervated muscle over 6 months. There was no histological evidence of aberrant reinnervation from any source outside the nerve pedicle. Isometric twitch responses and adenosine triphosphatase studies confirmed the conversion of the reinnervated LP muscle to a slow-type muscle. Acetylcholinesterase studies confirmed the presence of functioning motor endplates beneath the insertion of the motor nerve graft. It is concluded that the MNT technique achieves motor reinnervation by growth of new nerve fibers across the pedicle graft into the recipient muscle.

Diffusion Tensor Imaging Tractography Detecting Isolated Oculomotor Nerve Damage After Traumatic Brain Injury.

PubMed

Jacquesson, Timothée; Frindel, Carole; Cotton, Francois

2017-04-01

A 24-year-old woman was hit by a bus and suffered an isolated complete oculomotor nerve palsy. Computed tomography scan did not show a skull base fracture. T2*-weighted magnetic resonance imaging revealed petechial cerebral hemorrhages sparing the brainstem. T2 constructive interference in steady state suggested a partial sectioning of the left oculomotor nerve just before entering the superior orbital fissure. Diffusion tensor imaging fiber tractography confirmed a sharp arrest of the left oculomotor nerve. This recent imaging technique could be of interest to assess white fiber damage and help make a diagnosis or prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Surgical anatomy of the prostate in the era of radical robotic prostatectomy.

PubMed

Walz, Jochen; Graefen, Markus; Huland, Hartwig

2011-05-01

New insights in the anatomy of the prostate and the surrounding tissue evolve the technique of radical prostatectomy for the treatment of prostate cancer. Regarding the course of the erectile nerves along the prostate, recent studies confirmed the presence of parasympathetic pro-erectile nerve fibers at the anterolateral aspect of the prostate. Another study of intraoperative electrostimulation of those nerves confirmed an increase in intracavernosal pressure by stimulations between the 1 and 3 o'clock position. Therefore, it is very likely that these anterior nerve fibers have an effect on erectile function. Regarding the urethral sphincter in the male, a study showed no attachment of the external sphincter to the levator ani muscle, probably resulting in an absence of a levator ani support to the continence mechanism. The male urinary sphincter seems to be in isolation responsible for urinary continence. The nerve fibers at the anterolateral aspect of the prostate seem to participate in erectile function, which renders the concept of a high anterior release during nerve sparing beneficial. The isolated urinary sphincter mechanism results in the need to conserve as much urethral length as possible during radical prostatectomy to avoid urinary incontinence.

Neovascularization and neoinnervation of subcutaneously placed nucleus pulposus and the inhibitory effects of certain drugs.

PubMed

Olmarker, Kjell

2005-07-01

An experimental study in the pig with autologous transfer of nucleus pulpous and retroperitoneal fat to the subcutaneous space of the back. To evaluate if there is neovascularization or neoinnervation of subcutaneously placed nucleus pulposus, in comparison to retroperitoneal fat, and under simultaneous treatment by certain antiangiogenetic drugs. It has been suggested that intervertebral discs may be invaded by newly formed blood vessels and nerve fibers following injury of the anulus fibrosus. The nerve fibers have been considered to induce low back pain. However, it is still debated whether such ingrowth may occur and, if present, if this is based on the action of angiogenetic substances in the intervertebral disc or simply by normal would healing. In the first series, autologous nucleus pulposus and retroperitoneal fat was placed subcutaneously in 3 pigs. In the second series, autologous nucleus pulposus was placed subcutaneously with simultaneous treatment with methotrexate (n = 3), celecoxib (n = 3), doxycycline (n = 3), and infliximab (n = 3). After 7 days, the tissue was collected and processed immunohistochemically for the visualization of blood vessels and nerve fibers. There was a number of blood vessels and nerve fibers in the nucleus pulposus samples, while no vessels were observed in the fat samples. Neither methotrexate nor celecoxib seemed to be able to reduce the ingrowth of blood vessels (neovascularization) or nerve fibers (neoinnervation). Treatment by doxycycline and infliximab markedly reduced both neovascularization and neoinnervation. Subcutaneously placed autologous nucleus pulposus displays an ingrowth of newly formed blood vessels and nerve fibers within 7 days, in contrast to retroperitoneal fat. Such ingrowth seems to be reduced by doxycycline and infliximab, 2 cytokine inhibitors. The data suggest that the ingrowth may be induced by bioactive substances within the nucleus pulposus. The clinical importance of these data has yet to be elucidated.

Lack of effectiveness of laser therapy applied to the nerve course and the correspondent medullary roots

PubMed Central

Sousa, Fausto Fernandes de Almeida; Ribeiro, Thaís Lopes; Fazan, Valéria Paula Sassoli; Barbieri, Claudio Henrique

2013-01-01

OBJECTIVE: To investigate the influence of low intensity laser irradiation on the regeneration of the fibular nerve of rats after crush injury. METHODS: Twenty-five rats were used, divided into three groups: 1) intact nerve, no treatment; 2) crushed nerve, no treatment; 3) crush injury, laser irradiation applied on the medullary region corresponding to the roots of the sciatic nerve and subsequently on the course of the damaged nerve. Laser irradiation was carried out for 14 consecutive days. RESULTS: Animals were evaluated by functional gait analysis with the peroneal functional index and by histomorphometric analysis using the total number of myelinated nerve fibers and their density, total number of Schwann cells, total number of blood vessels and the occupied area, minimum diameter of the fiber diameter and G-quotient. CONCLUSION: According to the statistical analysis there was no significant difference among groups and the authors conclude that low intensity laser irradiation has little or no influence on nerve regeneration and functional recovery. Laboratory investigation. PMID:24453650

Incorporation of fiber optic beam shaping into a laparoscopic probe for laser stimulation of the cavernous nerves

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Lagoda, Gwen A.; Mayeh, Mona; Burnett, Arthur L.; Farahi, Faramarz; Fried, Nathaniel M.

2010-02-01

The cavernous nerves (CN) course along the prostate surface and are responsible for erectile function. Improved identification and preservation of the CN's is critical to maintaining sexual potency after prostate cancer surgery. Noncontact optical nerve stimulation (ONS) of the CN's was recently demonstrated in a rat model, in vivo, as a potential alternative to electrical nerve stimulation (ENS) for identification of the CN's during prostate surgery. However, the therapeutic window for ONS is narrow, so optimal design of the fiber optic delivery system is critical for safe, reproducible stimulation. This study describes modeling, assembly, and testing of an ONS probe for delivering a small, collimated, flat-top laser beam for uniform CN stimulation. A direct comparison of the magnitude and response time of the intracavernosal pressure (ICP) for both Gaussian and flat-top spatial beam profiles was performed. Thulium fiber laser radiation (λ=1870 nm) was delivered through a 200-μm fiber, with distal fiber tip chemically etched to convert a Gaussian to flat-top beam profile. The laser beam was collimated to a 1-mm-diameter spot using an aspheric lens. Computer simulations of light propagation were used to optimize the probe design. The 10-Fr (3.4-mm-OD) laparoscopic probe provided a constant radiant exposure at the nerve surface. The probe was tested in four rats, in vivo. ONS of the CN's was performed with a 1-mm-diameter spot, 5- ms pulse duration, and pulse rate of 20 Hz for a duration of 15-30 s. The flat-top laser beam profile consistently produced a faster and higher ICP response at a lower radiant exposure than the Gaussian beam profile due, in part, to easier alignment of the more uniform beam with nerve. With further development, ONS may be used as a diagnostic tool for identification of the CN's during laparoscopic and robotic nerve-sparing prostate cancer surgery.

Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium.

PubMed

Rashwan, Ahmed; Konishi, Hiroyuki; El-Sharaby, Ashraf; Kiyama, Hiroshi

2016-01-01

We investigated the relationship between mouse taste bud development and innervation of the soft palate. We employed scanning electron microscopy and immunohistochemistry using antibodies against protein gene product 9.5 and peripherin to detect sensory nerves, and cytokeratin 8 and α-gustducin to stain palatal taste buds. At E14, nerve fibers were observed along the medial border of the palatal shelves that tracked toward the epithelium. At E15.5, primordial stages of taste buds in the basal lamina of the soft palate first appeared. At E16, the taste buds became large spherical masses of columnar cells scattered in the soft palate basal lamina. At E17, the morphology and also the location of taste buds changed. At E18-19, some taste buds acquired a more elongated shape with a short neck, extending a variable distance from the soft palate basal lamina toward the surface epithelium. At E18, mature taste buds with taste pores and perigemmal nerve fibers were observed on the surface epithelium of the soft palate. The expression of α-gustducin was demonstrated at postnatal day 1 and the number of pored taste buds increased with age and they became pear-shaped at 8 weeks. The percent of pored fungiform-like papillae at birth was 58.3% of the whole palate; this increased to 83.8% at postnatal day 8 and reached a maximum of 95.7% at 12 weeks. The innervation of the soft palate was classified into three types of plexuses in relation to taste buds: basal nerve plexus, intragemmal and perigemmal nerve fibers. This study reveals that the nerve fibers preceded the development of taste buds in the palate of mice, and therefore the nerve fibers have roles in the initial induction of taste buds in the soft palate. Copyright © 2015 Elsevier B.V. All rights reserved.

[Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves].

PubMed

Julé, Y

1975-05-01

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.

High-resolution matrix-assisted laser desorption ionization–imaging mass spectrometry of lipids in rodent optic nerve tissue

PubMed Central

Anderson, David M. G.; Mills, Daniel; Spraggins, Jeffrey; Lambert, Wendi S.; Calkins, David J.

2013-01-01

Purpose To develop a method for generating high spatial resolution (10 µm) matrix-assisted laser desorption ionization (MALDI) images of lipids in rodent optic nerve tissue. Methods Ice-embedded optic nerve tissue from rats and mice were cryosectioned across the coronal and sagittal axes of the nerve fiber. Sections were thaw mounted on gold-coated MALDI plates and were washed with ammonium acetate to remove biologic salts before being coated in 2,5-dihydroxybenzoic acid by sublimation. MALDI images were generated in positive and negative ion modes at 10 µm spatial resolution. Lipid identification was performed with a high mass resolution Fourier transform ion cyclotron resonance mass spectrometer. Results Several lipid species were observed with high signal intensity in MALDI images of optic nerve tissue. Several lipids were localized to specific structures including in the meninges surrounding the optic nerve and in the central neuronal tissue. Specifically, phosphatidylcholine species were observed throughout the nerve tissue in positive ion mode while sulfatide species were observed in high abundance in the meninges surrounding the optic nerve in negative ion mode. Accurate mass measurements and fragmentation using sustained off-resonance irradiation with a high mass resolution Fourier transform ion cyclotron resonance mass spectrometer instrument allowed for identification of lipid species present in the small structure of the optic nerve directly from tissue sections. Conclusions An optimized sample preparation method provides excellent sensitivity for lipid species present within optic nerve tissue. This allowed the laser spot size and fluence to be reduced to obtain a high spatial resolution of 10 µm. This new imaging modality can now be applied to determine spatial and molecular changes in optic nerve tissue with disease. PMID:23559852

Upregulation of the axonal growth and the expression of substance P and its NK1 receptor in human allergic contact dermatitis.

PubMed

El-Nour, H; Lundeberg, L; Al-Tawil, R; Granlund, A; Lonne-Rahm, S-B; Nordlind, K

2006-01-01

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.

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

PubMed Central

Ramaswamy, Gomathy; Lombardo, Marco; Devaney, Nicholas

2014-01-01

Glaucoma is the leading cause of preventable blindness in the western world. Investigation of high-resolution retinal nerve fiber layer (RNFL) images in patients may lead to new indicators of its onset. Adaptive optics (AO) can provide diffraction-limited images of the retina, providing new opportunities for earlier detection of neuroretinal pathologies. However, precise processing is required to correct for three effects in sequences of AO-assisted, flood-illumination images: uneven illumination, residual image motion and image rotation. This processing can be challenging for images of the RNFL due to their low contrast and lack of clearly noticeable features. Here we develop specific processing techniques and show that their application leads to improved image quality on the nerve fiber bundles. This in turn improves the reliability of measures of fiber texture such as the correlation of Gray-Level Co-occurrence Matrix (GLCM). PMID:24940551

Rod-Shaped Neural Units for Aligned 3D Neural Network Connection.

PubMed

Kato-Negishi, Midori; Onoe, Hiroaki; Ito, Akane; Takeuchi, Shoji

2017-08-01

This paper proposes neural tissue units with aligned nerve fibers (called rod-shaped neural units) that connect neural networks with aligned neurons. To make the proposed units, 3D fiber-shaped neural tissues covered with a calcium alginate hydrogel layer are prepared with a microfluidic system and are cut in an accurate and reproducible manner. These units have aligned nerve fibers inside the hydrogel layer and connectable points on both ends. By connecting the units with a poly(dimethylsiloxane) guide, 3D neural tissues can be constructed and maintained for more than two weeks of culture. In addition, neural networks can be formed between the different neural units via synaptic connections. Experimental results indicate that the proposed rod-shaped neural units are effective tools for the construction of spatially complex connections with aligned nerve fibers in vitro. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

Ramaswamy, Gomathy; Lombardo, Marco; Devaney, Nicholas

2014-06-01

Glaucoma is the leading cause of preventable blindness in the western world. Investigation of high-resolution retinal nerve fiber layer (RNFL) images in patients may lead to new indicators of its onset. Adaptive optics (AO) can provide diffraction-limited images of the retina, providing new opportunities for earlier detection of neuroretinal pathologies. However, precise processing is required to correct for three effects in sequences of AO-assisted, flood-illumination images: uneven illumination, residual image motion and image rotation. This processing can be challenging for images of the RNFL due to their low contrast and lack of clearly noticeable features. Here we develop specific processing techniques and show that their application leads to improved image quality on the nerve fiber bundles. This in turn improves the reliability of measures of fiber texture such as the correlation of Gray-Level Co-occurrence Matrix (GLCM).

Nervus terminalis, olfactory nerve, and optic nerve representation of luteinizing hormone-releasing hormone in primates.

PubMed

Witkin, J W

1987-01-01

The luteinizing hormone-releasing hormone (LHRH) system was examined immunocytochemically in olfactory bulbs of adult monkeys, including two New World species (squirrel monkey, Saimiri sciureus and owl monkey, Aotus trivirgatus) and one Old World species (cynomolgus macaque, Macaca fasciculata), and in the brain and nasal region of a fetal rhesus macaque Macaca mulatta. LHRH neurons and fibers were found sparsely distributed in the olfactory bulbs in all adult monkeys. There was more LHRH in the accessory olfactory bulb (which is absent in Old World monkeys). In the fetal macaque there was a rich distribution of LHRH neurons and fibers along the pathway of the nervus terminalis, anterior and ventral to the olfactory bulb, and in the nasal septum, with fibers branching into the olfactory epithelium. In addition, there were LHRH neurons and fibers in the optic nerve.

Immunohistochemical study of dental pulp applied with 4-META/MMA-TBB adhesive resin after pulpotomy.

PubMed

Nakamura, M; Inoue, T; Shimono, M

2000-08-01

The purpose of this study was to investigate nerve regeneration and proliferative activity in amputated pulp tissue after the application of 4-META/MMA-TBB adhesive resin (4-META resin). Calcium hydroxide was used as a control material. At 3 days, fibroblast-like cells were positive for proliferating cell nuclear antigen (PCNA) in both 4-META resin- and calcium hydroxide-treated groups and were located mainly within 0.5 mm from the cut surface. Only a few fragmented neurofilament protein (NFP)-positive nerve fibers were observed in this area. At 7 and 14 days, the number of PCNA-positive cells had gradually decreased and regenerated NFP-positive nerve fibers were observed close to the cut surface of the pulp in both groups. At 21 days in the experimental group, several PCNA-positive cells were still found in the area 0.5 mm from the cut surface, and NFP-positive nerve fibers were detected about 0.15-;0.2 mm from the cut surface. In contrast, a dentin bridge was produced under the necrotic layer at 21 days in the control group. PCNA-positive cells were not found underneath the dentin bridge, but NFP-positive nerve fibers had regenerated close to it. These results suggest that although cell differentiation and nerve regeneration are delayed, wound healing occurred even after the application of 4-META resin to exposed pulp surface the same as calcium hydroxide application. Copyright 2000 John Wiley & Sons, Inc.

Schwann cell glycogen selectively supports myelinated axon function.

PubMed

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

2012-09-01

Interruption of energy supply to peripheral axons is a cause of axon loss. We determined whether glycogen was present in mammalian peripheral nerve, and whether it supported axon conduction during aglycemia. We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. 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 compound action potential (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. 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. . Copyright © 2012 American Neurological Association.

Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

PubMed Central

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

2012-01-01

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

Fiber-based polarization-sensitive OCT of the human retina with correction of system polarization distortions

PubMed Central

Braaf, Boy; Vermeer, Koenraad A.; de Groot, Mattijs; Vienola, Kari V.; de Boer, Johannes F.

2014-01-01

In polarization-sensitive optical coherence tomography (PS-OCT) the use of single-mode fibers causes unpredictable polarization distortions which can result in increased noise levels and erroneous changes in calculated polarization parameters. In the current paper this problem is addressed by a new Jones matrix analysis method that measures and corrects system polarization distortions as a function of wavenumber by spectral analysis of the sample surface polarization state and deeper located birefringent tissue structures. This method was implemented on a passive-component depth-multiplexed swept-source PS-OCT system at 1040 nm which was theoretically modeled using Jones matrix calculus. High-resolution B-scan images are presented of the double-pass phase retardation, diattenuation, and relative optic axis orientation to show the benefits of the new analysis method for in vivo imaging of the human retina. The correction of system polarization distortions yielded reduced phase retardation noise, and better estimates of the diattenuation and the relative optic axis orientation in weakly birefringent tissues. The clinical potential of the system is shown by en face visualization of the phase retardation and optic axis orientation of the retinal nerve fiber layer in a healthy volunteer and a glaucoma patient with nerve fiber loss. PMID:25136498

Comparison of peripapillary retinal nerve fiber layer loss and visual outcome in fellow eyes following sequential bilateral non-arteritic anterior ischemic optic neuropathy.

PubMed

Dotan, Gad; Kesler, Anat; Naftaliev, Elvira; Skarf, Barry

2015-05-01

To report on the correlation of structural damage to the axons of the optic nerve and visual outcome following bilateral non-arteritic anterior ischemic optic neuropathy. A retrospective review of the medical records of 25 patients with bilateral sequential non-arteritic anterior ischemic optic neuropathy was performed. Outcome measures were peripapillary retinal nerve fiber layer thickness measured with the Stratus optical coherence tomography scanner, visual acuity and visual field loss. Median peripapillary retinal nerve fiber layer (RNFL) thickness, mean deviation (MD) of visual field, and visual acuity of initially involved NAION eyes (54.00 µm, -17.77 decibels (dB), 0.4, respectively) were comparable to the same parameters measured following development of second NAION event in the other eye (53.70 µm, p = 0.740; -16.83 dB, p = 0.692; 0.4, p = 0.942, respectively). In patients with bilateral NAION, there was a significant correlation of peripapillary RNFL thickness (r = 0.583, p = 0.002) and MD of the visual field (r = 0.457, p = 0.042) for the pairs of affected eyes, whereas a poor correlation was found in visual acuity of these eyes (r = 0.279, p = 0.176). Peripapillary RNFL thickness following NAION was positively correlated with MD of visual field (r = 0.312, p = 0.043) and negatively correlated with logMAR visual acuity (r = -0.365, p = 0.009). In patients who experience bilateral NAION, the magnitude of RNFL loss is similar in each eye. There is a greater similarity in visual field loss than in visual acuity between the two affected eyes with NAION of the same individual.

Truths, errors, and lies around "reflex sympathetic dystrophy" and "complex regional pain syndrome".

PubMed

Ochoa, J L

1999-10-01

The shifting paradigm of reflex sympathetic dystrophy-sympathetically maintained pains-complex regional pain syndrome is characterized by vestigial truths and understandable errors, but also unjustifiable lies. It is true that patients with organically based neuropathic pain harbor unquestionable and physiologically demonstrable evidence of nerve fiber dysfunction leading to a predictable clinical profile with stereotyped temporal evolution. In turn, patients with psychogenic pseudoneuropathy, sustained by conversion-somatization-malingering, not only lack physiological evidence of structural nerve fiber disease but display a characteristically atypical, half-subjective, psychophysical sensory-motor profile. The objective vasomotor signs may have any variety of neurogenic, vasogenic, and psychogenic origins. Neurological differential diagnosis of "neuropathic pain" versus pseudoneuropathy is straight forward provided that stringent requirements of neurological semeiology are not bypassed. Embarrassing conceptual errors explain the assumption that there exists a clinically relevant "sympathetically maintained pain" status. Errors include historical misinterpretation of vasomotor signs in symptomatic body parts, and misconstruing symptomatic relief after "diagnostic" sympathetic blocks, due to lack of consideration of the placebo effect which explains the outcome. It is a lie that sympatholysis may specifically cure patients with unqualified "reflex sympathetic dystrophy." This was already stated by the father of sympathectomy, René Leriche, more than half a century ago. As extrapolated from observations in animals with gross experimental nerve injury, adducing hypothetical, untestable, secondary central neuron sensitization to explain psychophysical sensory-motor complaints displayed by patients with blatantly absent nerve fiber injury, is not an error, but a lie. While conceptual errors are not only forgivable, but natural to inexact medical science, lies particularly when entrepreneurially inspired are condemnable and call for peer intervention.

Distinct localization of peripheral and central types of choline acetyltransferase in the rat cochlea.

PubMed

Kitanishi, Tsuyoshi; Aimi, Yoshinari; Kitano, Hiroya; Suzuki, Mikio; Kimura, Hiroshi; Saito, Atsushi; Shimizu, Takeshi; Tooyama, Ikuo

2013-10-30

We previously discovered a splice variant of choline acetyltransferase (ChAT) mRNA, and designated the variant protein pChAT because of its preferential expression in peripheral neuronal structures. In this study, we examined the immunohistochemical localization of pChAT in rat cochlea and compared the distribution pattern to those of common ChAT (cChAT) and acetylcholinesterase. Some neuronal cell bodies and fibers in the spiral ganglia showed immunoreactivity for pChAT, predominantly the small spiral ganglion cells, indicating outer hair cell type II neurons. In contrast, cChAT- and acetylcholinesterase-positive structures were localized to fibers and not apparent in ganglion cells. After ablation of the cochlear nuclei, many pChAT-positive cochlear nerve fibers became clearly visible, whereas fibers immunopositive for cChAT and acetylcholine esterase disappeared. These results suggested that pChAT and cChAT are localized in different systems of the rat cochlea; pChAT in the afferent and cChAT in the efferent structures.

Distinct Localization of Peripheral and Central Types of Choline Acetyltransferase in the Rat Cochlea

PubMed Central

Kitanishi, Tsuyoshi; Aimi, Yoshinari; Kitano, Hiroya; Suzuki, Mikio; Kimura, Hiroshi; Saito, Atsushi; Shimizu, Takeshi; Tooyama, Ikuo

2013-01-01

We previously discovered a splice variant of choline acetyltransferase (ChAT) mRNA, and designated the variant protein pChAT because of its preferential expression in peripheral neuronal structures. In this study, we examined the immunohistochemical localization of pChAT in rat cochlea and compared the distribution pattern to those of common ChAT (cChAT) and acetylcholinesterase. Some neuronal cell bodies and fibers in the spiral ganglia showed immunoreactivity for pChAT, predominantly the small spiral ganglion cells, indicating outer hair cell type II neurons. In contrast, cChAT- and acetylcholinesterase-positive structures were localized to fibers and not apparent in ganglion cells. After ablation of the cochlear nuclei, many pChAT-positive cochlear nerve fibers became clearly visible, whereas fibers immunopositive for cChAT and acetylcholine esterase disappeared. These results suggested that pChAT and cChAT are localized in different systems of the rat cochlea; pChAT in the afferent and cChAT in the efferent structures. PMID:24194628

[Lipomatosis of nerve: a clinicopathologic analysis of 15 cases].

PubMed

MAO, Rong-jun; YANG, Ke-fei; WANG, Jian

2011-03-01

To study the clinicopathologic features of lipomatosis of nerve (NLS). The clinical, radiologic and pathologic features were analyzed in 15 cases of NLS. There were a total of 10 males and 5 females. The age of patients ranged from 4 to 42 years (mean age = 22.4 years). Eleven cases were located in the upper limbs and 4 cases in the lower limbs. The median nerve was the most common involved nerve. The patients typically presented before 30 years of age (often at birth or in early childhood) with a soft and slowly enlarging mass in the limb, with or without accompanying motor and sensory deficits. Some cases also had macrodactyly and carpal tunnel syndrome. MRI showed the presence of fatty tissue between nerve fascicles, resembling coaxial cable in axial plane and assuming a spaghetti-like appearance in coronal plane. On gross examination, the affected nerve was markedly increased in length and diameter. It consisted of a diffusely enlarged greyish-yellow lobulated fusiform beaded mass within the epineural sheath. Histologically, the epineurium was infiltrated by fibrofatty tissue which separated, surrounded and compressed the usually normal-appearing nerve fascicles, resulting in perineural septation of nerve fascicles and microfascicle formation. The infiltration sometimes resulted in concentric arrangement of perineural cells and pseudo-onion bulb-like hypertrophic changes. The perineurial cells might proliferate, with thickening of collagen fibers, degeneration and atrophic changes of nerve bundles. Immunohistochemical study showed that the nerve fibers expressed S-100 protein, neurofilament and CD56 (weak). The endothelial cells and dendritic fibers were highlighted by CD34. The intravascular smooth muscle cells were positive for muscle-specific actin. NLS is a rare benign soft tissue tumor of peripheral nerve. The MRI findings are characteristic. A definitive diagnosis can be made with histologic examination of tissue biopsy.

Continuous-wave optical stimulation of the rat prostate nerves using an all-single-mode 1455 nm diode laser and fiber system

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2011-03-01

Optical nerve stimulation (ONS) has recently been reported as a potential alternative to electrical nerve stimulation. Continuous-wave (CW) laser stimulation of the prostate cavernous nerves (CN) in a rat model, in vivo, has also been demonstrated in our previous studies. The objective of this study is to present a new all-single-mode-fiber configuration for ONS with the laser operating in CW mode for potential diagnostic applications. An infrared pigtailed single-mode diode laser (λ = 1455 nm) was used in this study for noncontact ONS. This new all-fiber approach introduces several advantages including: (1) a less expensive and more compact ONS system, (2) elimination of alignment of optical components, and (3) an improved spatial beam profile. Successful optical stimulation of the rat CN using this new design was observed after the CN reached a threshold temperature of ~ 41 °C with response times as short as 3 s. Upon further study, this configuration may be useful for identification and preservation of the cavernous nerves during prostate cancer surgery.

LOXL1 deficiency in the lamina cribrosa as candidate susceptibility factor for a pseudoexfoliation-specific risk of glaucoma.

PubMed

Schlötzer-Schrehardt, Ursula; Hammer, Christian M; Krysta, Anita W; Hofmann-Rummelt, Carmen; Pasutto, Francesca; Sasaki, Takako; Kruse, Friedrich E; Zenkel, Matthias

2012-09-01

To test the hypothesis that a primary disturbance in lysyl oxidase-like 1 (LOXL1) and elastin metabolism in the lamina cribrosa of eyes with pseudoexfoliation syndrome constitutes an independent risk factor for glaucoma development and progression. Observational, consecutive case series. Posterior segment tissues obtained from 37 donors with early and late stages of pseudoexfoliation syndrome without glaucoma, 37 normal age-matched control subjects, 5 eyes with pseudoexfoliation-associated open-angle glaucoma, and 5 eyes with primary open-angle glaucoma (POAG). Protein and mRNA expression of major elastic fiber components (elastin, fibrillin-1, fibulin-4), collagens (types I, III, and IV), and lysyl oxidase crosslinking enzymes (LOX, LOXL1, LOXL2) were assessed in situ by quantitative real-time polymerase chain reaction, (immuno)histochemistry, and light and electron microscopy. Lysyl oxidase-dependent elastin fiber assembly was assessed by primary optic nerve head astrocytes in vitro. Expression levels of elastic proteins, collagens, and lysyl oxidases in the lamina cribrosa. Lysyl oxidase-like 1 proved to be the major lysyl oxidase isoform in the normal lamina cribrosa in association with a complex elastic fiber network. Compared with normal and POAG specimens, lamina cribrosa tissues obtained from early and late stages of pseudoexfoliation syndrome without and with glaucoma consistently revealed a significant coordinated downregulation of LOXL1 and elastic fiber constituents on mRNA and protein level. In contrast, expression levels of collagens and other lysyl oxidase isoforms were not affected. Dysregulated expression of LOXL1 and elastic proteins was associated with pronounced (ultra)structural alterations of the elastic fiber network in the laminar beams of pseudoexfoliation syndrome eyes. Inhibition of LOXL1 interfered with elastic fiber assembly by optic nerve head astrocytes in vitro. The findings provide evidence for a pseudoexfoliation-specific elastinopathy of the lamina cribrosa resulting from a primary disturbance in LOXL1 regulation and elastic fiber homeostasis, possibly rendering pseudoexfoliation syndrome eyes more vulnerable to pressure-induced optic nerve damage and glaucoma development and progression. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Afferent fibers and sensory ganglion cells within the oculomotor nerve in some mammals and man. II. Electrophysiological investigations.

PubMed

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

1978-01-01

The main aim of the present study was to localize with electrophysiological techniques the central projections and terminations of the aberrant trigeminal fibres contained in the oculomotor nerve of the lamb. After severing a trigeminal root, single-shock electrical stimulation of the trigeminal axons present in the central stump of the ipsilateral oculomotor nerve evoked field potentials in the area of, i) the subnucleus gelatinosus of the nucleus caudalis trigemini at the level of C1-C2; ii) the main sensory trigeminal nucleus; iii) the descending trigeminal nucleus and tract; iv) the adjacent reticular formation. Units whose discharge rate was influenced by such a stimulation were also found in the same territories. These regions actually exhibited degenerations after cutting an oculomotor nerve. We conclude, therefore, that the trigeminal fibres which leave the Vth nerve at the level of the cavernous sinus and enter the brain stem through the IIIrd nerve, end in the same structures which receive the terminations of the afferent fibres entering the brain stem through the sensory trigeminal root.

Chronic low-frequency stimulation transforms cat masticatory muscle fibers into jaw-slow fibers.

PubMed

Kang, Lucia H D; Hoh, Joseph F Y

2011-09-01

Cat masticatory muscle during regeneration expresses masticatory-specific myofibrillar proteins upon innervation by a fast muscle nerve but acquires the jaw-slow phenotype when innervated by a slow muscle nerve. Here, we test the hypothesis that chronic low-frequency stimulation simulating impulses from the slow nerve can result in masticatory-to-slow fiber-type transformation. In six cats, the temporalis muscle was continuously stimulated directly at 10 Hz for up to 12 weeks using a stimulator affixed to the skull. Stimulated muscles were analyzed by immunohistochemistry using, among others, monoclonal antibodies against masticatory-specific myosin heavy chain (MyHC), myosin binding protein-C, and tropomyosins. Under the electrodes, stimulation induced muscle regeneration, which generated slow fibers. Deep to the electrodes, at two to three weeks, two distinct populations of masticatory fibers began to express slow MyHC: 1) evenly distributed fibers that completely suppressed masticatory-specific proteins but transiently co-expressed fetal MyHCs, and 2) incompletely transformed fibers that express slow and masticatory but not fetal MyHCs. SDS-PAGE confirmed de novo expression of slow MyHC and β-tropomyosin in the stimulated muscles. We conclude that chronic low-frequency stimulation induces masticatory-to-slow fiber-type conversion. The two populations of transforming masticatory fibers may differ in their mode of activation or lineage of their myogenic cells.

Optic nerve axons and acquired alterations in the appearance of the optic disc.

PubMed Central

Wirtschafter, J D

1983-01-01

The pathophysiologic events in optic nerve axons have recently been recognized as crucial to an understanding of clinically significant acquired alterations in the ophthalmoscopic appearance of the optic disc. Stasis and related abnormalities of axonal transport appear to explain most aspects of optic nerve head swelling, including optic disc drusen and retinal cottonwool spots. Loss of axoplasm and axonal death can be invoked to interpret optic disc pallor, thinning and narrowing of rim tissue, changes in the size and outline of the optic cup, laminar dots, atrophy of the retinal nerve fiber layer, and acquired demyelination and myelination of the retinal nerve fiber layer. It is speculated that the axons may also play a role in the mechanical support of the lamina cribrosa in resisting the pressure gradient across the pars scleralis of the optic nerve head. Axons and their associated glial cells may be involved in those cases where "reversibility" of cupping of the optic disc has been reported. The structure, physiology, and experimental pathologic findings of the optic nerve head have been reviewed. Many aspects concerning the final anatomic appearance of the optic nerve head have been explained. However, many questions remain concerning the intermediate mechanisms by which increased intracranial pressure retards the various components of axonal transport in papilledema and by which increased IOP causes axonal loss in glaucoma. Investigation of the molecular biology of axonal constituents and their responses to abnormalities in their physical and chemical milieu could extend our understanding of the events that result from mechanical compression and local ischemia. Moreover, we have identified a need to further explore the role of axons in the pathophysiology of optic disc cupping. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 11 FIGURE 12 FIGURE 13 PMID:6203209

Tyrosine hydroxylase-immunoreactivity and its relations with gonadotropin-releasing hormone and neuropeptide Y in the preoptic area of the guinea pig.

PubMed

Bogus-Nowakowska, Krystyna; Równiak, Maciej; Hermanowicz-Sobieraj, Beata; Wasilewska, Barbara; Najdzion, Janusz; Robak, Anna

2016-12-01

The present study examines the distribution of tyrosine hydroxylase (TH) immunoreactivity and its morphological relationships with neuropeptide Y (NPY)- and gonadoliberin (GnRH)-immunoreactive (IR) structures in the preoptic area (POA) of the male guinea pig. Tyrosine hydroxylase was expressed in relatively small population of perikarya and they were mostly observed in the periventricular preoptic nucleus and medial preoptic area. The tyrosine hydroxylase-immunoreactive (TH-IR) fibers were dispersed troughout the whole POA. The highest density of these fibers was observed in the median preoptic nucleus, however, in the periventricular preoptic nucleus and medial preoptic area they were only slightly less numerous. In the lateral preoptic area, the density of TH-IR fibers was moderate. Two morphological types of TH-IR fibers were distinguished: smooth and varicose. Double immunofluorescence staining showed that TH and GnRH overlapped in the guinea pig POA but they never coexisted in the same structures. TH-IR fibers often intersected with GnRH-IR structures and many of them touched the GnRH-IR perikarya or dendrites. NPY wchich was abundantly present in the POA only in fibers showed topographical proximity with TH-IR structures. Althoug TH-IR perikarya and fibers were often touched by NPY-IR fibers, colocalization of TH and NPY in the same structures was very rare. There was only a small population of fibers which contained both NPY and TH. In conclusion, the morphological evidence of contacts between TH- and GnRH-IR nerve structures may be the basis of catecholaminergic control of GnRH release in the preoptic area of the male guinea pig. Moreover, TH-IR neurons were conatcted by NPY-IR fibers and TH and NPY colocalized in some fibers, thus NPY may regulate catecholaminergic neurons in the POA. Copyright © 2016 Elsevier B.V. All rights reserved.

Nerve-dependent changes in skeletal muscle myosin heavy chain after experimental denervation and cross-reinnervation and in a demyelinating mouse model of Charcot-Marie-Tooth disease type 1A.

PubMed

Maggs, Alison M; Huxley, Clare; Hughes, Simon M

2008-12-01

Innervation regulates the contractile properties of vertebrate muscle fibers, in part through the effect of electrical activity on expression of distinct myosins. Herein we analyze the role of innervation in regulating the accumulation of the general, maturational, and adult forms of rodent slow myosin heavy chain (MyHC) that are defined by the presence of distinct antigenic epitopes. Denervation increases the number of fibers that express general slow MyHC, but it decreases the adult slow MyHC epitope. Cross-reinnervation of slow muscle by a fast nerve leads to an increase in the number of fibers that express fast MyHC. In both cases, there is an increase in the number of fibers that express slow and fast IIA MyHCs, but without the adult slow MyHC epitope. The data suggest that innervation is required for maturation and maintenance of diversity of both slow and fast fibers. The sequence of slow MyHC epitope transitions is a useful biomarker, and it may play a significant role during nerve-dependent changes in muscle fiber function. We applied this detailed muscle analysis to a transgenic mouse model of human motor and sensory neuropathy IA, also known as Charcot-Marie-Tooth disease type 1A (CMT1A), in which electrical conduction in some motor nerves is poor due to demyelination. The mice display atrophy of some muscle fibers and changes in slow and fast MyHC epitope expression, suggestive of a progressive increase in innervation of muscle fibers by fast motor neurons, even at early stages. The potential role of these early changes in disease pathogenesis is assessed.

Physical-chemical studies of proteins of squid nerve axoplasm, with special reference to the axon fibrous protein.

PubMed

DAVISON, P F; TAYLOR, E W

1960-03-01

The proteins in the axoplasm of the squid, Dosidicus gigas, have been resolved electrophoretically into a major fraction including the fibrous protein, and possibly its structural subunits, and a minor fraction including at least two proteins with low sedimentation coefficients. A partially reversible change in the structure of the fibrous protein occurs under the action of 0.4 M salt or high pH. These experiments have been interpreted to indicate that in the intact fiber one, or a few, protofibrils are arranged helically or longitudinally along the fiber axis, and linked by electrostatic bonds. On the dissociation of these bonds the separated protofibrils assume a less extended form and sediment more rapidly than the intact fibers. Some material with a lower sedimentation rate is also released on the dissociation. This fraction may comprise smaller chain fragments. The volume fraction and the approximate refractive index of the fibers have been calculated.

Physical-Chemical Studies of Proteins of Squid Nerve Axoplasm, with Special Reference to the Axon Fibrous Protein

PubMed Central

Davison, Peter F.; Taylor, Edwin W.

1960-01-01

The proteins in the axoplasm of the squid, Dosidicus gigas, have been resolved electrophoretically into a major fraction including the fibrous protein, and possibly its structural subunits, and a minor fraction including at least two proteins with low sedimentation coefficients. A partially reversible change in the structure of the fibrous protein occurs under the action of 0.4 M salt or high pH. These experiments have been interpreted to indicate that in the intact fiber one, or a few, protofibrils are arranged helically or longitudinally along the fiber axis, and linked by electrostatic bonds. On the dissociation of these bonds the separated protofibrils assume a less extended form and sediment more rapidly than the intact fibers. Some material with a lower sedimentation rate is also released on the dissociation. This fraction may comprise smaller chain fragments. The volume fraction and the approximate refractive index of the fibers have been calculated. PMID:13814536

Otto Friedrich Karl Deiters (1834-1863).

PubMed

Deiters, Vera S; Guillery, R W

2013-06-15

Otto Deiters, for whom the lateral vestibular nucleus and the supporting cells of the outer auditory hair cells were named, died in 1863 aged 29. He taught in the Bonn Anatomy Department, had an appointment in the University Clinic, and ran a small private practice. He published articles on the cell theory, the structure and development of muscle fibers, the inner ear, leukaemia, and scarlet fever. He was the second of five surviving children in an academic family whose private correspondence revealed him to be a young man with limited social skills and high ambitions to complete a deeply original study of the brainstem and spinal cord. However, first his father and then his younger brother died, leaving him and his older brother responsible for a suddenly impecunious family as he failed to gain academic promotion. Otto died of typhus two years after his younger brother's death, leaving his greatest scientific achievement to be published posthumously. He showed that most nerve cells have a single axon and several dendrites; he recognized the possibility that nerve cells might be functionally polarized and produced the first illustrations of synaptic inputs to dendrites from what he termed a second system of nerve fibers. Copyright © 2012 Wiley Periodicals, Inc.

The Effect of Exercise on Neuropathic Symptoms, Nerve Function, and Cutaneous Innervation in People with Diabetic Peripheral Neuropathy

PubMed Central

Kluding, Patricia M.; Pasnoor, Mamatha; Singh, Rupali; Jernigan, Stephen; Farmer, Kevin; Rucker, Jason; Sharma, Neena; Wright, Douglas E.

2012-01-01

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesize that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation. Methods A pre-test post-test design was to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4±5.98; duration of diabetes 12.4±12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. Results Significant reductions in pain (−18.1±35.5 mm on a 100 mm scale, p=0.05), neuropathic symptoms (−1.24±1.8 on MNSI, p=0.01), and increased intraepidermal nerve fiber branching (+0.11±0.15 branch nodes/fiber, p=−.008) from a proximal skin biopsy were noted following the intervention. Conclusions This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies. PMID:22717465

The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy.

PubMed

Kluding, Patricia M; Pasnoor, Mamatha; Singh, Rupali; Jernigan, Stephen; Farmer, Kevin; Rucker, Jason; Sharma, Neena K; Wright, Douglas E

2012-01-01

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesized that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation. A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4±5.98; duration of diabetes 12.4±12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. Significant reductions in pain (-18.1±35.5 mm on a 100 mm scale, P=.05), neuropathic symptoms (-1.24±1.8 on MNSI, P=.01), and increased intraepidermal nerve fiber branching (+0.11±0.15 branch nodes/fiber, P=.008) from a proximal skin biopsy were noted following the intervention. This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Value of a novel PGA-collagen tube on recurrent laryngeal nerve regeneration in a rat model.

PubMed

Suzuki, Hiroshi; Araki, Koji; Matsui, Toshiyasu; Tomifuji, Masayuki; Yamashita, Taku; Kobayashi, Yasushi; Shiotani, Akihiro

2016-07-01

Nerbridge (Toyobo Co., Ltd., Osaka, Japan) is a novel polyglycolic acid (PGA) tube that is filled with collagen fibers and that facilitates nerve fiber expansion and blood vessel growth. It is biocompatible and commercially available, with governmental approval for practical use in Japan. We hypothesized that the PGA-collagen tube would promote regeneration of the recurrent laryngeal nerve (RLN). This hypothesis was examined in a rat axotomy model of the RLN. Prospective animal study. The axotomy model was established by transection of the left RLN in adult Sprague-Dawley rats. The cut ends of the nerve were bridged using Nerbridge (Toyobo Co., Ltd.) with a 1-mm gap (tube-treatment group) or direct sutures (sutured-control group). Left vocal fold mobility, nerve conduction velocity, morphology, and histology were assessed after 15 weeks. Fifteen weeks after treatment, nerve fiber connections were observed macroscopically in both groups, and more clear myelinated fibers and better prevention of laryngeal muscle atrophy were observed in the tube-treatment group compared with the sutured-control group. However, vocal fold movement recovery was not observed in either group, and the conduction velocity of the RLN did not differ between the two groups. Better nerve regeneration was observed in the tube-treatment group. The combination therapy with molecular or gene therapy might be an effective strategy to improve vocal fold movement. The PGA-collagen tube has the potential to promote regeneration of the RLN and to be a scaffold for drug administration in these combination therapies. N/A. Laryngoscope, 126:E233-E239, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

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

NASA Astrophysics Data System (ADS)

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

2011-11-01

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

Anatomy and relations of the infraspinatus and the teres minor muscles: a fresh cadaver dissection study.

PubMed

Bacle, Guillaume; Gregoire, Jean-Marc; Patat, Frédéric; Clavert, Philippe; de Pinieux, Gonzague; Laulan, Jacky; Lakhal, Walid; Favard, Luc

2017-02-01

Despite their functional importance, the infraspinatus (ISP) and teres minor (TM) muscles have been little investigated. This study aimed to describe the macroscopic morphology, innervation, and inter-relations of the ISP and TM muscles. Forty fresh cadaver dissections and histologic analysis were performed. Three groups of specimens were distinguished according to the rotator cuff tendon status: (1) intact rotator cuff; (2) supraspinatus tendon tears with intact ISP tendon; and (3) both supraspinatus and ISP tendons torn. Muscle fiber organization and muscle and tendon length were recorded. ISP and TM innervation and fiber structure were studied. ISP muscles were composed of three groups of fiber organized in two planes: two superficial groups, with mean pennation angles of, respectively, 27° ± 4° and 23° ± 3° with respect to the axis of the central tendon of the underlying group. TMs were thick fusiform muscles showing a parallel organization; 26 specimens (67 %) had aponeuroses isolating the TM, with a mean length of 5.2 ± 2.7 cm. Rotator cuff lesions were associated with relatively greater ISP tendon than muscle length. Innervation of the ISP muscle comprised 2-4 main branches from the suprascapular nerve and that of the TM 1 branch from the axillary nerve. ISP muscle body morphology derives from three groups of fibers in two planes. The TM has a parallel organization. Several nerve branches innervate the ISP muscle, whereas only one supplies the TM. The limits between the two muscles bodies consist of an aponeurotic fascia in two-thirds of cases.

Immunohistologic analysis of spontaneous recurrent laryngeal nerve reinnervation in a rat model.

PubMed

Rosko, Andrew J; Kupfer, Robbi A; Oh, Sang S; Haring, Catherine T; Feldman, Eva L; Hogikyan, Norman D

2018-03-01

After recurrent laryngeal nerve injury (RLN), spontaneous reinnervation of the larynx occurs with input from multiple sources. The purpose of this study was to determine the timing and efficiency of reinnervation across a resected RLN segment in a rat model of RLN injury. Animal study. Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after nerve injury to harvest the larynx and trachea for immunohistologic analysis. The distal RLN segment was stained with neurofilament, and axons were counted and compared to the nonoperated side. Thyroarytenoid (TA) muscles were stained with alpha-bungarotoxin, synaptophysin, and neurofilament to identify intact neuromuscular junctions (NMJ). The number of intact NMJs from the denervated side was compared to the nonoperated side. Nerve fibers regenerated across the resected RLN gap into the distal recurrent laryngeal nerve to innervate the TA muscle. The number of nerve fibers in the distal nerve segment increased over time and reached the normal number by 12 weeks postdenervation. Axons formed intact neuromuscular junctions in the TA, with 48.8% ± 16.7% of the normal number of intact NMJs at 4 weeks and 88.3% ± 30.1% of the normal number by 12 weeks. Following resection of an RLN segment in a rat model, nerve fibers spontaneously regenerate through the distal segment of the transected nerve and form intact NMJs in order to reinnervate the TA muscle. NA. Laryngoscope, 128:E117-E122, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening.

PubMed

Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

2017-09-18

To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes.

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening

PubMed Central

Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

2017-01-01

AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. METHODS Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. RESULTS Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. CONCLUSION Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes. PMID:28979852

ROLE OF TIMING IN ASSESSMENT OF NERVE REGENERATION

PubMed Central

BRENNER, MICHAEL J.; MORADZADEH, ARASH; MYCKATYN, TERENCE M.; TUNG, THOMAS H. H.; MENDEZ, ALLEN B.; HUNTER, DANIEL A.; MACKINNON, SUSAN E.

2014-01-01

Small animal models are indispensable for research on nerve injury and reconstruction, but their superlative regenerative potential may confound experimental interpretation. This study investigated time-dependent neuroregenerative phenomena in rodents. Forty-six Lewis rats were randomized to three nerve allograft groups treated with 2 mg/(kg day) tacrolimus; 5 mg/(kg day) Cyclosporine A; or placebo injection. Nerves were subjected to histomorphometric and walking track analysis at serial time points. Tacrolimus increased fiber density, percent neural tissue, and nerve fiber count and accelerated functional recovery at 40 days, but these differences were undetectable by 70 days. Serial walking track analysis showed a similar pattern of recovery. A ‘blow-through’ effect is observed in rodents whereby an advancing nerve front overcomes an experimental defect given sufficient time, rendering experimental groups indistinguishable at late time points. Selection of validated time points and corroboration in higher animal models are essential prerequisites for the clinical application of basic research on nerve regeneration. PMID:18381659

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

PubMed

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.

Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs.

PubMed

Kanamori, Akiyasu; Nakamura, Makoto; Matsui, Noriko; Nagai, Azusa; Nakanishi, Yoriko; Kusuhara, Sentaro; Yamada, Yuko; Negi, Akira

2004-12-01

To analyze retinal nerve fiber layer (RNFL) thickness in eyes with band atrophy by use of optical coherence tomography (OCT) and to evaluate the ability of OCT to detect this characteristic pattern of RNFL loss. Cross-sectional, retrospective study. Thirty-four eyes of 18 patients with bitemporal hemianopia caused by optic chiasm compression by chiasmal tumors were studied. All eyes were divided into 3 groups according to visual field loss grading after Goldmann perimetry. Retinal nerve fiber layer thickness measurements with OCT. Retinal nerve fiber layer thickness around the optic disc was measured by OCT (3.4-mm diameter circle). Calculation of the changes in OCT parameters, including the horizontal (nasal + temporal quadrant RNFL thickness) and vertical values (superior + inferior quadrant RNFL thickness) was based on data from 160 normal eyes. Comparison between the 3 visual field grading groups was done with the analysis of variance test. The receiver operating characteristic (ROC) curve for the horizontal and vertical value were calculated, and the areas under the curve (AUC) were compared. Retinal nerve fiber layer thickness in eyes with band atrophy decreased in all OCT parameters. The reduction rate in average and temporal RNFL thickness and horizontal value was correlated with visual field grading. The AUC of horizontal value was 0.970+/-0.011, which was significantly different from AUC of vertical value (0.903+/-0.022). The degree of RNFL thickness reduction correlated with that of visual field defects. Optical coherence tomography was able to identify the characteristic pattern of RNFL loss in these eyes.

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

PubMed Central

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 responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463

Spectral Domain Optical Coherence Tomography in Glaucoma: Qualitative and Quantitative Analysis of the Optic Nerve Head and Retinal Nerve Fiber Layer (An AOS Thesis)

PubMed Central

Chen, Teresa C.

2009-01-01

Purpose: To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields. Methods: SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 μm and 3 μm, respectively. Results: Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 μm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003–.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing. Conclusions: To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials. PMID:20126502

ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.

PubMed

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-11-08

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD.

ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density

PubMed Central

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-01-01

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD. PMID:24136731

Poly(D,L-Lactide-Co-Glycolide) Tubes With Multifilament Chitosan Yarn or Chitosan Sponge Core in Nerve Regeneration.

PubMed

Wlaszczuk, Adam; Marcol, Wiesław; Kucharska, Magdalena; Wawro, Dariusz; Palen, Piotr; Lewin-Kowalik, Joanna

2016-11-01

The influence of different kinds of nerve guidance conduits on regeneration of totally transected rat sciatic nerves through a 7-mm gap was examined. Five different types of conduits made of chitosan and poly(D,L-lactide-co-glycolide) (PLGA) were constructed and tested in vivo. We divided 50 animals into equal groups of 10, with a different type of conduit implanted in each group: chitosan sponge core with an average molecular mass of polymer (Mv) of 287 kDa with 7 channels in a PLGA sleeve, chitosan sponge core with an Mv of 423 kDa with 7 channels in a PLGA sleeve, chitosan sponge core (Mv, 423 kDa) with 13 channels in a PLGA sleeve, chitosan multifilament yarn in a PLGA sleeve, and a PLGA sleeve only. Seven weeks after the operation, we examined the distance covered by regenerating nerve fibers, growing of nerves into the conduit's core, and intensity and type of inflammatory reaction in the conduit, as well as autotomy behavior (reflecting neuropathic pain intensity) in the animals. Two types of conduits were allowing nerve outgrowth through the gap with minor autotomy and minor inflammatory reactions. These were the conduits with chitosan multifilament yarn in a PLGA sleeve and the conduits with 13-channel microcrystalline chitosan sponge in a PLGA sleeve. The type of chitosan used to build the nerve guidance conduit influences the intensity and character of inflammatory reaction present during nerve regeneration, which in turn affects the distance crossed by regenerating nerve fibers, growing of the nerve fibers into the conduit's core, and the intensity of autotomy in the animals. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Birefringence imaging directly reveals architectural dynamics of filamentous actin in living growth cones.

PubMed

Katoh, K; Hammar, K; Smith, P J; Oldenbourg, R

1999-01-01

We have investigated the dynamic behavior of cytoskeletal fine structure in the lamellipodium of nerve growth cones using a new type of polarized light microscope (the Pol-Scope). Pol-Scope images display with exquisite resolution and definition birefringent fine structures, such as filaments and membranes, without having to treat the cell with exogenous dyes or fluorescent labels. Furthermore, the measured birefringence of protein fibers in the thin lamellipodial region can be interpreted in terms of the number of filaments in the bundles. We confirmed that birefringent fibers are actin-based using conventional fluorescence-labeling methods. By recording movies of time-lapsed Pol-Scope images, we analyzed the creation and dynamic composition of radial fibers, filopodia, and intrapodia in advancing growth cones. The strictly quantitative information available in time-lapsed Pol-Scope images confirms previously deduced behavior and provides new insight into the architectural dynamics of filamentous actin.

Extraocular Muscles in Patients With Infantile Nystagmus

PubMed Central

Berg, Kathleen T.; Hunter, David G.; Bothun, Erick D.; Antunes-Foschini, Rosalia; McLoon, Linda K.

2013-01-01

Objective To test the hypothesis that the extraocular muscles (EOMs) of patients with infantile nystagmus have muscular and innervational adaptations that may have a role in the involuntary oscillations of the eyes. Methods Specimens of EOMs from 10 patients with infantile nystagmus and postmortem specimens from 10 control subjects were prepared for histologic examination. The following variables were quantified: mean myofiber cross-sectional area, myofiber central nucleation, myelinated nerve density, nerve fiber density, and neuromuscular junction density. Results In contrast to control EOMs, infantile nystagmus EOMs had significantly more centrally nucleated myofibers, consistent with cycles of degeneration and regeneration. The EOMs of patients with nystagmus also had a greater degree of heterogeneity in myofiber size than did those of controls, with no difference in mean myofiber cross-sectional area. Mean myelinated nerve density, nerve fiber density, and neuromuscular junction density were also significantly decreased in infantile nystagmus EOMs. Conclusions The EOMs of patients with infantile nystagmus displayed a distinct hypoinnervated phenotype. This represents the first quantification of changes in central nucleation and myofiber size heterogeneity, as well as decreased myelinated nerve, nerve fiber, and neuromuscular junction density. These results suggest that deficits in motor innervation are a potential basis for the primary loss of motor control. Clinical Relevance Improved understanding of the etiology of nystagmus may direct future diagnostic and treatment strategies. PMID:22411664

Extracellular Recording of Light Responses from Optic Nerve Fibers and the Caudal Photoreceptor in the Crayfish

PubMed Central

Nesbit, Steven C.; Van Hoof, Alexander G.; Le, Chi C.; Dearworth, James R.

2015-01-01

Few laboratory exercises have been developed using the crayfish as a model for teaching how neural processing is done by sensory organs that detect light stimuli. This article describes the dissection procedures and methods for conducting extracellular recording from light responses of both the optic nerve fibers found in the animal’s eyestalk and from the caudal photoreceptor located in the ventral nerve cord. Instruction for ADInstruments’ data acquisition system is also featured for the data collection and analysis of responses. The comparison provides students a unique view on how spike activities measured from neurons code image-forming and non-image-forming processes. Results from the exercise show longer latency and lower frequency of firing by the caudal photoreceptor compared to optic nerve fibers to demonstrate evidence of different functions. After students learn the dissection, recording procedure, and the functional anatomy, they can develop their own experiments to learn more about the photoreceptive mechanisms and the sensory integration of modalities by these light-responsive interneurons. PMID:26557793

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

PubMed

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

2017-01-01

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

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

PubMed Central

Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Brown, Angus M.

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood–brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS). PMID:28798954

Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes

PubMed Central

Cazzato, Daniele; Castori, Marco; Lombardi, Raffaella; Caravello, Francesca; Bella, Eleonora Dalla; Petrucci, Antonio; Grammatico, Paola; Dordoni, Chiara; Colombi, Marina

2016-01-01

Objective: To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS). Methods: Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex- and age-adjusted normative reference values. Results: Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS ≥4 and <7) in 8 patients and severe (NRS ≥7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type. Conclusions: SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS. PMID:27306637

Quantitative magnetic resonance (MR) neurography for evaluation of peripheral nerves and plexus injuries

PubMed Central

Barousse, Rafael; Socolovsky, Mariano; Luna, Antonio

2017-01-01

Traumatic conditions of peripheral nerves and plexus have been classically evaluated by morphological imaging techniques and electrophysiological tests. New magnetic resonance imaging (MRI) studies based on 3D fat-suppressed techniques are providing high accuracy for peripheral nerve injury evaluation from a qualitative point of view. However, these techniques do not provide quantitative information. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are functional MRI techniques that are able to evaluate and quantify the movement of water molecules within different biological structures. These techniques have been successfully applied in other anatomical areas, especially in the assessment of central nervous system, and now are being imported, with promising results for peripheral nerve and plexus evaluation. DWI and DTI allow performing a qualitative and quantitative peripheral nerve analysis, providing valuable pathophysiological information about functional integrity of these structures. In the field of trauma and peripheral nerve or plexus injury, several derived parameters from DWI and DTI studies such as apparent diffusion coefficient (ADC) or fractional anisotropy (FA) among others, can be used as potential biomarkers of neural damage providing information about fiber organization, axonal flow or myelin integrity. A proper knowledge of physical basis of these techniques and their limitations is important for an optimal interpretation of the imaging findings and derived data. In this paper, a comprehensive review of the potential applications of DWI and DTI neurographic studies is performed with a focus on traumatic conditions, including main nerve entrapment syndromes in both peripheral nerves and brachial or lumbar plexus. PMID:28932698

Interventional multispectral photoacoustic imaging with a clinical linear array ultrasound probe for guiding nerve blocks

NASA Astrophysics Data System (ADS)

Xia, Wenfeng; West, Simeon J.; Nikitichev, Daniil I.; Ourselin, Sebastien; Beard, Paul C.; Desjardins, Adrien E.

2016-03-01

Accurate identification of tissue structures such as nerves and blood vessels is critically important for interventional procedures such as nerve blocks. Ultrasound imaging is widely used as a guidance modality to visualize anatomical structures in real-time. However, identification of nerves and small blood vessels can be very challenging, and accidental intra-neural or intra-vascular injections can result in significant complications. Multi-spectral photoacoustic imaging can provide high sensitivity and specificity for discriminating hemoglobin- and lipid-rich tissues. However, conventional surface-illumination-based photoacoustic systems suffer from limited sensitivity at large depths. In this study, for the first time, an interventional multispectral photoacoustic imaging (IMPA) system was used to image nerves in a swine model in vivo. Pulsed excitation light with wavelengths in the ranges of 750 - 900 nm and 1150 - 1300 nm was delivered inside the body through an optical fiber positioned within the cannula of an injection needle. Ultrasound waves were received at the tissue surface using a clinical linear array imaging probe. Co-registered B-mode ultrasound images were acquired using the same imaging probe. Nerve identification was performed using a combination of B-mode ultrasound imaging and electrical stimulation. Using a linear model, spectral-unmixing of the photoacoustic data was performed to provide image contrast for oxygenated and de-oxygenated hemoglobin, water and lipids. Good correspondence between a known nerve location and a lipid-rich region in the photoacoustic images was observed. The results indicate that IMPA is a promising modality for guiding nerve blocks and other interventional procedures. Challenges involved with clinical translation are discussed.

Innervation of taste buds revealed with Brainbow-labeling in mouse.

PubMed

Zaidi, Faisal N; Cicchini, Vanessa; Kaufman, Daniel; Ko, Elizabeth; Ko, Abraham; Van Tassel, Heather; Whitehead, Mark C

2016-12-01

Nerve fibers that surround and innervate the taste bud were visualized with inherent fluorescence using Brainbow transgenic mice that were generated by mating the founder line L with nestin-cre mice. Multicolor fluorescence revealed perigemmal fibers as branched within the non-taste epithelium and ending in clusters of multiple rounded swellings surrounding the taste pore. Brainbow-labeling also revealed the morphology and branching pattern of single intragemmal fibers. These taste bud fibers frequently innervated both the peripheral bud, where immature gemmal cells are located, and the central bud, where mature, differentiated cells are located. The fibers typically bore preterminal and terminal swellings, growth cones with filopodia, swellings, and rounded retraction bulbs. These results establish an anatomical substrate for taste nerve fibers to contact and remodel among receptor cells at all stages of their differentiation, an interpretation that was supported by staining with GAP-43, a marker for growing fibers and growth cones. © 2016 Anatomical Society.

Speckle reduction during all-fiber common-path optical coherence tomography of the cavernous nerves

NASA Astrophysics Data System (ADS)

Chitchian, Shahab; Fiddy, Michael; Fried, Nathaniel M.

2009-02-01

Improvements in identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery, which are responsible for erectile function, may improve nerve preservation and postoperative sexual potency. In this study, we use a rat prostate, ex vivo, to evaluate the feasibility of optical coherence tomography (OCT) as a diagnostic tool for real-time imaging and identification of the cavernous nerves. A novel OCT system based on an all single-mode fiber common-path interferometer-based scanning system is used for this purpose. A wavelet shrinkage denoising technique using Stein's unbiased risk estimator (SURE) algorithm to calculate a data-adaptive threshold is implemented for speckle noise reduction in the OCT image. The signal-to-noise ratio (SNR) was improved by 9 dB and the image quality metrics of the cavernous nerves also improved significantly.

A novel electrospun nerve conduit enhanced by carbon nanotubes for peripheral nerve regeneration

NASA Astrophysics Data System (ADS)

Yu, Wenwen; Jiang, Xinquan; Cai, Ming; Zhao, Wen; Ye, Dongxia; Zhou, Yong; Zhu, Chao; Zhang, Xiuli; Lu, Xiaofeng; Zhang, Zhiyuan

2014-04-01

For artificial nerve conduits, great improvements have been achieved in mimicking the structures and components of autologous nerves. However, there are still some problems in conduit construction, especially in terms of mechanical properties, biomimetic surface tomography, electrical conductivity and sustained release of neurotrophic factors or cells. In this study, we designed and fabricated a novel electrospun nerve conduit enhanced by multi-walled carbon nanotubes (MWNTs) on the basis of a collagen/poly(ɛ-caprolactone) (collagen/PCL) fibrous scaffold. Our aim was to provide further knowledge about the mechanical effects and efficacy of MWNTs on nerve conduits as well as the biocompatibility and toxicology of MWNTs when applied in vivo. The results showed that as one component, carboxyl MWNTs could greatly alter the composite scaffold’s hydrophilicity, mechanical properties and degradability. The electrospun fibers enhanced by MWNTs could support Schwann cell adhesion and elongation as a substrate in vitro. In vivo animal studies demonstrated that the MWNT-enhanced collagen/PCL conduit could effectively promote nerve regeneration of sciatic nerve defect in rats and prevent muscle atrophy without invoking body rejection or serious chronic inflammation. All of these results showed that this MWNT-enhanced scaffold possesses good biocompatibility and MWNTs might be excellent candidates as engineered nanocarriers for further neurotrophic factor delivery research.

Spatial and Functional Selectivity of Peripheral Nerve Signal Recording With the Transversal Intrafascicular Multichannel Electrode (TIME).

PubMed

Badia, Jordi; Raspopovic, Stanisa; Carpaneto, Jacopo; Micera, Silvestro; Navarro, Xavier

2016-01-01

The selection of suitable peripheral nerve electrodes for biomedical applications implies a trade-off between invasiveness and selectivity. The optimal design should provide the highest selectivity for targeting a large number of nerve fascicles with the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME), transversally inserted in the peripheral nerve, has been shown to be useful for the selective activation of subsets of axons, both at inter- and intra-fascicular levels, in the small sciatic nerve of the rat. In this study we assessed the capabilities of TIME for the selective recording of neural activity, considering the topographical selectivity and the distinction of neural signals corresponding to different sensory types. Topographical recording selectivity was proved by the differential recording of CNAPs from different subsets of nerve fibers, such as those innervating toes 2 and 4 of the hindpaw of the rat. Neural signals elicited by sensory stimuli applied to the rat paw were successfully recorded. Signal processing allowed distinguishing three different types of sensory stimuli such as tactile, proprioceptive and nociceptive ones with high performance. These findings further support the suitability of TIMEs for neuroprosthetic applications, by exploiting the transversal topographical structure of the peripheral nerves.

A novel electrospun nerve conduit enhanced by carbon nanotubes for peripheral nerve regeneration.

PubMed

Yu, Wenwen; Jiang, Xinquan; Cai, Ming; Zhao, Wen; Ye, Dongxia; Zhou, Yong; Zhu, Chao; Zhang, Xiuli; Lu, Xiaofeng; Zhang, Zhiyuan

2014-04-25

For artificial nerve conduits, great improvements have been achieved in mimicking the structures and components of autologous nerves. However, there are still some problems in conduit construction, especially in terms of mechanical properties, biomimetic surface tomography, electrical conductivity and sustained release of neurotrophic factors or cells. In this study, we designed and fabricated a novel electrospun nerve conduit enhanced by multi-walled carbon nanotubes (MWNTs) on the basis of a collagen/poly(ε-caprolactone) (collagen/PCL) fibrous scaffold. Our aim was to provide further knowledge about the mechanical effects and efficacy of MWNTs on nerve conduits as well as the biocompatibility and toxicology of MWNTs when applied in vivo.The results showed that as one component, carboxyl MWNTs could greatly alter the composite scaffold's hydrophilicity, mechanical properties and degradability. The electrospun fibers enhanced by MWNTs could support Schwann cell adhesion and elongation as a substrate in vitro. In vivo animal studies demonstrated that the MWNT-enhanced collagen/PCL conduit could effectively promote nerve regeneration of sciatic nerve defect in rats and prevent muscle atrophy without invoking body rejection or serious chronic inflammation. All of these results showed that this MWNT-enhanced scaffold possesses good biocompatibility and MWNTs might be excellent candidates as engineered nanocarriers for further neurotrophic factor delivery research.

Guidance of neurite outgrowth on aligned electrospun polypyrrole/poly(styrene-beta-isobutylene-beta-styrene) fiber platforms.

PubMed

Liu, Xiao; Chen, Jun; Gilmore, Kerry J; Higgins, Michael J; Liu, Yong; Wallace, Gordon G

2010-09-15

The purpose of this work was to investigate the potential biomedical application of novel aligned electrospun polypyrrole (PPy)/poly(styrene-beta-isobutylene-beta-styrene) (SIBS) fibers. After successfully aligning the electroactive PPy/SIBS fibers based on our modified electrospinning method, we demonstrated that neurite outgrowth from PC12 cells could be highly orientated parallel to the aligned PPy/SIBS fibers. Physical interactions between the nerve cells and PPy/SIBS fibers through filopodia "sensing" were observed using atomic force microscopy. These observations indicate a role of contact guidance as a mechanism for the observed alignment. This work highlights the capacity for electroactive PPy/SIBS fibers to support and guide nerve cell differentiation through topographic cues, which is a highly desirable characteristic in medical implants for neurological applications. (c) 2010 Wiley Periodicals, Inc.

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

PubMed

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

2016-11-01

Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0.2ml of 0.5% bupivacaine (n=8) or 0.5% bupivacaine plus 0.005% DEX (n=8) or normal saline (0.9%, as control group) (n=4) in the left hind extremity. Sciatic nerves were harvested at 14days post-injection and analyzed for nerve damage using ultrastructure and histopathologic analysis. Histopathology of sciatic nerve at day 14 post-injection showed a variable degree of neuronal injury associated with perineural inflammation in each treatment group and was classified as none or mild, intermediate or severe. Administration of both LAs resulted in a significant decrease in the total number of myelinated fibers per nerve (95% CI for group difference: Bupivacaine, P=0.001, DEX-Bupivacaine, P=0.036) compared to the saline control group. Animals that received these perineural local anesthetics (LAs) injections showed increased severity of injury compared to the control group. Animals in the DEX-Bupivacaine group had higher perineural inflammation and nerve damage than those of the saline control group and less than those of the Bupivacaine group at day 14 post-injection. Quantitatively, average total nerve fiber per nerve and average myelinated nerve fiber density in the injured region of the Bupivacaine-treated group was less than that of the DEX-Bupivacaine-treated group. LAs injection into the nerve causes peripheral nerve damage and remains an important clinical danger. Bupivacaine is associated with considerable histopathological changes, including edema of the perineurium and myelin degeneration with Wallerian degeneration, when injected perineurally. Perineural DEX added to a clinical concentration of bupivacaine attenuates the Bupivacaine-induced injuries. Copyright © 2016 Elsevier GmbH. All rights reserved.

Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

2014-01-01

The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm.

Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers

PubMed Central

Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

2014-01-01

Objective: The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. Methods: We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Results: Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. Conclusions: The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm. PMID:25210572

Spectral-Domain Optical Coherence Tomography for Glaucoma Diagnosis

PubMed Central

Gracitelli, Carolina P.B; Abe, Ricardo Y; Medeiros, Felipe A

2015-01-01

Identification of structural damage to the optic nerve and retinal nerve fiber layer (RNFL) is an essential component of diagnosis and management of glaucoma. The introduction of spectral-domain OCT (SD-OCT) has allowed objective quantification of damage to these structures with unprecedented resolution. In addition, recent attention has been directed towards imaging the macular area for quantifying loss of neural tissue caused by the disease. Many studies have evaluated and compared the diagnostic accuracies of a variety of parameters that can be obtained from imaging these areas of the ocular fundus. In this article, we critically review the existing literature evaluating the diagnostic accuracy of SD-OCT in glaucoma and we discuss issues related to how SD-OCT results should be incorporated into clinical practice. PMID:26069519

Structure-Function Correlation Using Confocal Laser Ophthalmoscope in Primary Open-Angle Glaucoma and Pseudoexfoliative Glaucoma.

PubMed

Pappas, Theofanis; Founti, Panayiota; Yin, Xiang Jun; Koskosas, Archimidis; Anastasopoulos, Eleftherios; Salonikiou, Angeliki; Kilintzis, Vasilios; Antoniadis, Antonios; Ziakas, Nikolaos; Topouzis, Fotis

2016-04-01

To compare Heidelberg Retina Tomograph (HRT) optic disc parameters and structure-function correlation between primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG). Prospective, observation case series. A total of 54 POAG and 33 PEXG cases, consecutively recruited from a University Glaucoma Service, underwent a comprehensive ophthalmic examination, including HRT optic disc imaging. Glaucoma definition required the presence of both structural and functional damage. One eye per subject was included in the analysis. T test, Mann-Whitney U test, and analysis of covariance were used to compare HRT parameters between POAG and PEXG, adjusting for age, mean deviation (MD) in the visual field, intraocular pressure, and disc area. The correlation between HRT and MD was assessed in each group. Cup area (P=0.048), height variation contour (P=0.016), and cup/disc area ratio (P=0.023) were higher in POAG, whereas the mean retinal nerve fiber layer thickness (P=0.048), retinal nerve fiber layer cross-section area (P=0.044), and rim area (P=0.048) were lower in POAG, compared with PEXG. The correlation of HRT parameters with MD was significant only in the POAG group. At a similar level of functional damage, POAG subjects presented with more pronounced structural damage than PEXG subjects. The correlation between HRT and visual field parameters was more evident in POAG, compared with PEXG.

Normative values for optical coherence tomography parameters in healthy children and interexaminer agreement for choroidal thickness measurements.

PubMed

Turan, Kadriye Erkan; Sekeroglu, Hande Taylan; Baytaroglu, Ata; Bezci, Figen; Karahan, Sevilay

2018-01-01

To (a) determine the normative values for optical coherence tomography (OCT) parameters such as central macular thickness, retinal nerve fiber layer thickness, and choroidal thickness in healthy children; (b) investigate the relationships of these parameters with axial length, central corneal thickness, refractive errors, and intraocular pressure; and (c) determine interexaminer agreement for choroidal thickness measurements. In this cross-sectional study, 120 healthy children aged 8-15 years underwent detailed ophthalmological examination and OCT measurements. Choroidal thickness was measured at three separate locations by two independent examiners. The mean global retinal nerve fiber layer thickness was 98.75 ± 9.45 μm (79.0-121.0). The mean central macular thickness was 232.29 ± 29.37 μm (190.0-376.0). The mean subfoveal choroidal thickness obtained by examiner 1 was 344.38 ± 68.83 μm and that obtained by examiner 2 was 344.04 ± 68.92 μm. Interexaminer agreement was between 99.6%-99.8% for choroidal thickness at three separate locations. Central macular thickness increased with axial length (r=0.245, p=0.007). Choroidal thickness increased with age (r=0.291, p=0.001) and decreased with axial length (r=-0.191, p=0.037). Global retinal nerve fiber layer thickness decreased with axial length (r=-0.247, p=0.007) and increased with central corneal thickness (r=0.208, p=0.022). Global retinal nerve fiber layer thickness positively correlated with choroidal thickness (r=0.354, p<0.001). Global retinal nerve fiber layer thickness (r=0.223, p=0.014) and choroidal thickness (r=0.272, p=0.003) increased with the spherical equivalent (D). Optical coherence tomography parameters showed a wide range of variability in children. Retinal nerve fiber layer thickness, central macular thickness, and choroidal thickness were found to be either inter-related or correlated with age, central corneal thickness, axial length, and refractive errors. Furthermore, manual measurements of choroidal thickness showed high interexaminer agreement. Because normative values for optical coherence tomography parameters differed in children, the measurements should be interpreted according to an age-appropriate database.

Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study.

PubMed

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).

Angiographic and structural imaging using high axial resolution fiber-based visible-light OCT

PubMed Central

Pi, Shaohua; Camino, Acner; Zhang, Miao; Cepurna, William; Liu, Gangjun; Huang, David; Morrison, John; Jia, Yali

2017-01-01

Optical coherence tomography using visible-light sources can increase the axial resolution without the need for broader spectral bandwidth. Here, a high-resolution, fiber-based, visible-light optical coherence tomography system is built and used to image normal retina in rats and blood vessels in chicken embryo. In the rat retina, accurate segmentation of retinal layer boundaries and quantification of layer thicknesses are accomplished. Furthermore, three distinct capillary plexuses in the retina and the choriocapillaris are identified and the characteristic pattern of the nerve fiber layer thickness in rats is revealed. In the chicken embryo model, the microvascular network and a venous bifurcation are examined and the ability to identify and segment large vessel walls is demonstrated. PMID:29082087

Potential Role of In Vivo Confocal Microscopy for Imaging Corneal Nerves in Transthyretin Familial Amyloid Polyneuropathy.

PubMed

Rousseau, Antoine; Cauquil, Cecile; Dupas, Benedicte; Labbé, Antoine; Baudouin, Christophe; Barreau, Emmanuel; Théaudin, Marie; Lacroix, Catherine; Guiochon-Mantel, Anne; Benmalek, Anouar; Labetoulle, Marc; Adams, David

2016-09-01

Small fiber neuropathy (SFN) is an important feature of transthyretin familial amyloid polyneuropathy (TTR-FAP). A practical and objective method for the clinical evaluation of SFN is needed to improve the management of this disease. In vivo confocal microscopy (IVCM) of the corneal nerves, a rapid noninvasive technique, may be used as a surrogate marker of SFN. To determine the correlation of SFN with IVCM in patients with TTR-FAP. A prospective, single-center, cross-sectional controlled study was conducted at the French National Reference Center for TTR-FAP from June 1, 2013, to June 30, 2014. Fifteen patients with TTR-FAP underwent a complete neurologic examination, including Neuropathy Impairment Score of the Lower Limbs, hand grip strength, and evaluation of vegetative dysfunction, as well as electrophysiologic studies (nerve conduction and electrochemical skin conductance) and intraepidermal nerve fiber density quantification. Patients and 15 controls (matched for age and sex) underwent ophthalmologic assessments, including corneal esthesiometry and IVCM. Correlation of corneal nerve fiber length (CNFL) with the severity of SFN. Of the 15 patients enrolled in the study, 6 were women (40%); mean (SD) age was 54.4 [13.7] years. The CNFL was shorter in the patients than in controls (13.08 vs 17.57 mm/mm2; difference of 4.49 [95% CI, 0.72 to 8.27]; P = .02). The patients' CNFL correlated with the severity of both autonomic neuropathy assessed by the Compound Autonomic Dysfunction Test (rs = 0.66 [95% CI, 0.22 to 0.87]; P = .008) or electrochemical skin conductance (rs = 0.80 [95% CI, 0.50 to 0.93]; P < .001) and sensorimotor neuropathy assessed using the Neuropathy Impairment Score of the Lower Limbs (rs = -0.58 [95% CI, -0.84 to -0.11]; P = .02). Patients with altered sensory nerve action potentials and intraepidermal nerve fiber density had a shorter CNFL (P = .04 and P = .02, respectively). The CNFL could be measured in all patients compared with sensory nerve action potentials (11 patients [73%; 95% CI, 44% to 92%]; P < .001) and intraepidermal nerve fiber density (4 patients [27%; 95% CI, 8% to 55%]; P < .001). In these 15 patients with TTR-FAP, IVCM measurement permitted rapid, noninvasive evaluation of small-fiber alterations in patients and could be used to assess SFN in this setting. The CNFL could be measured in all patients, thus avoiding the floor effect seen with other neuropathy measures. Longitudinal studies with more cases evaluated are needed to define the place of IVCM in monitoring patients with TTR-FAP.

Morphological evidence for local microcircuits in rat vestibular maculae

NASA Technical Reports Server (NTRS)

Ross, M. D.

1997-01-01

Previous studies suggested that intramacular, unmyelinated segments of vestibular afferent nerve fibers and their large afferent endings (calyces) on type I hair cells branch. Many of the branches (processes) contain vesicles and are presynaptic to type II hair cells, other processes, intramacular nerve fibers, and calyces. This study used serial section transmission electron microscopy and three-dimensional reconstruction methods to document the origins and distributions of presynaptic processes of afferents in the medial part of the adult rat utricular macula. The ultrastructural research focused on presynaptic processes whose origin and termination could be observed in a single micrograph. Results showed that calyces had 1) vesiculated, spine-like processes that invaginated type I cells and 2) other, elongate processes that ended on type II cells pre- as well as postsynaptically. Intramacular, unmyelinated segments of afferent nerve fibers gave origin to branches that were presynaptic to type II cells, calyces, calyceal processes, and other nerve fibers in the macula. Synapses with type II cells occurred opposite subsynaptic cisternae (C synapses); all other synapses were asymmetric. Vesicles were pleomorphic but were differentially distributed according to process origin. Small, clear-centered vesicles, approximately 40-60 nm in diameter, predominated in processes originating from afferent nerve fibers and basal parts of calyces. Larger vesicles approximately 70-120 nm in diameter having approximately 40-80 nm electron-opaque cores were dominant in processes originating from the necks of calyces. Results are interpreted to indicate the existence of a complex system of intrinsic feedforward (postsynaptic)-feedback (presynaptic) connections in a network of direct and local microcircuits. The morphological findings support the concept that maculae dynamically preprocess linear acceleratory information before its transmission to the central nervous system.

Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release?

PubMed

Seyedi, N; Maruyama, R; Levi, R

1999-08-01

We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.

Scanning electron microscopy of echinoid podia.

PubMed

Florey, E; Cahill, M A

1982-01-01

Tube feet of the sea urchin Strongylocentrotus franciscanus were studied with the scanning electron microscope (SEM). By use of fractured preparations it was possible to obtain views of all components of the layered tube-foot wall. The outer epithelium was found to bear tufts of cilia possibly belonging to sensory cells. The nerve plexus was clearly revealed as being composed of bundles of varicose axons. The basal lamina, which covers the outer and inner surfaces of the connective tissue layer, was found to be a mechanically resistant and elastic membrane. The connective tissue appears as dense bundles of (collagen) fibers. The luminal epithelium (coelothelium) is a single layer of flagellated collar cells. There is no indication that the muscle fibers, which insert on the inner basal lamina of the connective tissue layer are innervated by axons from the basi-epithelial nerve plexus. The results agree with previous conclusions concerning tube-foot structure based on transmission electron microscopy, and provide additional information, particularly with regard to the outer and inner epithelia.

Differential effects of myostatin deficiency on motor and sensory axons.

PubMed

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.

Cold Exposure Exacerbates the Development of Diabetic Polyneuropathy in the Rat

PubMed Central

Kasselman, Lora J.; Veves, Aristidis; Gibbons, Christopher H.; Rutkove, Seward B.

2009-01-01

Diabetic polyneuropathy (DPN) and cold-induced nerve injury share several pathogenic mechanisms. This study explores whether cold exposure contributes to the development of DPN. Streptozotocin-induced diabetic rats and controls were exposed to a room temperature (23°C) or cold environment (10°C). H-reflex, tail and sciatic motor, and sensory nerve conduction studies were performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold environment had an increased H-reflex four weeks earlier than diabetic room temperature animals (P = .03). Cold-exposed diabetic animals also had greater reduction in motor conduction velocities at 20 weeks (P = .017), decreased skin nerve fiber density (P = .037), and increased skin nitrotyrosine levels (P = .047). Cold exposure appears to hasten the development of DPN in the rat STZ model of diabetes. These findings support that further study into the relationship between ambient temperature and DPN is warranted. PMID:20130819

The Functional Anatomy of Nerves Innervating the Ventral Grooved Blubber of Fin Whales (Balaenoptera Physalus).

PubMed

Vogl, Wayne; Petersen, Hannes; Adams, Arlo; Lillie, Margo A; Shadwick, Robert E

2017-11-01

Nerves that supply the floor of the oral cavity in rorqual whales are extensible to accommodate the dramatic changes in tissue dimensions that occur during "lunge feeding" in this group. We report here that the large nerves innervating the muscle component of the ventral grooved blubber (VGB) in fin whales are branches of cranial nerve VII (facial nerve). Therefore, the muscles of the VGB are homologous to second branchial arch derived muscles, which in humans include the muscles of "facial expression." We speculate, based on the presence of numerous foramina on the dorsolateral surface of the mandibular bones, that general sensation from the VGB likely is carried by branches of the mandibular division (V3) of cranial nerve V (trigeminal nerve), and that these small branches travel in the lipid-rich layer directly underlying the skin. We show that intercostal and phrenic nerves, which are not extensible, have a different wall and nerve core morphology than the large VGB nerves that are branches of VII. Although these VGB nerves are known to have two levels of waviness, the intercostal and phrenic nerves have only one in which the nerve fascicles in the nerve core are moderately wavy. In addition, the VGB nerves have inner and outer parts to their walls with numerous large elastin fibers in the outer part, whereas intercostal and phrenic nerves have single walls formed predominantly of collagen. Our results illustrate that overall nerve morphology depends greatly on location and the forces to which the structures are exposed. Anat Rec, 300:1963-1972, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

PubMed

Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

2011-01-01

A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

Analysis of compound action potentials elicited with specific current stimulating pulses in an isolated rat sciatic nerve.

PubMed

Žužek, Monika C; Rozman, Janez; Pečlin, Polona; Vrecl, Milka; Frangež, Robert

2017-02-01

The ability to selectively stimulate Aα, Aβ-fibers and Aδ-fibers in an isolated rat sciatic nerve (SNR) was assessed. The stimulus used was a current, biphasic pulse with a quasitrapezoidal cathodic phase and rectangular anodic phase where parameters were systematically varied: intensity of the cathodic phase (ic); width of the cathodic phase (tc); width of the cathodic exponential decay (texp) and time constant of the exponential decay (τexp). A SNR was stimulated using a pair of hook electrodes while conduction velocity (CV) and compound action potentials (CAP) were measured at two sites along the SNR using another two pairs of electrodes. Results showed that the highest CAP1 (8.5-9 mV), shall be expected when parameters of the stimulus were within the following range: ic=3.8-4 mA, tc=350-400 μs and texp=330-440 μs. Results also showed that with ascending tc and texp, CV of the corresponding superficial region of the SNR was reduced in both, conduction velocity of CAP1 and conduction velocity of CAP2. It was concluded that action potentials (APs) were activated in the Aβ-fibers and Aδ-fibers along with a slight AP inhibition in the Aβ-fibers. The obtained results, could serve as a tool for developing multi-electrode systems that potentially enable fiber-type selective stimulation of nerve fibers.

Three-dimensional cell shapes and arrangements in human sweat glands as revealed by whole-mount immunostaining

PubMed Central

Kurata, Ryuichiro; Futaki, Sugiko; Nakano, Itsuko; Fujita, Fumitaka; Tanemura, Atsushi; Murota, Hiroyuki; Katayama, Ichiro; Okada, Fumihiro

2017-01-01

Because sweat secretion is facilitated by mechanical contraction of sweat gland structures, understanding their structure-function relationship could lead to more effective treatments for patients with sweat gland disorders such as heat stroke. Conventional histological studies have shown that sweat glands are three-dimensionally coiled tubular structures consisting of ducts and secretory portions, although their detailed structural anatomy remains unclear. To better understand the details of the three-dimensional (3D) coiled structures of sweat glands, a whole-mount staining method was employed to visualize 3D coiled gland structures with sweat gland markers for ductal luminal, ductal basal, secretory luminal, and myoepithelial cells. Imaging the 3D coiled gland structures demonstrated that the ducts and secretory portions were comprised of distinct tubular structures. Ductal tubules were occasionally bent, while secretory tubules were frequently bent and formed a self-entangled coiled structure. Whole-mount staining of complex coiled gland structures also revealed the detailed 3D cellular arrangements in the individual sweat gland compartments. Ducts were composed of regularly arranged cuboidal shaped cells, while secretory portions were surrounded by myoepithelial cells longitudinally elongated along entangled secretory tubules. Whole-mount staining was also used to visualize the spatial arrangement of blood vessels and nerve fibers, both of which facilitate sweat secretion. The blood vessels ran longitudinally parallel to the sweat gland tubules, while nerve fibers wrapped around secretory tubules, but not ductal tubules. Taken together, whole-mount staining of sweat glands revealed the 3D cell shapes and arrangements of complex coiled gland structures and provides insights into the mechanical contraction of coiled gland structures during sweat secretion. PMID:28636607

[Functional anatomy of the cochlear nerve and the central auditory system].

PubMed

Simon, E; Perrot, X; Mertens, P

2009-04-01

The auditory pathways are a system of afferent fibers (through the cochlear nerve) and efferent fibers (through the vestibular nerve), which are not limited to a simple information transmitting system but create a veritable integration of the sound stimulus at the different levels, by analyzing its three fundamental elements: frequency (pitch), intensity, and spatial localization of the sound source. From the cochlea to the primary auditory cortex, the auditory fibers are organized anatomically in relation to the characteristic frequency of the sound signal that they transmit (tonotopy). Coding the intensity of the sound signal is based on temporal recruitment (the number of action potentials) and spatial recruitment (the number of inner hair cells recruited near the cell of the frequency that is characteristic of the stimulus). Because of binaural hearing, commissural pathways at each level of the auditory system and integration of the phase shift and the difference in intensity between signals coming from both ears, spatial localization of the sound source is possible. Finally, through the efferent fibers in the vestibular nerve, higher centers exercise control over the activity of the cochlea and adjust the peripheral hearing organ to external sound conditions, thus protecting the auditory system or increasing sensitivity by the attention given to the signal.

Blood pressure control with selective vagal nerve stimulation and minimal side effects

NASA Astrophysics Data System (ADS)

Plachta, Dennis T. T.; Gierthmuehlen, Mortimer; Cota, Oscar; Espinosa, Nayeli; Boeser, Fabian; Herrera, Taliana C.; Stieglitz, Thomas; Zentner, Joseph

2014-06-01

Objective. Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. Approach. We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. Main results. Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. Significance. The presented method is robust to impedance changes, independent of the electrode's relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

Fiber optics in composite materials: materials with nerves of glass

NASA Astrophysics Data System (ADS)

Measures, Raymond M.

1990-08-01

A Fiber Optic BasedSmart Structure wiipossess a structurally integrated optical microsensor system for determining its state. This built-in sensor system should, in real-time, be able to: evaluate the strain or deformation of a structure, monitor if its vibrating or subject to excessive loads, check its temperature and warn of the appearance of any hot spots. In addition a Smart Structure should maintain a vigilant survelliance over its structural integrity. The successful development of Smart StructureTechnolgy could lead to: aircraft that are safer, lighter, more efficient, easier to maintain and to service; pipelines, pressure vessels and storage tanks that constantly monitor their structuralintegrity and immediately issue an alert ifany problem is detected; space platforms that check forpressure leaks, unwanted vibration, excess thermal buildup, and deviation from some preassigned shape.This technology is particularly appropriate for composite materials where internal damage generated by: impacts, manufacturing flaws, excessive loading or fatigue could be detected and assessed. In service monitoring of structural loads, especially in regions like wing roots of aircraft, could be ofconsiderable benefit in helping to avoid structural overdesign and reduce weight. Structurally imbedded optical fibers sensors might also serve to monitor the cure state of composite thermosets during their fabrication and thereby contribute to improved quality control of these products.

Evaluation of specific neural marker GAP-43 and TH combined with Masson-trichrome staining for forensic autopsy cases with old myocardial infarction.

PubMed

Yu, Tian-Shui; Wang, Xu; Zhang, Hai-Dong; Bai, Ru-Feng; Zhao, Rui; Guan, Da-Wei

2018-01-01

It has been a puzzling forensic task to determine the cause of death as a result of old myocardial infarction (OMI) in the absence of recognizable acute myocardial infarction. Recent studies indicated that the heterogeneous cardiac nerve sprouting and sympathetic hyperinnervation at border zones of the infarcted site played important roles in sudden cardiac death (SCD). So, the present study explored the value of growth associated protein-43 (GAP-43) and tyrosine hydroxylase (TH) as objective and specific neural biomarkers combined with Masson-trichrome staining for forensic autopsy cases. Myocardium of left ventricle of 58 medicolegal autopsy cases, 12 OMI cases, 12 acute/OMI cases, and 34 control cases, were immunostained with anti-GAP-43 and anti-TH antibodies. Immunoreactivity of GAP-43 and TH identified nerve fibers and vascular wall in OMI cases and acute/OMI cases. Specifically, TH-positive nerve fibers were abundant at border zones of the infarcted site. There were a few GAP-43 and TH expressions in the control cases. With Masson-trichrome staining, collagen fibers were blue and cardiac muscle fibers were pink in marked contrast with the surrounding tissue, which improved the location of nerve fibers. Thus, these findings suggest that immunohistochemical detection of GAP-43 and TH combined with Masson-trichrome staining can provide the evidence for the medicolegal expertise of SCD due to OMI, and further demonstrate a close relationship between sympathetic hyperinnervation and SCD.

Neuroanatomical study of Galen's anastomosis (nervus laryngeus) in the dog.

PubMed

Henry, C; Cazals, Y; Gioux, M; Didier, A; Aran, J M; Traissac, L

1988-01-01

To further knowledge of the laryngeal nerves, the nerve fibers of Galen's anastomosis were studied using two neuroanatomical methods, namely nerve degeneration and horseradish peroxidase labeling. It is demonstrated that the superior laryngeal nerve forms part of the tracheal and esophageal nervous system. The value of the results in relation to physiological laryngeal studies and to human laryngeal diseases is discussed.

Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain.

PubMed

Inoue, Makoto; Yamaguchi, Asuka; Kawakami, Megumi; Chun, Jerold; Ueda, Hiroshi

2006-08-16

Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.

Energy-optimal electrical excitation of nerve fibers.

PubMed

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.

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

PubMed

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.

Reflectance Speckle of Retinal Nerve Fiber Layer Reveals Axonal Activity

PubMed Central

Huang, Xiang-Run; Knighton, Robert W.; Zhou, Ye; Zhao, Xiao-Peng

2013-01-01

Purpose. This study investigated the retinal nerve fiber layer (RNFL) reflectance speckle and tested the hypothesis that temporal change of RNFL speckle reveals axonal dynamic activity. Methods. RNFL reflectance speckle of isolated rat retinas was studied with monochromatic illumination. A series of reflectance images was collected every 5 seconds for approximately 15 minutes. Correlation coefficients (CC) of selected areas between a reference and subsequent images were calculated and plotted as a function of the time intervals between images. An exponential function fit to the time course was used to evaluate temporal change of speckle pattern. To relate temporal change of speckle to axonal activity, in vitro living retina perfused at a normal (34°C) and a lower (24°C) temperature, paraformaldehyde-fixed retina, and retina treated with microtubule depolymerization were used. Results. RNFL reflectance was not uniform; rather nerve fiber bundles had a speckled texture that changed with time. In normally perfused retina, the time constant of the CC change was 0.56 ± 0.26 minutes. In retinas treated with lower temperature and microtubule depolymerization, the time constants increased by two to four times, indicating that the speckle pattern changed more slowly. The speckled texture in fixed retina was stationary. Conclusions. Fixation stops axonal activity; treatments with either lower temperature or microtubule depolymerization are known to decrease axonal transport. The results obtained in this study suggest that temporal change of RNFL speckle reveals structural change due to axonal activity. Assessment of RNFL reflectance speckle may offer a new means of evaluating axonal function. PMID:23532525

Optical path of infrared neural stimulation in the guinea pig and cat cochlea

NASA Astrophysics Data System (ADS)

Rajguru, Suhrud M.; Hwang, Margaret; Moreno, Laura E.; Matic, Agnella I.; Stock, Stuart R.; Richter, Claus-Peter

2011-03-01

It has been demonstrated previously that infrared neural stimulation (INS) can be used to stimulate spiral ganglion cells in the cochlea. With INS, neural stimulation can be achieved without direct contact of the radiation source and the tissue and is spatially well resolved. The presence of fluids or bone between the target structure and the radiation source may lead to absorption or scattering of the radiation and limit the efficacy of INS. To develop INS based cochlear implants, it is critical to determine the beam path of the radiation in the cochlea. In the present study, we utilized noninvasive X-ray microtomography (microCT) to visualize the orientation and location of the optical fiber within the guinea pig and cat cochlea. Overall, the results indicated that the optical fiber was directed towards the spiral ganglion cells in the cochlea and not the nerve fibers in the center of the modiolus. The fiber was approximately 300 μm away from the target structures. In future studies, results from the microCT will be correlated with physiology obtained from recordings in the midbrain.

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

NASA Astrophysics Data System (ADS)

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

2013-07-01

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

Recent clinical advances in diabetic polyneuropathy.

PubMed

Horowitz, Steven H

2006-10-01

Recent dramatic increases in the incidence and prevalence of diabetes make an understanding of chronic symmetric sensorimotor diabetic polyneuropathy, the most common and problematic of chronic diabetic complications, essential for a wide range of medical practitioners. The demonstration of neuropathic dysfunction in patients with prediabetes or impaired glucose tolerance emphasizes the susceptibility of peripheral nerve fibers, especially small A delta fibers and C fibers, to relatively mild, short-duration hyperglycemia. New testing can reveal peripheral nerve dysfunction prior to clinical neuropathic symptoms and signs. In the absence of effective medications to halt or reverse nerve damage or promote nerve regeneration, early diagnosis of diabetic polyneuropathy, followed by tight glycemic control with diet and exercise, offers the best opportunity to prevent progressive symptoms of sensory loss, pain, autonomic dysfunction, ulcerations, and amputations. Some patients with impaired glucose tolerance have a reversal of neuropathic features with tight glycemic control. Nonpharmacologic therapies for neuropathic pain in diabetic polyneuropathy appear promising. Tight glycemic control, especially early in diabetes, is the best approach to minimizing the prevalence and severity of diabetic polyneuropathy and makes research into the deleterious effects of even mild hyperglycemia imperative.

[Clinical evaluation of the optic disc in glaucoma].

PubMed

Greslechner, R; Spiegel, D

2016-10-01

Glaucoma is defined as a progressive neuropathy of the optic nerve, characterized by specific changes of the optic disc, parapapillary region, and retinal nerve fiber layer. Characteristic glaucomatous changes of the optic disc, parapapillary region, and retinal nerve fiber layer are discussed and their ophthalmoscopic examination is described. A literature search in the PubMed database was conducted. A systematic step-by-step approach to a qualitative and quantitative ophthalmoscopic evaluation of the optic disc regarding glaucomatous damage is presented. A systematic, clinical, qualitative, and quantitative assessment of the optic disc can be performed with little effort and forms the basis for diagnosis and treatment of glaucoma.

[Morphological substrate and pathogenetic mechanisms of pelvic pain syndrome in endometriosis. Part II. Peripheral nerve tissue remodeling in the foci of endometriosis].

PubMed

Kogan, E A; Ovakimyan, A S; Paramonova, N B; Faizullina, N M; Kazachenko, I F; Adamyan, L V

2016-01-01

Endometriosis (EM) is morphologically characterized by the development of extrauterine endometrioid heterotopies, the major clinical symptoms of which is chronic pelvic pain, which is a serious problem not only in modern gynecology, but also in public health as a whole. to investigate neurogenic markers in the foci of EM of various sites and histological structure in women with and without pain syndrome. The investigation was performed using the operative material (resected segments of the intestine, bladder, rectovaginal septum, and small pelvic peritoneum) obtained from 52 women with an intraoperative and morphologically verified diagnosis of EM and (Group 1) and without (Group 2) pain syndrome. Immunohistochemical examination was made on paraffin-embedded tissue sections in accordance with the standard protocols, by using the antibodies: 1) anti-PGP 9.5 polyclonal rabbit antibodies; 2) mouse anti-human neurofilament (NF) protein monoclonal antibodies (Clone 2F1); 3) mouse anti-nerve growth factor (NGF) monoclonal antibodies; 4) monoclonal mouse anti-human NGF receptor p75 (NGFRp75) antibodies (Dako, Denmark). Our findings demonstrate differences in the expression of PGP 9.5, NFs, NGF, and NGFRp75 in the foci and adjacent tissue in painful and painless EM irrespective of the locations of heterotopies. The found molecular features are a manifestation of the remodeling of nerve fibers and nerve endings in the foci of EM and PGP9.5, NGF, and NGFRp75 give rise to nerve fiber neoformation and pain syndrome in EM. At the same time, the immunohistochemical phenotype of EM foci does not depend on their site and reflects the presence or absence of pain syndrome.

The Parameters of Transcutaneous Electrical Nerve Stimulation Are Critical to Its Regenerative Effects When Applied Just after a Sciatic Crush Lesion in Mice

PubMed Central

Martins Lima, Êmyle; Teixeira Goes, Bruno; Zugaib Cavalcanti, João; Vannier-Santos, Marcos André; Martinez, Ana Maria Blanco; Baptista, Abrahão Fontes

2014-01-01

We investigated the effect of two frequencies of transcutaneous electrical nerve stimulation (TENS) applied immediately after lesion on peripheral nerve regeneration after a mouse sciatic crush injury. The animals were anesthetized and subjected to crushing of the right sciatic nerve and then separated into three groups: nontreated, Low-TENS (4 Hz), and High-TENS (100 Hz). The animals of Low- and High-TENS groups were stimulated for 2 h immediately after the surgical procedure, while the nontreated group was only positioned for the same period. After five weeks the animals were euthanized, and the nerves dissected bilaterally for histological and histomorphometric analysis. Histological assessment by light and electron microscopy showed that High-TENS and nontreated nerves had a similar profile, with extensive signs of degeneration. Conversely, Low-TENS led to increased regeneration, displaying histological aspects similar to control nerves. High-TENS also led to decreased density of fibers in the range of 6–12 μm diameter and decreased fiber diameter and myelin area in the range of 0–2 μm diameter. These findings suggest that High-TENS applied just after a peripheral nerve crush may be deleterious for regeneration, whereas Low-TENS may increase nerve regeneration capacity. PMID:25147807

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

PubMed

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.

The Effects of the Air Cast Sports Stirrup on Postural Sway in Normal Males

DTIC Science & Technology

1993-01-01

Pittsburgh Pittsburgh, PAI Paula Sammarone, MA, ATC Date Rangos School of Health Sciences I Director, Athletic Training Duquesne University I Pittsburgh, PA I...sprain occurs, tearing of the ligaments also occur, which results in de- afferentization of the articular nerves (20). 1 Several treatment modalities...intermediate ranges. Articular nerve fibers have lower tensile strength than collagen fibers (21). Since most inversion injuries of the ankle result in some

Ocular toxocariasis presenting as bilateral scleritis with suspect retinal granuloma in the nerve fiber layer: a case report.

PubMed

Pak, Kang Yeun; Park, Sung Who; Byon, Ik Soo; Lee, Ji Eun

2016-08-18

This report details ocular toxocariasis presenting as bilateral scleritis with suspect retinal granuloma in the nerve fiber layer. The patient presented with scleritis, which did not improve with systemic steroid. Intraocular pressure was elevated, and well demarcated hyper-reflective round lesion were noted in both eyes. He had a history of general ache and concurrent onset of ocular symptoms the day after eating raw meat. Systemic work-ups revealed no remarkable abnormalities except antibody for toxocara. Oral albendazole and steroid were prescribed. The inflammation and swellings resolved without recurrence. In the current case, scleritis with suspect granuloma in the nerve fiber layer seems to be caused by toxocara. Ocular toxocariasis can be presented as atypical features. Serologic exams for toxocariasis would be considered not only in typical features but also in other uveitis or scleritis, particularly when the patient has a related history.

Neurogenic vasodilatation and plasma leakage in the skin.

PubMed

Holzer, P

1998-01-01

1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.

Anatomy and histology of the transverse humeral ligament.

PubMed

Snow, Brian J; Narvy, Steven J; Omid, Reza; Atkinson, Roscoe D; Vangsness, C Thomas

2013-10-01

The classic literature describes the transverse humeral ligament (THL) as a distinct anatomic structure with a role in biceps tendon stability; however, recent literature suggests that it is not a distinct anatomic structure. The purpose of this study was to evaluate the gross and microscopic anatomy of the THL, including a specific investigation of the histology of this ligament. Thirty frozen, embalmed cadaveric specimens were dissected to determine the gross anatomy of the THL. Seven specimens were evaluated histologically for the presence of mechanoreceptors and free nerve endings. Two tissue layers were identified in the area described as the THL. In the deep layer, fibers of the subscapularis tendon were found to span the bicipital groove with contributions from the coracohumeral ligament and the supraspinatus tendon. Superficial to this layer was a fibrous fascial covering consisting of distinct bands of tissue. Neurohistology staining revealed the presence of free nerve endings but no mechanoreceptors. This study's findings demonstrate that the THL is a distinct structure continuous with the rotator cuff tendons and the coracohumeral ligament. The finding of free nerve endings in the THL suggests a potential role as a shoulder pain generator. Copyright 2013, SLACK Incorporated.

Electrophysiologic identification of the cochlear nerve fibers during cerebello-pontine angle surgery.

PubMed

Colletti, V; Fiorino, F G

1993-11-01

To facilitate identification and preservation of the auditory nerve during cerebello-pontine angle surgery, bipolar recording of cochlear nerve compound action potentials (CNAPs) was performed. Two silver wires insulated with teflon up to the exposed ends were utilized as electrodes. They were twisted together, the distance between the two tips being 1 mm or less. Rarefaction polarity clicks (31/s) ranging from the psychoacoustical threshold to 120 dB pe SPL were used as stimuli. The investigation was performed in three groups of patients. The first group consisted of 9 patients submitted to vestibular neurectomy and 4 patients operated on by microvascular decompression of the eighth nerve. The second group comprised 8 patients with acoustic tumors smaller than 2 mm and serviceable hearing. Postoperative audiometric results in the subjects in the second group were compared with those obtained in well-matched homogeneous controls consisting of patients with acoustic neuroma operated on without the aid of CNAP recording. Bipolar recording from the eighth nerve was extremely selective, a good response being obtained only when positioning the electrode on the cochlear portion of the eighth nerve. During removal of the acoustic neuroma, repeated bipolar probing of the tumor and eighth nerve facilitated the task of distinguishing the cochlear nerve from other nervous structures and from the tumor, and contributed to preserving hearing in most patients.

Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients.

PubMed

Sakamoto, Junya; Manabe, Yoshitaka; Oyamada, Joichi; Kataoka, Hideki; Nakano, Jiro; Saiki, Kazunobu; Okamoto, Keishi; Tsurumoto, Toshiyuki; Okita, Minoru

2018-07-01

Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705-709, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Multiscale Poly-(ϵ-caprolactone) Scaffold Mimicking Nonlinearity in Tendon Tissue Mechanics

PubMed Central

Banik, Brittany L.; Lewis, Gregory S.; Brown, Justin L.

2016-01-01

Regenerative medicine plays a critical role in the future of medicine. However, challenges remain to balance stem cells, biomaterial scaffolds, and biochemical factors to create successful and effective scaffold designs. This project analyzes scaffold architecture with respect to mechanical capability and preliminary mesenchymal stem cell response for tendon regeneration. An electrospun fiber scaffold with tailorable properties based on a “Chinese-fingertrap” design is presented. The unique criss-crossed fiber structures demonstrate non-linear mechanical response similar to that observed in native tendon. Mechanical testing revealed that optimizing the fiber orientation resulted in the characteristic “S”-shaped curve, demonstrating a toe region and linear elastic region. This project has promising research potential across various disciplines: vascular engineering, nerve regeneration, and ligament and tendon tissue engineering. PMID:27141530

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

PubMed

Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly. Copyright © 2018 the authors 0270-6474/18/384610-11$15.00/0.

Neuroplasticity in the auditory system.

PubMed

Gil-Loyzaga, P

2005-01-01

An increasing interest on neuroplasticity and nerve regeneration within the auditory receptor and pathway has developed in recent years. The receptor and the auditory pathway are controlled by highly complex circuits that appear during embryonic development. During this early maturation process of the auditory sensory elements, we observe the development of two types of nerve fibers: permanent fibers that will remain to reach full-term maturity and other transient fibers that will ultimately disappear. Both stable and transitory fibers however, as well as developing sensory cells, express, and probably release, their respective neuro-transmitters that could be involved in neuroplasticity. Cell culture experiments have added significant information; the in vitro administration of glutamate or GABA to isolated spiral ganglion neurons clearly modified neural development. Neuroplasticity has been also found in the adult. Nerve regeneration and neuroplasticity have been demonstrated in the adult auditory receptors as well as throughout the auditory pathway. Neuroplasticity studies could prove interesting in the elaboration of current or future therapy strategies (e.g.: cochlear implants or stem cells), but also to really understand the pathogenesis of auditory or language diseases (e.g.: deafness, tinnitus, dyslexia, etc.).

Important role of collective cell migration and nerve fiber density in the development of deep nodular endometriosis.

PubMed

Orellana, Renan; García-Solares, Javier; Donnez, Jacques; van Kerk, Olivier; Dolmans, Marie-Madeleine; Donnez, Olivier

2017-04-01

To evaluate deep nodular endometriotic lesions induced in baboons over 12 months and analyze collective cell migration and nerve fiber density. Morphologic and immunohistochemical analysis of endometriotic lesions induced in baboons over the course of 1 year. Academic research unit. Three female baboons (Papio anubis). Recovery of induced deep nodular endometriotic nodules from baboons. Evaluation of the morphology of glands by analysis of the center of lesions and the invasion front; immunohistochemical staining with Ki67, E-cadherin, and β-catenin for investigation of mitotic activity and cell-cell junctions, and with protein gene product 9.5 and nerve growth factor (NGF) for study of nerve fiber density (NFD). All (100%) of the lesions were invasive 1 year after induction, compared with 42.29% after 6 months. Glands from the invasion front showed significantly reduced thickness but significantly higher mitotic activity. E-Cadherin and β-catenin expression were similar between the center and front. NFD was significantly higher in lesions induced after 1 year than after 6 months, and NGF expression was significantly lower in 1-year lesions than in 6-month lesions. Nodular endometriotic lesions induced in the baboon model were found to be significantly more invasive and innervated after 12 months than after 6 months. The invasive phenotype was highly expressed in glands at the invasion front, and our study suggests that nerve fibers play a role in the development of lesions as observed in women. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Histological analysis of the aortic nerve in the rat raised in space (Rapid communication on Neurolab Project).

PubMed

Yamasaki, M; Shimizu, T; Miyake, M; Miyamoto, Y; Waki, H; Katsuda, S I; Oishi, H; Nagayama, T; Katahira, K; Wago, H; Okochi, T; Kaneko, M; Matsumoto, S; Mukai, C; Nagaoka, S; Izumi, T; Yanagawa, K; Uemura, M; O-ishi, H

1998-11-01

To study development of the aortic nerve baroreflex under conditions of microgravity, we examined the cross section of the left aortic nerve (LAN), which is the afferent of the baroreflex, in the neonate rats aged 25 days raised in microgravity on the space shuttle Columbia (flight:FLT group) for 16 days. In this paper, we report a part of the result obtained from the data of the myelinated fibers of LAN analyzed with an electron microscope. Two kind of ground control groups were compared to the FLT group; one was asynchronous ground control (AGC) group where the rats were housed in the same cage as that on the shuttle, and the other was vivarium(VIV) group where the rats were housed in a commercial cage. The LANs in each group were extirpated the from rats perfused with a fixative and embedded for histological analysis. We observed the transverse sections of LAN and took pictures of several areas (magnified to x 2K to x 200K). No irregular myelination was found in all fibers of FLT group when they were compared with two control groups. The thickness of myelin of the maximally myelinated fibers were 0.55 +/- 0.17 micrometer in FLT(n=5), 0.45 +/- 0.10 micrometer in AGC(n=5), and O.47 +/- 0.06 micrometer meter in VIV(n=5). There was no significant difference among three groups (unpared t-test). The results suggest that there is no effect of space environment on the myelin formation of each nerve fiber in the aortic nerve.

Computational solution of spike overlapping using data-based subtraction algorithms to resolve synchronous sympathetic nerve discharge

PubMed Central

Su, Chun-Kuei; Chiang, Chia-Hsun; Lee, Chia-Ming; Fan, Yu-Pei; Ho, Chiu-Ming; Shyu, Liang-Yu

2013-01-01

Sympathetic nerves conveying central commands to regulate visceral functions often display activities in synchronous bursts. To understand how individual fibers fire synchronously, we establish “oligofiber recording techniques” to record “several” nerve fiber activities simultaneously, using in vitro splanchnic sympathetic nerve–thoracic spinal cord preparations of neonatal rats as experimental models. While distinct spike potentials were easily recorded from collagenase-dissociated sympathetic fibers, a problem arising from synchronous nerve discharges is a higher incidence of complex waveforms resulted from spike overlapping. Because commercial softwares do not provide an explicit solution for spike overlapping, a series of custom-made LabVIEW programs incorporated with MATLAB scripts was therefore written for spike sorting. Spikes were represented as data points after waveform feature extraction and automatically grouped by k-means clustering followed by principal component analysis (PCA) to verify their waveform homogeneity. For dissimilar waveforms with exceeding Hotelling's T2 distances from the cluster centroids, a unique data-based subtraction algorithm (SA) was used to determine if they were the complex waveforms resulted from superimposing a spike pattern close to the cluster centroid with the other signals that could be observed in original recordings. In comparisons with commercial software, higher accuracy was achieved by analyses using our algorithms for the synthetic data that contained synchronous spiking and complex waveforms. Moreover, both T2-selected and SA-retrieved spikes were combined as unit activities. Quantitative analyses were performed to evaluate if unit activities truly originated from single fibers. We conclude that applications of our programs can help to resolve synchronous sympathetic nerve discharges (SND). PMID:24198782

Method to investigate temporal dynamics of ganglion and other retinal cells in the living human eye

NASA Astrophysics Data System (ADS)

Kurokawa, Kazuhiro; Liu, Zhuolin; Crowell, James; Zhang, Furu; Miller, Donald T.

2018-02-01

The inner retina is critical for visual processing, but much remains unknown about its neural circuitry and vulnerability to disease. A major bottleneck has been our inability to observe the structure and function of the cells composing these retinal layers in the living human eye. Here, we present a noninvasive method to observe both structural and functional information. Adaptive optics optical coherence tomography (AO-OCT) is used to resolve the inner retinal cells in all three dimensions and novel post processing algorithms are applied to extract structure and physiology down to the cellular level. AO-OCT captured the 3D mosaic of individual ganglion cell somas, retinal nerve fiber bundles of micron caliber, and microglial cells, all in exquisite detail. Time correlation analysis of the AO-OCT videos revealed notable temporal differences between the principal layers of the inner retina. The GC layer was more dynamic than the nerve fiber and inner plexiform layers. At the cellular level, we applied a customized correlation method to individual GCL somas, and found a mean time constant of activity of 0.57 s and spread of +/-0.1 s suggesting a range of physiological dynamics even in the same cell type. Extending our method to slower dynamics (from minutes to one year), time-lapse imaging and temporal speckle contrast revealed appendage and soma motion of resting microglial cells at the retinal surface.

Application for the Drosophila ventral nerve cord standard in neuronal circuit reconstruction and in-depth analysis of mutant morphology.

PubMed

Boerner, Jana; Godenschwege, Tanja Angela

2010-09-01

The Drosophila standard brain has been a useful tool that provides information about position and size of different brain structures within a wild-type brain and allows the comparison of imaging data that were collected from individual preparations. Therefore the standard can be used to reveal and visualize differences of brain regions between wild-type and mutant brains and can provide spatial description of single neurons within the nervous system. Recently the standard brain was complemented by the generation of a ventral nerve cord (VNC) standard. Here the authors have registered the major components of a simple neuronal circuit, the Giant Fiber System (GFS), into this standard. The authors show that they can also virtually reconstruct the well-characterized synaptic contact of the Giant Fiber with its motorneuronal target when they register the individual neurons from different preparations into the VNC standard. In addition to the potential application for the standard thorax in neuronal circuit reconstruction, the authors show that it is a useful tool for in-depth analysis of mutant morphology of single neurons. The authors find quantitative and qualitative differences when they compared the Giant Fibers of two different neuroglian alleles, nrg(849) and nrg(G00305), using the averaged wild-type GFS in the standard VNC as a reference.

High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

PubMed

Gizewski, Elke R; Maderwald, Stefan; Linn, Jennifer; Dassinger, Benjamin; Bochmann, Katja; Forsting, Michael; Ladd, Mark E

2014-03-01

The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures.

Extracting the inclination angle of nerve fibers within the human brain with 3D-PLI independent of system properties

NASA Astrophysics Data System (ADS)

Reckfort, Julia; Wiese, Hendrik; Dohmen, Melanie; Grässel, David; Pietrzyk, Uwe; Zilles, Karl; Amunts, Katrin; Axer, Markus

2013-09-01

The neuroimaging technique 3D-polarized light imaging (3D-PLI) has opened up new avenues to study the complex nerve fiber architecture of the human brain at sub-millimeter spatial resolution. This polarimetry technique is applicable to histological sections of postmortem brains utilizing the birefringence of nerve fibers caused by the regular arrangement of lipids and proteins in the myelin sheaths surrounding axons. 3D-PLI provides a three-dimensional description of the anatomical wiring scheme defined by the in-section direction angle and the out-of-section inclination angle. To date, 3D-PLI is the only available method that allows bridging the microscopic and the macroscopic description of the fiber architecture of the human brain. Here we introduce a new approach to retrieve the inclination angle of the fibers independently of the properties of the used polarimeters. This is relevant because the image resolution and the signal transmission inuence the measured birefringent signal (retardation) significantly. The image resolution was determined using the USAF- 1951 testchart applying the Rayleigh criterion. The signal transmission was measured by elliptical polarizers applying the Michelson contrast and histological slices of the optic tract of a postmortem brain. Based on these results, a modified retardation-inclination transfer function was proposed to extract the fiber inclination. The comparison of the actual and the inclination angles calculated with the theoretically proposed and the modified transfer function revealed a significant improvement in the extraction of the fiber inclinations.

Sensitivities of single nerve fibers in the hamster chorda tympani to mixtures of taste stimuli

PubMed Central

1980-01-01

Responses of three groups of neural fibers from the chorda tympani of the hamster to binary mixtures of taste stimuli applied to the tongue were analyzed. The groups displayed different sensitivities to six chemicals at concentrations that had approximately equal effects on the whole nerve. Sucrose-best fibers responded strongly only to sucrose and D-phenylalanine. NaCl-best and HCl-best fibers, responded to four electrolytes: equally to CaCl2 and nearly equally to HCl, but the former responded more to NaCl, and the latter responded more to NH4Cl. The groups of fibers dealt differently with binary mixtures. Sucrose- best fibers responded to a mixture of sucrose and D-phenylalanine as if one of the chemicals had been appropriately increased in concentration, but they responded to a mixture of either one and an electrolyte as if the concentration of sucrose or D-phenylalanine had been reduced. NaCl- best fibers responded to a mixture as if it were a "mixture" of two appropriate concentrations of one chemical, or somewhat less. But, responses of HCl-best fibers to mixtures were greater than that, approaching a sum of responses to components. These results explain effects on the whole nerve, suggest that the sensitivity of a mammalian taste receptor to one chemical can be affected by a second, which may or may not be a stimulus for that receptor, and suggest that some effects of taste mixtures in humans may be the result of peripheral processes. PMID:7190997

Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat.

PubMed

Farahpour, Mohammad Reza; Ghayour, Sina Jangkhahe

2014-12-01

The repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery, plastic and orthopedic surgery. Effect of acetyl-L-carnitine (ALC) loaded chitosan conduit as an in situ delivery system of ALC in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit (CHIT/ALC) filled with 10 μL ALC (100 ng/mL). In control group (CHIT), the conduit was filled with the same volume of the phosphate buffered solution. The regenerated fibers were studied 4, 8, 12 and 16 weeks after surgery. The functional and electrophysiological studies confirmed faster recovery of the regenerated axons in ALC treated than control group (P < 0.05). The mean ratios of gastrocnemius muscles weight were measured. There was statistically significant difference between the muscle weight ratios of CHIT/ALC and CHIT groups (P<0.05). Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers in CHIT/ALC were significantly higher than in control group. In immuohistochemistry, the location of reactions to S-100 in CHIT/ALC was clearly more positive than CHIT group. ALC when loaded in a chitosan conduit resulted in improvement of functional recovery and quantitative morphometric indices of sciatic nerve. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

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

PubMed

Vucic, Steve; Kiernan, Matthew C

2008-03-01

Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

Fibrolipomatous hamartoma: pathognomonic on MR imaging.

PubMed

Marom, E M; Helms, C A

1999-05-01

To assess the MR imaging characteristics, presenting symptoms, age and nerve distribution of fibrolipomatous hamartoma. A computer search was performed of the term fibrolipomatous hamartoma through the musculoskeletal section MR imaging results at our institution from June 7, 1996 to January 21, 1998 followed by a search of the terms lipomatous hamartoma, median nerve, surrounding fat, increased fatty signal, coaxial, and neuroma. MR images and medical files were retrospectively reviewed by two experienced musculoskeletal radiologists for imaging characteristics, nerve and age distribution as well as for history of trauma. In addition three consultation cases from outside institutions were added for determination of image characteristics. Ten fibrolipomatous hamartomas were identified: eight in the median nerve, one in the ulnar nerve and one in the sciatic nerve. Mean age was 32.3 years (range 4-75 years, SD 21 years). Imaging characteristics were serpiginous low-intensity structures representing thickened nerve fascicles, surrounded by evenly distributed fat, high signal intensity on T1-weighted sequences and low signal intensity on T2-weighted sequences. The amount of fat varied; however, distribution in eight cases (80%) was predominantly between nerve fibers rather than surrounding them peripherally. All had a coaxial-cable-like appearance on axial planes and a spaghetti-like appearance on coronal planes that was not seen in any other type of median nerve abnormality imaged during the study period. The MR imaging characteristics of fibrolipomatous hamartoma are pathognomonic, obviating the need for biopsy for diagnosis.

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

NASA Astrophysics Data System (ADS)

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

2015-03-01

Over 30% of combat injuries involve peripheral nerve injury compared to only 3% in civilian trauma. In fact, nerve dysfunction is the second leading cause of long-term disability in injured service members and is present in 37% of upper limb injuries with disability. Identification and assessment of non-penetrating nerve injury in trauma patients could improve outcome and aid in therapeutic monitoring. We report the use of Raman spectroscopy as a noninvasive, non-destructive method for detection of nerve degeneration in intact nerves due to non-penetrating trauma. Nerve trauma was induced via compression and ischemia/reperfusion injury using a combat relevant swine tourniquet model (>3 hours ischemia). Control animals did not undergo compression/ischemia. Seven days post-operatively, sciatic and femoral nerves were harvested and fixed in formalin. Raman spectra of intact, peripheral nerves were collected using a fiber-optic probe with 3 mm diameter spot size and 785 nm excitation. Data was preprocessed, including fluorescence background subtraction, and Raman spectroscopic metrics were determined using custom peak fitting MATLAB scripts. The abilities of bivariate and multivariate analysis methods to predict tissue state based on Raman spectroscopic metrics are compared. Injured nerves exhibited changes in Raman metrics indicative of 45% decreased myelin content and structural damage (p<<0.01). Axonal and myelin degeneration, cell death and digestion, and inflammation of nerve tissue samples were confirmed via histology. This study demonstrates the non-invasive ability of Raman spectroscopy to detect nerve degeneration associated with non-penetrating injury, relevant to neurapraxic and axonotmetic injuries; future experiments will further explore the clinical utility of Raman spectroscopy to recognize neural injury.

Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration.

PubMed

Malania, Maka; Konrad, Julia; Jägle, Herbert; Werner, John S; Greenlee, Mark W

2017-06-01

Macular degeneration (MD) affects the central retina and leads to gradual loss of foveal vision. Although, photoreceptors are primarily affected in MD, the retinal nerve fiber layer (RNFL) and central visual pathways may also be altered subsequent to photoreceptor degeneration. Here we investigate whether retinal damage caused by MD alters microstructural properties of visual pathways using diffusion-weighted magnetic resonance imaging. Six MD patients and six healthy control subjects participated in the study. Retinal images were obtained by spectral-domain optical coherence tomography (SD-OCT). Diffusion tensor images (DTI) and high-resolution T1-weighted structural images were collected for each subject. We used diffusion-based tensor modeling and probabilistic fiber tractography to identify the optic tract (OT) and optic radiations (OR), as well as nonvisual pathways (corticospinal tract and anterior fibers of corpus callosum). Fractional anisotropy (FA) and axial and radial diffusivity values (AD, RD) were calculated along the nonvisual and visual pathways. Measurement of RNFL thickness reveals that the temporal circumpapillary retinal nerve fiber layer was significantly thinner in eyes with macular degeneration than normal. While we did not find significant differences in diffusion properties in nonvisual pathways, patients showed significant changes in diffusion scalars (FA, RD, and AD) both in OT and OR. The results indicate that the RNFL and the white matter of the visual pathways are significantly altered in MD patients. Damage to the photoreceptors in MD leads to atrophy of the ganglion cell axons and to corresponding changes in microstructural properties of central visual pathways.

Dipole source encoding and tracking by the goldfish auditory system.

PubMed

Coombs, Sheryl; Fay, Richard R; Elepfandt, Andreas

2010-10-15

In goldfish and other otophysans, the Weberian ossicles mechanically link the saccule of the inner ear to the anterior swimbladder chamber (ASB). These structures are correlated with enhanced sound-pressure sensitivity and greater sensitivity at high frequencies (600-2000 Hz). However, surprisingly little is known about the potential impact of the ASB on other otolithic organs and about how auditory responses are modulated by discrete sources that change their location or orientation with respect to the ASB. In this study, saccular and lagenar nerve fiber responses and conditioned behaviors of goldfish were measured to a small, low-frequency (50 Hz) vibrating sphere (dipole) source as a function of its location along the body and its orientation with respect to the ASB. Conditioned behaviors and saccular nerve fiber activity exhibited response characteristics nearly identical to those measured from a hydrophone in the same relative position as the ASB. By contrast, response patterns from lagena fibers could not be predicted by pressure inputs to the ASB. Deflation of the ASB abolished the characteristic spatial response pattern of saccular but not lagena fibers. These results show that: (1) the lagena is not driven by ASB-mediated pressure inputs to the ear; (2) the ASB-saccule pathway dominates behavioral responsiveness, operating effectively at frequencies as low as 50 Hz; and (3) behavioral and neural (saccular) responses are strongly modulated by the position and orientation of the dipole with respect to the ASB.

Spike rate of multi-unit muscle sympathetic nerve fibers following catheter-based renal nerve ablation

PubMed Central

Tank, Jens; Heusser, Karsten; Brinkmann, Julia; Schmidt, Bernhard M.; Menne, Jan; Bauersachs, Johann; Haller, Hermann; Diedrich, André; Jordan, Jens

2016-01-01

Patients with treatment-resistant arterial hypertension exhibited profound reductions in single sympathetic vasoconstrictor fiber firing rates following renal nerve ablation. In contrast, integrated multi-unit muscle sympathetic nerve activity (MSNA) changed little or not at all. We hypothesized that conventional MSNA analysis may have missed single fiber discharges, thus, obscuring sympathetic inhibition following renal denervation. We studied patients with difficult to control arterial hypertension (age 45–74 years) before, 6 (n=11), and 12 months (n=8) following renal nerve ablation. Electrocardiogram, respiration, brachial, and finger arterial blood pressure (BP), as well as the MSNA raw MSNA signal were analyzed. We detected MSNA action potential spikes using 2 stage kurtosis wavelet denoising techniques to assess mean, median, and maximum spike rates for each beat-to-beat interval. Supine heart rate and systolic BP did not change at 6 (ΔHR: −2±3 bpm; ΔSBP: 2±9 mmHg) or at 12 months (ΔHR: −1±3 mmHg, ΔSBP: −1±9 mmHg) after renal nerve ablation. Mean burst frequency and mean spike frequency at baseline were 34±3 bursts per minute and 8±1 spikes per sec. Both measurements did not change at 6 months (−1.4±3.6 bursts/minute; −0.6±1.4 spikes per sec) or at 12 months (−2.5±4.0 bursts/minute; −2.0±1.6 spikes per sec) following renal nerve ablation. After renal nerve ablation, BP decreased in 3 out of 11 patients. BP and MSNA spike frequency changes were not correlated (slope=−0.06; p=0.369). Spike rate analysis of multi-unit MSNA neurograms further suggests that profound sympathetic inhibition is not a consistent finding following renal nerve ablation. PMID:26324745

[The eye and nutrition].

PubMed

Amemiya, T

1999-12-01

To examine the effect of vitamins and trace elements on ocular tissue. Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B12, C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyser, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens. Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus. Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B12 deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B12 was found to be related to the circadian rhythm in the retina. Deficiencies of Zn, Cu, Mn, and vitamins A, B12, and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers. In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer. Zn seemed to be necessary for corneal epithelial cell wound healing. Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance. Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B12, C, and E are necessary for maintenance of cellular structure and metabolism.

The eye and nutrition

PubMed

Amemiya

2000-05-01

Purpose: To examine the effect of vitamins and trace elements on ocular tissue.Materials and Methods: Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B(12), C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyzer, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens.Results: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus.Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B(12) deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B(12) was found to be related to the circadian rhythm in the retina.Deficiencies of Zn, Cu, Mn, and vitamins A, B(12), and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers.In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer.Zn seemed to be necessary for corneal epithelial cell wound healing.Discussion: Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance.Conclusion: Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B(12), C, and E are necessary for maintenance of cellular structure and metabolism.

Development of active and sensitive material systems based on composites

NASA Astrophysics Data System (ADS)

Asanuma, Hiroshi

2002-07-01

This paper describes new concepts proposed by the author to realize active and sensitive structural material systems. Two examples of multifunctional composites were fabricated and evaluated in this study as follows: (1) An active laminate of aluminum plate (works as muscle), epoxy film (as insulator), unidirectional CFRP prepreg (as bone and blood vessel) and copper foil electrode (to apply voltage on CFRP) was made with an embedded optical fiber multiply fractured in the CFRP layer (works as nerve), of which curvature change could be effectively monitored with the fractured optical fiber. (2) A stainless steel fiber/aluminum active composite with embedded Ti oxide/Ti composite fiber was fabricated. The Ti oxide/Ti fiber could work as a sensor for temperature by removing a part of the oxide before embedment to make a metallic contact between the embedded titanium fiber and aluminum matrix to be able to generate thermal electromotive force, and also could work as a sensor for strain and as a heater for actuation. In the both cases, the outputs from their embedded sensors can be used to control their actuations.

Central projections of the nervus terminalis and the nervus praeopticus in the lungfish brain revealed by nitric oxide synthase.

PubMed

Schober, A; Meyer, D L; Von Bartheld, C S

1994-11-01

Lungfishes possess two cranial nerves that are associated with the olfactory system: the nervus terminalis enters the telencephalon with the olfactory nerve, and the nervus praeopticus enters the diencephalon at the level of the optic nerve. We investigated the central projections of the nervus terminalis and the nervus praeopticus in the Australian lungfish (Neoceratodus forsteri) and in the African lungfish (Protopterus dolloi) by NADPH-diaphorase histochemistry (nitric oxide synthase; NOS) and compared them with the projections of the nervus terminalis of the frog (Xenopus laevis). In Neoceratodus, NOS-positive fascicles of the nervus terminalis divide and project with a ventral component through the septum and with a dorsal component through the pallium; fibers of both trajectories extend caudally beyond the anterior commissure and join the lateral forebrain bundle. In the nervus praeopticus, about 300 fibers contain NOS; they innervate the preoptic nucleus and continue their course through the diencephalon; many fibers cross in the commissure of the posterior tuberculum. In Protopterus, ganglion cells of the nervus terminalis and of the nervus praeopticus contain NOS. NOS-positive fibers of the nervus terminalis project through the septal region but not through the pallium. Several major fascicles cross in the rostral part of the anterior commissure, where they are joined by a small number of NOS-containing fibers of the nervus praeopticus. Both nerves innervate the preoptic nucleus. The number and pathways of the fascicles of the nervus terminalis are not always symmetric between the two sides. The nervus terminalis fascicles remain in a ventral position, whereas the nervus praeopticus gives rise to the more dorsal fascicles. Many fibers of the two nerves extend throughout the diencephalon and cross in the commissure of the posterior tuberculum. These findings demonstrate many similarities but also significant differences between the contributions of the nervus terminalis and the nervus praeopticus to forebrain projections in the two lungfishes. They support the view that the nervus praeopticus is part of a nervus terminalis system comparable to that in frogs and other nonmammalian vertebrates.

Axonal transport of class II and III beta-tubulin: evidence that the slow component wave represents the movement of only a small fraction of the tubulin in mature motor axons

PubMed Central

1992-01-01

Pulse-labeling studies demonstrate that tubulin synthesized in the neuron cell body (soma) moves somatofugally within the axon (at a rate of several millimeters per day) as a well-defined wave corresponding to the slow component of axonal transport. A major goal of the present study was to determine what proportion of the tubulin in mature motor axons is transported in this wave. Lumbar motor neurons in 9-wk-old rats were labeled by injecting [35S]methionine into the spinal cord 2 wk after motor axons were injured (axotomized) by crushing the sciatic nerve. Immunoprecipitation with mAbs which recognize either class II or III beta-tubulin were used to analyze the distributions of radioactivity in these isotypes in intact and axotomized motor fibers 5 d after labeling. We found that both isotypes were associated with the slow component wave, and that the leading edge of this wave was enriched in the class III isotype. Axotomy resulted in significant increases in the labeling and transport rates of both isotypes. Immunohistochemical examination of peripheral nerve fibers demonstrated that nearly all of the class II and III beta-tubulin in nerve fibers is located within axons. Although the amounts of radioactivity per millimeter of nerve in class II and III beta-tubulin were significantly greater in axotomized than in control nerves (with increases of +160% and +58%, respectively), immunoassay revealed no differences in the amounts of these isotypes in axotomized and control motor fibers. We consider several explanations for this paradox; these include the possibility that the total tubulin content is relatively insensitive to changes in the amount of tubulin transported in the slow component wave because this wave represents the movement of only a small fraction of the tubulin in these motor fibers. PMID:1383234

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

PubMed

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, <5 microm for each instrument). In the control group, there also was no significant change in GDx 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 < or = 0.001). LASIK does not seem to change RNFL thickness. Reduction in GDx 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.

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.

PubMed

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 < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central 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.

Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve.

PubMed

Sarabia-Estrada, Rachel; Bañuelos-Pineda, Jacinto; Osuna Carrasco, Laura P; Jiménez-Vallejo, Salvador; Jiménez-Estrada, Ismael; Rivas-Celis, Efrain; Dueñas-Jiménez, Judith M; Dueñas-Jiménez, Sergio H

2015-07-01

Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesterone-impregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats. After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electro-myographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection. At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes. Some gastrocnemius efferent fibers were partially repaired 90 days after nerve resection. The better outcome in knee angle displacement may be partially attributable to the aberrant neuromuscular synaptic effects, since nerve conduction in the gastrocnemius muscle could be blocked in the progesterone-impregnated chitosan tubes. In addition, in the region of the gap produced by the nerve resection, the number of axons and amount of myelination were reduced in the sciatic nerve implanted with chitosan, progesterone-loaded chitosan, and silicone tubes. At 180 days after sciatic nerve sectioning, the knee kinematic function recovered to a level observed in control rats of a similar age. In rats with progesterone-loaded chitosan tubes, stimulation of the proximal and intratubular sciatic nerve segments produced an electromyographic response. The axon morphology of the proximal and intratubular segments of the sciatic nerve resembled that of the contralateral nontransected nerve. Progesterone-impregnated chitosan tubes produced aberrant innervation of the gastrocnemius muscle, which allowed partial recovery of gait locomotion and could be adequate for reinnervating synergistic denervated muscles while a parent innervation is reestablished. Hindlimb kinematic parameters differed between younger (those at 90 days) and older (those at 180 days) rats.

Renal artery nerve distribution and density in the porcine model: biologic implications for the development of radiofrequency ablation therapies.

PubMed

Tellez, Armando; Rousselle, Serge; Palmieri, Taylor; Rate, William R; Wicks, Joan; Degrange, Ashley; Hyon, Chelsea M; Gongora, Carlos A; Hart, Randy; Grundy, Will; Kaluza, Greg L; Granada, Juan F

2013-12-01

Catheter-based renal artery denervation has demonstrated to be effective in decreasing blood pressure among patients with refractory hypertension. The anatomic distribution of renal artery nerves may influence the safety and efficacy profile of this procedure. We aimed to describe the anatomic distribution and density of periarterial renal nerves in the porcine model. Thirty arterial renal sections were included in the analysis by harvesting a tissue block containing the renal arteries and perirenal tissue from each animal. Each artery was divided into 3 segments (proximal, mid, and distal) and assessed for total number, size, and depth of the nerves according to the location. Nerve counts were greatest proximally (45.62% of the total nerves) and decreased gradually distally (mid, 24.58%; distal, 29.79%). The distribution in nerve size was similar across all 3 sections (∼40% of the nerves, 50-100 μm; ∼30%, 0-50 μm; ∼20%, 100-200 μm; and ∼10%, 200-500 μm). In the arterial segments ∼45% of the nerves were located within 2 mm from the arterial wall whereas ∼52% of all nerves were located within 2.5 mm from the arterial wall. Sympathetic efferent fibers outnumbered sensory afferent fibers overwhelmingly, intermixed within the nerve bundle. In the porcine model, renal artery nerves are seen more frequently in the proximal segment of the artery. Nerve size distribution appears to be homogeneous throughout the artery length. Nerve bundles progress closer to the arterial wall in the distal segments of the artery. This anatomic distribution may have implications for the future development of renal denervation therapies. Crown Copyright © 2013. Published by Mosby, Inc. All rights reserved.

Evidence that hidden hearing loss underlies amplitude modulation encoding deficits in individuals with and without tinnitus.

PubMed

Paul, Brandon T; Bruce, Ian C; Roberts, Larry E

2017-02-01

Damage to auditory nerve fibers that expresses with suprathreshold sounds but is hidden from the audiogram has been proposed to underlie deficits in temporal coding ability observed among individuals with otherwise normal hearing, and to be present in individuals experiencing chronic tinnitus with clinically normal audiograms. We tested whether these individuals may have hidden synaptic losses on auditory nerve fibers with low spontaneous rates of firing (low-SR fibers) that are important for coding suprathreshold sounds in noise while high-SR fibers determining threshold responses in quiet remain relatively unaffected. Tinnitus and control subjects were required to detect the presence of amplitude modulation (AM) in a 5 kHz, suprathreshold tone (a frequency in the tinnitus frequency region of the tinnitus subjects, whose audiometric thresholds were normal to 12 kHz). The AM tone was embedded within background noise intended to degrade the contribution of high-SR fibers, such that AM coding was preferentially reliant on low-SR fibers. We also recorded by electroencephalography the "envelope following response" (EFR, generated in the auditory midbrain) to a 5 kHz, 85 Hz AM tone presented in the same background noise, and also in quiet (both low-SR and high-SR fibers contributing to AM coding in the latter condition). Control subjects with EFRs that were comparatively resistant to the addition of background noise had better AM detection thresholds than controls whose EFRs were more affected by noise. Simulated auditory nerve responses to our stimulus conditions using a well-established peripheral model suggested that low-SR fibers were better preserved in the former cases. Tinnitus subjects had worse AM detection thresholds and reduced EFRs overall compared to controls. Simulated auditory nerve responses found that in addition to severe low-SR fiber loss, a degree of high-SR fiber loss that would not be expected to affect audiometric thresholds was needed to explain the results in tinnitus subjects. The results indicate that hidden hearing loss could be sufficient to account for impaired temporal coding in individuals with normal audiograms as well as for cases of tinnitus without audiometric hearing loss. Copyright © 2016 Elsevier B.V. All rights reserved.

Long-term consequences of topical dexamethasone treatment during acute corneal HSV-1 infection on the immune system

PubMed Central

Chucair-Elliott, Ana J.; Carr, Meghan M.; Carr, Daniel J. J.

2017-01-01

Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis (NTK). NTK is characterized by decreased corneal sensation from damage to the corneal sensory fibers. We have reported on the regression of corneal nerves and their function during acute HSV-1 infection. That nerve loss is followed by an aberrant process of nerve regeneration during the latent phase of infection that lacks functional recovery. We recently showed the elicited immune response in the infected cornea, and not viral replication itself, is part of the mechanism responsible for the nerve degeneration process after infection. Specifically, we showed infected corneas topically treated with dexamethasone (DEX) significantly retained both structure and sensitivity of the corneal nerve network in comparison to mice treated with control eye drops, consistent with decreased levels of proinflammatory cytokines and reduced influx of macrophages and CD8+ T cells into the cornea. This study was undertaken to analyze the long-term effect of such a localized, immunosuppressive paradigm (DEX drops on the cornea surface during the first 8 d of HSV-1 infection) on the immune system and on corneal pathology. We found the profound immunosuppressive effect of DEX on lymphoid tissue was sustained in surviving mice for up to 30 d postinfection (p.i.). DEX treatment had prolonged effects, preserving corneal innervation and its function and blunting neovascularization, as analyzed at 30 d p.i. Our data support previously reported observations of an association between the persistent presence of inflammatory components in the latently infected cornea and structural and functional nerve defects in NTK. PMID:28115476

A novel histochemical method of simultaneous detection by a single- or double-immunofluorescence and Bielschowsky's silver staining in teased rat sciatic nerves.

PubMed

Segura-Anaya, Edith; Flores-Miranda, Rommel; Martínez-Gómez, Alejandro; Dent, Myrna A R

2018-07-01

The Golgi silver method has been widely used in neuroscience for the study of normal and pathological morphology of neurons. The method has been steadily improved and Bielschowsky's silver staining method (BSSM) is widely used in various pathological conditions, like Alzheimer's disease. In this work, teased sciatic nerves were silver impregnated using BSSM. We also developed simultaneous staining by silver impregnation and single- or double-immunofluorescence of the same section in teased nerve preparations. We immunostained against non-myelinating Schwann cells and different myelinating Schwann cell domains. BSSM teased nerves show a strong staining of axons (black) and a gold-brown staining of myelinating and non-myelinating Schwann cells. We were also able to stain by immunofluorescence these BSSM teased nerves with specific molecular markers against non-myelinating Schwann cells, also against non-compact myelin such as the Schmidt-Lanterman incisures or paranodal regions and compact myelin, but not axons. In peripheral nerves, several silver impregnation methods have been used to stain nerves in paraffin sections, but not in teased nerves to enable the assessment of isolated nerve fibers. In conclusion, BSSM gives accurate information of nerve morphology and combining the procedure with immunofluorescence it would be very useful to study the molecular nerve domain organization of the nerve fibers, and to study the molecular pathology of axon degeneration, or myelin disorders, or of any peripheral neuropathy, also to study demyelination diseases in the central nervous system. Copyright © 2018. Published by Elsevier B.V.

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

PubMed

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

NASA Technical Reports Server (NTRS)

Gupta, R. C.; Misulis, K. E.; Dettbarn, W. D.

1984-01-01

Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

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

PubMed

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.

Novel Immunohistochemical Techniques Using Discrete Signal Amplification Systems for Human Cutaneous Peripheral Nerve Fiber Imaging

PubMed Central

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

2011-01-01

Confocal imaging uses immunohistochemical binding of specific antibodies to visualize tissues, but technical obstacles limit more widespread use of this technique in the imaging of peripheral nerve tissue. These obstacles include same-species antibody cross-reactivity and weak fluorescent signals of individual and co-localized antigens. The aims of this study were to develop new immunohistochemical techniques for imaging of peripheral nerve fibers. Three-millimeter punch skin biopsies of healthy individuals were fixed, frozen, and cut into 50-µm sections. Tissues were stained with a variety of antibody combinations with two signal amplification systems, streptavidin-biotin-fluorochrome (sABC) and tyramide-horseradish peroxidase-fluorochrome (TSA), used simultaneously to augment immunohistochemical signals. The combination of the TSA and sABC amplification systems provided the first successful co-localization of sympathetic adrenergic and sympathetic cholinergic nerve fibers in cutaneous human sweat glands and vasomotor and pilomotor systems. Primary antibodies from the same species were amplified individually without cross-reactivity or elevated background interference. The confocal fluorescent signal-to-noise ratio increased, and image clarity improved. These modifications to signal amplification systems have the potential for widespread use in the study of human neural tissues. PMID:21411809

Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

PubMed Central

Mulder, Jan; Hökfelt, Tomas; Knuepfer, Mark M.

2013-01-01

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation. PMID:23408032

Granulocyte colony-stimulating factor (G-CSF) positive effects on muscle fiber degeneration and gait recovery after nerve lesion in MDX mice

PubMed Central

Simões, Gustavo F; Benitez, Suzana U; Oliveira, Alexandre L R

2014-01-01

Background G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. Aims The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. Methods Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75NTR and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. Results Both groups treated with G-CSF showed increased p75NTR and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. Conclusions The reduction in p75NTR and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF. PMID:25328849

Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus.

PubMed

Sedlacek, Miloslav; Brenowitz, Stephan D

2014-01-01

Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

Electrophysiological abnormalities associated with extensive myelinated retinal nerve fibers.

PubMed

Tay, Su Ann; Sanjay, Srinivasan

2012-07-01

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

Natural Occurring Silks and Their Analogues as Materials for Nerve Conduits.

PubMed

Radtke, Christine

2016-10-20

Spider silk and its synthetic derivatives have a light weight in combination with good strength and elasticity. Their high cytocompatibility and low immunogenicity make them well suited for biomaterial products such as nerve conduits. Silk proteins slowly degrade enzymatically in vivo, thus allowing for an initial therapeutic effect such as in nerve scaffolding to facilitate endogenous repair processes, and then are removed. Silks are biopolymers naturally produced by many species of arthropods including spiders, caterpillars and mites. The silk fibers are secreted by the labial gland of the larvae of some orders of Holometabola (insects with pupa) or the spinnerets of spiders. The majority of studies using silks for biomedical applications use materials from silkworms or spiders, mostly of the genus Nephila clavipes . Silk is one of the most promising biomaterials with effects not only in nerve regeneration, but in a number of regenerative applications. The development of silks for human biomedical applications is of high scientific and clinical interest. Biomaterials in use for biomedical applications have to meet a number of requirements such as biocompatibility and elicitation of no more than a minor inflammatory response, biodegradability in a reasonable time and specific structural properties. Here we present the current status in the field of silk-based conduit development for nerve repair and discuss current advances with regard to potential clinical transfer of an implantable nerve conduit for enhancement of nerve regeneration.

Protective effect of fenspiride on the bronchi in rats with chronic obstructive pulmonary disease.

PubMed

Kuzubova, N A; Lebedeva, E S; Fedin, A N; Dvorakovskaya, I V; Titova, O N

2013-06-01

We studied the effect of a non-steroidal anti-inflammatory drug fenspiride on contractive activity of bronchial smooth muscles on the model of chronic obstructive pulmonary disease of rats induced by 60-day exposure to nitrogen dioxide. The administration of fenspiride during the acute stage of the disease (day 15) abolished the constricting effect of the pollutant on the bronchial smooth muscles. Dilatation effect of fenspiride in a low dose (0.15 mg/kg) was mediated by its interaction with nerve endings of bronchial capsaicin-sensitive nerve C-fibers. The interaction of drug with receptors of C-fibers prevented neurogenic inflammation, which was confirmed by the absence of structural changes in the lungs typical of this pathology. The broncholytic effect of fenspiride in a high dose (15 mg/kg) was mediated by not only afferent pathways, but also its direct relaxing action on smooth muscle cells. The observed anti-inflammatory and bronchodilatation effect of fenspiride in very low doses can be used for prevention of chronic obstructive pulmonary disease in risk-group patients contacting with aggressive environmental factors.

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator.

PubMed

Ibañez Rodriguez, María P; Noctor, Stephen C; Muñoz, Estela M

2016-01-01

The adult pineal gland is composed of pinealocytes, astrocytes, microglia, and other interstitial cells that have been described in detail. However, factors that contribute to pineal development have not been fully elucidated, nor have pineal cell lineages been well characterized. We applied systematic double, triple and quadruple labeling of cell-specific markers on prenatal, postnatal and mature rat pineal gland tissue combined with confocal microscopy to provide a comprehensive view of the cellular dynamics and cell lineages that contribute to pineal gland development. The pineal gland begins as an evagination of neuroepithelium in the roof of the third ventricle. The pineal primordium initially consists of radially aligned Pax6+ precursor cells that express vimentin and divide at the ventricular lumen. After the tubular neuroepithelium fuses, the distribution of Pax6+ cells transitions to include rosette-like structures and later, dispersed cells. In the developing gland all dividing cells express Pax6, indicating that Pax6+ precursor cells generate pinealocytes and some interstitial cells. The density of Pax6+ cells decreases across pineal development as a result of cellular differentiation and microglial phagocytosis, but Pax6+ cells remain in the adult gland as a distinct population. Microglial colonization begins after pineal recess formation. Microglial phagocytosis of Pax6+ cells is not common at early stages but increases as microglia colonize the gland. In the postnatal gland microglia affiliate with Tuj1+ nerve fibers, IB4+ blood vessels, and Pax6+ cells. We demonstrate that microglia engulf Pax6+ cells, nerve fibers, and blood vessel-related elements, but not pinealocytes. We conclude that microglia play a role in pineal gland formation and homeostasis by regulating the precursor cell population, remodeling blood vessels and pruning sympathetic nerve fibers.

Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator

PubMed Central

Ibañez Rodriguez, María P.

2016-01-01

The adult pineal gland is composed of pinealocytes, astrocytes, microglia, and other interstitial cells that have been described in detail. However, factors that contribute to pineal development have not been fully elucidated, nor have pineal cell lineages been well characterized. We applied systematic double, triple and quadruple labeling of cell-specific markers on prenatal, postnatal and mature rat pineal gland tissue combined with confocal microscopy to provide a comprehensive view of the cellular dynamics and cell lineages that contribute to pineal gland development. The pineal gland begins as an evagination of neuroepithelium in the roof of the third ventricle. The pineal primordium initially consists of radially aligned Pax6+ precursor cells that express vimentin and divide at the ventricular lumen. After the tubular neuroepithelium fuses, the distribution of Pax6+ cells transitions to include rosette-like structures and later, dispersed cells. In the developing gland all dividing cells express Pax6, indicating that Pax6+ precursor cells generate pinealocytes and some interstitial cells. The density of Pax6+ cells decreases across pineal development as a result of cellular differentiation and microglial phagocytosis, but Pax6+ cells remain in the adult gland as a distinct population. Microglial colonization begins after pineal recess formation. Microglial phagocytosis of Pax6+ cells is not common at early stages but increases as microglia colonize the gland. In the postnatal gland microglia affiliate with Tuj1+ nerve fibers, IB4+ blood vessels, and Pax6+ cells. We demonstrate that microglia engulf Pax6+ cells, nerve fibers, and blood vessel-related elements, but not pinealocytes. We conclude that microglia play a role in pineal gland formation and homeostasis by regulating the precursor cell population, remodeling blood vessels and pruning sympathetic nerve fibers. PMID:27861587

Foveomacular schisis in juvenile X-linked retinoschisis: an optical coherence tomography study.

PubMed

Yu, Jia; Ni, Yingqin; Keane, Pearse A; Jiang, Chunhui; Wang, Wenji; Xu, Gezhi

2010-06-01

To explore the structural features of juvenile X-linked retinoschisis using spectral-domain optical coherence tomography (OCT). Retrospective, observational cross-sectional study. Eighteen male patients (34 eyes) who were diagnosed with juvenile X-linked retinoschisis at the Eye & ENT Hospital of Fudan University over an 18-month period were included. Their OCT images, which were obtained using spectral-domain OCT (Cirrus HD-OCT; Carl Zeiss Meditec), were analyzed. The anatomic location of the schisis cavity in juvenile X-linked retinoschisis was characterized by direct inspection of OCT images. On OCT, the schisis cavity was visible at the fovea in all 34 eyes, and it was associated with increased retinal thickness. Schisis was present at the retinal nerve fiber layer in 4 eyes, at the inner nuclear layer in 29 eyes, and at the outer nuclear layer/outer plexiform layer in 22 eyes. In most cases, widespread foveomacular schisis was detected using OCT; however, in 9 eyes (6 patients), the schisis was confined to the fovea. Schisis of the inner nuclear layer and outer nuclear layer/outer plexiform layer almost always involved the foveal center, but retinal nerve fiber layer schisis was seen only in the parafoveal area. Despite conventional wisdom, in patients with X-linked retinoschisis, the schisis cavity can occur in a number of different layers of the neurosensory retina (retinal nerve fiber layer, inner nuclear layer, and outer nuclear layer/outer plexiform layer). In addition, different forms of schisis may affect different locations in the macula (foveal vs parafoveal), and, in most eyes, the schisis involves the entire foveomacular region. Copyright 2010 Elsevier Inc. All rights reserved.

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... about 10,000 taste buds. The taste buds are linked to the brain by nerve fibers. Food particles are detected by the taste buds, which send nerve ... to the brain. Certain areas of the tongue are more sensitive to certain tastes, like bitter, sour, ...

Distance between intramuscular nerve and artery in the extraocular muscles: a preliminary immunohistochemical study using elderly human cadavers.

PubMed

Kitamura, Kei; Cho, Kwang Ho; Jang, Hyung Suk; Murakami, Gen; Yamamoto, Masahito; Abe, Shin-Ichi

2017-01-01

Extraocular muscles are quite different from skeletal muscles in muscle fiber type and nerve supply; the small motor unit may be the most well known. As the first step to understanding the nerve-artery relationship, in this study we measured the distance from the arteriole (25-50 μm in thickness) to the nerve terminal twigs in extraocular muscles. With the aid of immunohistochemistry for nerves and arteries, we examined the arteriole-nerve distance at 10-15 sites in each of 68 extraocular muscles obtained from ten elderly cadavers. The oblique sections were nearly tangential to the muscle plate and included both global and orbital aspects of the muscle. In all muscles, the nerve twigs usually took a course parallel to muscle fibers, in contrast to most arterioles that crossed muscles. Possibly due to polyinnervation, an intramuscular nerve plexus was evident in four rectus and two oblique muscles. The arteriole-nerve distance usually ranged from 300 to 400 μm. However, individual differences were more than two times greater in each of seven muscles. Moreover, in each muscle the difference between sites sometimes reached 1 mm or more. The distance was generally shorter in the rectus and oblique muscles than in the levator palpebrae muscle, which reached statistical significance (p < 0.05). The differences in arteriole-nerve distances between sites within each muscle, between muscles, and between individuals might lead to an individual biological rhythm of fatigue in oculomotor performance.

Some posterior branches of extralaryngeal recurrent laryngeal nerves have motor fibers.

PubMed

Cho, Ilyoung; Jo, Min-Gyu; Choi, Sung-Won; Jang, Jeon Yeob; Wang, Soo-Geun; Cha, Wonjae

2017-11-01

Anatomical variations of the recurrent laryngeal nerve (RLN), such as extralaryngeal branching, are a well-known risk factor for RLN injury during thyroid surgery. This study aimed to analyze the surgical anatomy and to investigate the existence of posterior branch motor fibers of extralaryngeal RLNs. Prospective consecutive observational study. This was a prospective cohort study of 366 patients between January 2014 and February 2016. Operative data included the type of operation, incidence of nerve bifurcation, the distances among anatomical landmarks. The motor fibers were evaluated using neurostimulation with laryngeal palpation. A total of 667 RLNs at risk were analyzed in this study, and of these 103 (14.5%) nerves were bifurcated or trifurcated before the laryngeal entry point (LEP). More extralaryngeal branched RLNs were observed on the right side than on the left (17.5% vs. 13.3%, P = .294). The mean distance of the LEP point of division was longer on the left side (16.2 ± 6.7 mm) than on the right (14.7 ± 5.9 mm, P = .132). All branched RLNs had a palpable laryngeal twitch when stimulating anterior branches. When stimulating posterior branches, 28.2%(29/103) of branched RLNs showed palpable laryngeal twitch. Overall incidence of posterior motor branch in total RLNs was 4.3% (29/667). The motor fibers of the RLN are all located in the anterior branch, whereas some posterior branches have motor function. Identification of all of the branches of the RLN may be mandatory to decrease the risk of postoperative nerve injury. 4. Laryngoscope, 127:2678-2685, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years.

PubMed

Garcia-Martin, Elena; Ara, Jose R; Martin, Jesus; Almarcegui, Carmen; Dolz, Isabel; Vilades, Elisa; Gil-Arribas, Laura; Fernandez, Francisco J; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E; Satue, Maria

2017-05-01

To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Observational and longitudinal study. One hundred patients with relapsing-remitting MS and 50 healthy controls. All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

Variations in the course and microanatomical study of the lateral femoral cutaneous nerve and its clinical importance.

PubMed

Ray, Biswabina; D'Souza, A S; Kumar, Brijesh; Marx, Chakravarthy; Ghosh, Buddhadeb; Gupta, Nanda Kishore; Marx, Anitha

2010-11-01

The lateral femoral cutaneous nerve (LFCN), a branch from the lumbar plexus, may come to the clinician's or surgeon's attention. We studied this nerve to determine its location and its relationship with neighboring structures around the anterior superior iliac spine (ASIS) and the inguinal ligament (IL). Additionally, cross-sectional microanatomy of the LFCN at the IL was studied. The LFCN was dissected in 47 lower limbs from formalin-fixed cadavers. The distances from the ASIS to the point where the LFCN crossed the IL and the lateral border of the sartorius were measured. The distance between the ASIS and the point it pierced the deep fascia was also measured. Twelve nerve specimens at the IL were collected for histological sectioning and were stained with hematoxylin and eosin. On examination of the cross-sectional area, the nonfascicular area was wider than the fascicular area because of an increased amount of thick collagen fibers. This study may be of help to clinicians managing meralgia paresthetica and may also assist in defining a safe area for surgical intervention on the anterolateral aspect of the thigh.

Generalized peripheral neuropathy in a dental technician exposed to methyl methacrylate monomer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donaghy, M.; Rushworth, G.; Jacobs, J.M.

1991-07-01

A 58-year-old dental prosthetic technician developed generalized sensorimotor peripheral neuropathy. Neurophysiologic studies showed a generalized sensorimotor neuropathy of axonal degeneration type. Examination of a sural nerve biopsy showed a moderately severe axonal neuropathy with loss of large myelinated fibers and unmyelinated axons. There was evidence of slow ongoing degeneration and considerable fiber regeneration. Electron microscopy showed increased numbers of filaments in a few fibers. These findings show resemblances to the nerve changes caused by another acrylic resin, acrylamide. They suggest that the neuropathy may have been caused by 30 years of occupational cutaneous and inhalational exposure to methyl methacrylate monomermore » since they excluded other recognized causes of neuropathy.« less

PATHOGENESIS OF OPTIC DISC EDEMA IN RAISED INTRACRANIAL PRESSURE

PubMed Central

Hayreh, Sohan Singh

2015-01-01

Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure. PMID:26453995

Pathogenesis of optic disc edema in raised intracranial pressure.

PubMed

Hayreh, Sohan Singh

2016-01-01

Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

PubMed Central

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

2013-01-01

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

Retinal ganglion cell damage in an experimental rodent model of blast-mediated traumatic brain injury.

PubMed

Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H; Harper, Matthew M

2013-05-15

To evaluate retina and optic nerve damage following experimental blast injury. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify.

MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type

PubMed Central

Wu, Hai; Naya, Francisco J.; McKinsey, Timothy A.; Mercer, Brian; Shelton, John M.; Chin, Eva R.; Simard, Alain R.; Michel, Robin N.; Bassel-Duby, Rhonda; Olson, Eric N.; Williams, R. Sanders

2000-01-01

Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myofiber subtypes. Recently, we proposed that the influence of motor nerve activity on skeletal muscle fiber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin-dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium-regulated signaling inputs, specifically calmodulin-dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow fiber-specific enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up-regulates a MEF2-dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myofiber subtypes are established and maintained. PMID:10790363

Key changes in denervated muscles and their impact on regeneration and reinnervation

PubMed Central

Wu, Peng; Chawla, Aditya; Spinner, Robert J.; Yu, Cong; Yaszemski, Michael J.; Windebank, Anthony J.; Wang, Huan

2014-01-01

The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle's residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair. PMID:25422641

Sensory Innervation of the Nonspecialized Connective Tissues in the Low Back of the Rat

PubMed Central

Corey, Sarah M.; Vizzard, Margaret A.; Badger, Gary J.; Langevin, Helene M.

2011-01-01

Chronic musculoskeletal pain, including low back pain, is a worldwide debilitating condition; however, the mechanisms that underlie its development remain poorly understood. Pathological neuroplastic changes in the sensory innervation of connective tissue may contribute to the development of nonspecific chronic low back pain. Progress in understanding such potentially important abnormalities is hampered by limited knowledge of connective tissue's normal sensory innervation. The goal of this study was to evaluate and quantify the sensory nerve fibers terminating within the nonspecialized connective tissues in the low back of the rat. With 3-dimensional reconstructions of thick (30–80 μm) tissue sections we have for the first time conclusively identified sensory nerve fiber terminations within the collagen matrix of connective tissue in the low back. Using dye labeling techniques with Fast Blue, presumptive dorsal root ganglia cells that innervate the low back were identified. Of the Fast Blue-labeled cells, 60–88% also expressed calcitonin gene-related peptide (CGRP) immunoreactivity. Based on the immunolabeling with CGRP and the approximate size of these nerve fibers (≤2 μm) we hypothesize that they are Aδ or C fibers and thus may play a role in the development of chronic pain. PMID:21411968

End-to-side neurorrhaphy with and without perineurium.

PubMed

Viterbo, F; Teixeira, E; Hoshino, K; Padovani, C R

1998-01-01

We compared end-to-side neurorraphy with and without the perineural sheath. Twenty rats were used. The peroneal nerve was sectioned and the distal end was sutured to the lateral face of the tibial nerve. We removed the perineural sheath only on the right side, but not on the left side. The proximal end of the peroneal nerve was curved back approximately at a 100 degrees angle and implanted into the adductor muscle. Six months later, the 14 surviving animals were submitted to electrophysiological tests, sacrificed, and the nerves and muscles were taken for histological exams. On the right side, the muscles that had positive response needed an average of 258.89 mV (+/- 92.31) of electric stimulus and on the left side 298.34 mV (+/- 139.32). The average weight of the tibial cranial muscles of the right side was 0.47 g (0.18) and for the left side 0.45 g (0.15). The distal end of the peroneal nerve showed averages of 310.29 (+/- 191.34) nerve fibers on the right side and 287.71 (+/- 183.60) on the left side. The tibial nerve above the neurorraphy showed averages of 939.46 (+/- 223.51) nerve fibers on the right side and 959.46 (+/- 327.48) on the left side. The tibial nerve below the neurorraphy showed averages of 935.17 (+/- 298.65) nerve fibers on the right side and 755.31 (+/- 323.26) on the left side. The average areas of the right tibial cranial muscles were 0.0162 m2 (+/- 0.008), after 230 magnification, and 0.0152 m2 (0.0064) for the left tibial cranial muscles. The histological features of the tibial cranial muscles, taking normal as 100%, were 78.21 (+/- 20.75) on the right side and 82.14 (+/- 15.89) on the left side. The statistical analysis (Student's t test) did not reveal any difference (p > 0.05) among right and left sides for all variables. The authors concluded that the two neurorraphies (with and without perineurium) did not show any difference regarding morphological and electrophysiological features studied.

Cutaneous sensory and autonomic denervation in CADASIL.

PubMed

Nolano, Maria; Provitera, Vincenzo; Donadio, Vincenzo; Caporaso, Giuseppe; Stancanelli, Annamaria; Califano, Francesca; Pianese, Luigi; Liguori, Rocco; Santoro, Lucio; Ragno, Michele

2016-03-15

To assess the involvement of the peripheral nervous system in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by means of immunofluorescence and confocal analysis of punch skin biopsies. We recruited 14 unrelated patients with CADASIL (M/F = 9/5; age 53.9 ± 10.5 years) and 52 healthy controls (M/F = 31/21; age 53.8 ± 9.8). Patients underwent clinical and neuroradiologic assessment. Three-millimeter punch skin biopsies were taken from the fingertip, the thigh, and the distal leg and processed using indirect immunofluorescence and a panel of primary antibodies to mark vessels and sensory and autonomic nerve fibers. Intraepidermal nerve fibers (IENF), Meissner corpuscles (MC), and sudomotor, vasomotor, and pilomotor nerves were assessed using confocal microscopy. In patients, compared to controls, we found a severe loss of IENF at the distal leg (p < 0.01), at the thigh (p < 0.01), and at the fingertip (p < 0.01) with a non-length-dependent pattern and a loss of MC (p < 0.01). A severe sudomotor, vasomotor, and pilomotor nerve fiber loss was found by semiquantitative evaluation. Along with nerve loss, a severe derangement of the vascular bed was observed. In our patient population, sensory and autonomic denervation did not correlate with age, sex, type of mutation, or MRI involvement. We found an involvement of the peripheral nervous system in patients with CADASIL through the assessment of cutaneous somatic and autonomic nerves. The neurovascular derangement observed in the skin may reflect, although to a lesser extent, what happens in the CNS. © 2016 American Academy of Neurology.

Optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy in retinal nerve fiber layer measurements of glaucoma patients.

PubMed

Fanihagh, Farsad; Kremmer, Stephan; Anastassiou, Gerasimos; Schallenberg, Maurice

2015-01-01

To determine the correlations and strength of association between different imaging systems in analyzing the retinal nerve fiber layer (RNFL) of glaucoma patients: optical coherence tomography (OCT), scanning laser polarimetry (SLP) and confocal scanning laser ophthalmoscopy (CSLO). 114 eyes of patients with moderate open angle glaucoma underwent spectral domain OCT (Topcon SD-OCT 2000 and Zeiss Cirrus HD-OCT), SLP (GDx VCC and GDx Pro) and CSLO (Heidelberg Retina Tomograph, HRT 3). Correlation coefficients were calculated between the structural parameters yielded by these examinations. The quantitative relationship between the measured RNFL thickness globally and for the four regions (superior, inferior, nasal, temporal) were evaluated with different regression models for all used imaging systems. The strongest correlation of RNFL measurements was found between devices using the same technology like GDx VCC and GDx Pro as well as Topcon OCT and Cirrus OCT. In glaucoma patients, the strongest associations (R²) were found between RNFL measurements of the two optical coherence tomography devices Topcon OCT and Cirrus OCT (R² = 0.513) and between GDx VCC and GDx Pro (R² = 0.451). The results of the OCTs and GDX Pro also had a strong quantitative relationship (Topcon OCT R² = 0.339 and Cirrus OCT R² = 0.347). GDx VCC and the OCTs showed a mild to moderate association (Topcon OCT R² = 0.207 and Cirrus OCT R² = 0.258). The confocal scanning laser ophthalmoscopy (HRT 3) had the lowest association to all other devices (Topcon OCT R² = 0.254, Cirrus OCT R² = 0.158, GDx Pro R² = 0.086 and GDx VCC R² = 0.1). The measurements of the RNFL in glaucoma patients reveal a high correlation of OCT and GDx devices because OCTs can measure all major retinal layers and SLP can detect nerve fibers allowing a comparison between the results of this devices. However, CSLO by means of HRT topography can only measure height values of the retinal surface but it cannot distinguish between different retinal layers. This may explain the rather poor correlations and associations between CSLO measurements and those of all other imaging devices which makes it difficult to compare HRT 3 nerve fiber data. These correlations are important in clinical routine especially when different techniques are used in the follow-up of glaucoma patients.

Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans.

PubMed

Mano, Tadaaki; Iwase, Satoshi; Toma, Shinobu

2006-11-01

Microneurography is a method using metal microelectrodes to investigate directly identified neural traffic in myelinated as well as unmyelinated efferent and afferent nerves leading to and coming from muscle and skin in human peripheral nerves in situ. The present paper reviews how this technique has been used in clinical neurophysiology to elucidate the neural mechanisms of autonomic regulation, motor control and sensory functions in humans under physiological and pathological conditions. Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task. Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion. Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain. Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch. No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans.

Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis

PubMed Central

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

2016-01-01

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

Diattenuation of brain tissue and its impact on 3D polarized light imaging

PubMed Central

Menzel, Miriam; Reckfort, Julia; Weigand, Daniel; Köse, Hasan; Amunts, Katrin; Axer, Markus

2017-01-01

3D-polarized light imaging (3D-PLI) reconstructs nerve fibers in histological brain sections by measuring their birefringence. This study investigates another effect caused by the optical anisotropy of brain tissue – diattenuation. Based on numerical and experimental studies and a complete analytical description of the optical system, the diattenuation was determined to be below 4 % in rat brain tissue. It was demonstrated that the diattenuation effect has negligible impact on the fiber orientations derived by 3D-PLI. The diattenuation signal, however, was found to highlight different anatomical structures that cannot be distinguished with current imaging techniques, which makes Diattenuation Imaging a promising extension to 3D-PLI. PMID:28717561

Nerve supply to the internal anal sphincter differs from that to the distal rectum: an immunohistochemical study of cadavers.

PubMed

Kinugasa, Yusuke; Arakawa, Takashi; Murakami, Gen; Fujimiya, Mineko; Sugihara, Kenichi

2014-04-01

Fecal incontinence is a common problem after anal sphincter-preserving operations. The intersphincteric autonomic nerves supplying the internal anal sphincter (IAS) are formed by the union of: (1) nerve fibers from Auerbach's nerve plexus of the most distal part of the rectum and (2) the inferior rectal branches of the pelvic plexus (IRB-PX) running along the conjoint longitudinal muscle coat. The aim of the present study is to identify the detailed morphology of nerves to the IAS. The study comprised histological and immunohistochemical evaluations of paraffin-embedded sections from a large block of anal canal from the preserved 10 cadavers. The IRB-PX came from the superior aspect of the levator ani and ran into the anal canal on the anterolateral side. These nerves contained both sympathetic and parasympathetic fibers, but the sympathetic content was much higher than in nerves from the distal rectum. All intramural ganglion cells in the distal rectum were neuronal nitric oxide synthase-positive and tyrosine hydroxylase-negative and were restricted to above the squamous-columnar epithelial junction. Parasympathetic nerves formed a lattice-like plexus in the circular smooth muscles of the distal rectum, whereas the IAS contained short, longitudinally running sympathetic and parasympathetic nerves, although sympathetic nerves were dominant. The major autonomic nerve input to the IAS seemed not to originate from the distal rectum but from the IRB-PX. Injury to the IRB-PX during surgery seemed to result in loss of innervation to the major part of the IAS.

Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

NASA Astrophysics Data System (ADS)

Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

2014-08-01

Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

Internal-Specific Morphological Analysis of Sciatic Nerve Fibers in a Radiofrequency-Induced Animal Neuropathic Pain Model

PubMed Central

Choi, Samjin; Choi, Hyuk Jai; Cheong, Youjin; Lim, Young-Jin; Park, Hun-Kuk

2013-01-01

This study investigated the reversible effects of pulsed radiofrequency (PRF) treatment at 42°C on the ultrastructural and biological changes in nerve and collagen fibers in the progression of neuropathic pain after rat sciatic nerve injury. Assessments of morphological changes in the extracellular matrices by atomic force microscopy and hematoxylin-eosin, Masson’s trichrome and picrosirius-red staining as well as the expressions of two fibril-forming collagens, types-I and -III, and two inflammatory cytokines, TNF-α and IL-6, were evaluated on day 30 after RF exposure. There were four groups for different RF thermal treatments: no treatment, no current, PRF, and continuous RF (CRF). An RF procedure similar to that used in human clinical trials was used in this study. The CRF treatment at 82°C led to neural and collagen damage by the permanent blockage of sensory nociceptors. The PRF treatment led to excellent performance and high expandability compared to CRF, with effects including slight damage and swelling of myelinated axons, a slightly decreased amount of collagen fibers, swelling of collagen fibril diameters, decreased immunoreactivity of collagen types-I and -III, presence of newly synthesized collagen, and recovery of inflammatory protein immunoreactivity. These evidence-based findings suggest that PRF-based pain relief is responsible for the temporary blockage of nerve signals as well as the preferential destruction of pain-related principal sensory fibers like the Aδ and C fibers. This suggestion can be supported by the interaction between the PRF-induced electromagnetic field and cell membranes; therefore, PRF treatment provides pain relief while allowing retention of some tactile sensation. PMID:24066083

Trophic specificity of the gustatory fibers upon taste bud regeneration.

PubMed

State, F A; Hamed, M S; El-Hashash, M K; Gaber, O M

1982-01-01

24 adult dogs were classified into six groups; in 2 animals of each group the lingual nerve was transected distal to the point of entry of the chorda tympani and its proximal end was sutured to the distal end of the glossopharyngeal nerve. In the other 2 animals transtympanic chorda tympani neurectomy was performed before suturing the lingual and glossopharyngeal nerves. Invasion of the papillae by regenerating fibers from the 8th postoperative week onwards was followed by reappearance of taste buds only in lingual glossopharyngeal anastomosis with intact chorda tympani. The difference in number of taste buds, size and number of constituent cells between the two operative procedures was statistically significant from the 8th week onwards. The significance of these findings was discussed.

The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus.

PubMed

Ishibashi, Fukashi; Kojima, Rie; Taniguchi, Miki; Kosaka, Aiko; Uetake, Harumi; Tavakoli, Mitra

2016-01-01

This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia-induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients.

The vagus and recurrent laryngeal nerves in the rodent experimental model of esophageal atresia.

PubMed

Qi, B Q; Merei, J; Farmer, P; Hasthorpe, S; Myers, N A; Beasley, S W; Hutson, J M

1997-11-01

After surgical correction of their esophageal atresia and tracheoesophageal fistula (EA-TEF), many patients exhibit evidence of esophageal dysmotility. Controversy exists as to whether the esophageal motility disorders result from denervation caused by surgery or from an inherent abnormal innervation of the esophagus. The present study used an Adriamycin-induced EA-TEF fetal rat model to trace the course and branching of both the vagus and recurrent laryngeal nerves. Abnormalities observed in EA-TEF rat fetuses include: (1) fewer branches from both recurrent laryngeal nerves; (2) deviation of the left vagus from its normal course below the aorta, passing behind the fistula to approach and join with the right vagus to form a single nerve trunk on the right side of the esophagus; (3) relatively few branches from the single vagal nerve trunk (composed of fibers of the left and the right vagus) on the surface of the lower esophagus. Fetuses affected by EA-TEF have inherent abnormalities in the course and branching pattern of the vagus nerves as they descend through the thorax, culminating in a deficient extrinsic nerve fiber plexus in the lower esophagus. These observations may account for the esophageal motility disorders seen in patients who have EA-TEF even before surgical intervention.

Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1.

PubMed

Lee, Yi-Chen; Lu, Shui-Chin; Hsieh, Yu-Lin

2018-02-13

Patients with diabetes mellitus (DM) or those experiencing the neurotoxic effects of chemotherapeutic agents may develop sensation disorders due to degeneration and injury of small-diameter sensory neurons, referred to as small fiber neuropathy. Present animal models of small fiber neuropathy affect both large- and small-diameter sensory fibers and thus create a neuropathology too complex to properly assess the effects of injured small-diameter sensory fibers. Therefore, it is necessary to develop an experimental model of pure small fiber neuropathy to adequately examine these issues. This protocol describes an experimental model of small fiber neuropathy specifically affecting small-diameter sensory nerves with resiniferatoxin (RTX), an ultrapotent agonist of transient receptor potential vanilloid type 1 (TRPV1), through a single dose of intraperitoneal injection, referred to as RTX neuropathy. This RTX neuropathy showed pathological manifestations and behavioral abnormalities that mimic the clinical characteristics of patients with small fiber neuropathy, including intraepidermal nerve fiber (IENF) degeneration, specifically injury in small-diameter neurons, and induction of thermal hypoalgesia and mechanical allodynia. This protocol tested three doses of RTX (200, 50, and 10 µg/kg, respectively) and concluded that a critical dose of RTX (50 µg/kg) is required for the development of typical small fiber neuropathy manifestations, and prepared a modified immunostaining procedure to investigate IENF degeneration and neuronal soma injury. The modified procedure is fast, systematic, and economic. Behavioral evaluation of neuropathic pain is critical to reveal the function of small-diameter sensory nerves. The evaluation of mechanical thresholds in experimental rodents is particularly challenging and this protocol describes a customized metal mesh that is suitable for this type of assessment in rodents. In summary, RTX neuropathy is a new and easily established experimental model to evaluate the molecular significance and intervention underlying neuropathic pain for the development of therapeutic agents.

Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth

NASA Astrophysics Data System (ADS)

Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

2016-05-01

The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ~1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ~1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01169a

MYONEURAL JUNCTIONS OF TWO ULTRASTRUCTURALLY DISTINCT TYPES IN EARTHWORM BODY WALL MUSCLE

PubMed Central

Rosenbluth, Jack

1972-01-01

The longitudinal muscle of the earthworm body wall is innervated by nerve bundles containing axons of two types which form two corresponding types of myoneural junction with the muscle fibers Type I junctions resemble cholinergic neuromuscular junctions of vertebrate skeletal muscle and are characterized by three features: (a) The nerve terminals contain large numbers of spherical, clear, ∼500 A vesicles plus a small number of larger dense-cored vesicles (b) The junctional gap is relatively wide (∼900 A), and it contains a basement membrane-like material, (c) The postjunctional membrane, although not folded, displays prominent specializations on both its external and internal surfaces The cytoplasmic surface is covered by a dense matrix ∼200 A thick which appears to be the site of insertion of fine obliquely oriented cytoplasmic filaments The external surface exhibits rows of projections ∼200 A long whose bases consist of hexagonally arrayed granules seated in the outer dense layer of the plasma membrane The concentration of these hexagonally disposed elements corresponds to the estimated concentration of both receptor sites and acetylcholinesterase sites at cholinergic junctions elsewhere. Type II junctions resemble the adrenergic junctions in vertebrate smooth muscle and exhibit the following structural characteristics: (a) The nerve fibers contain predominantly dense-cored vesicles ∼1000 A in diameter (b) The junctional gap is relatively narrow (∼150 A) and contains no basement membrane-like material, (c) Postjunctional membrane specialization is minimal. It is proposed that the structural differences between the two types of myoneural junction reflect differences in the respective transmitters and corresponding differences in the mechanisms of transmitter action and/or inactivation. PMID:5044759

Comparison of diagnostic capability of macular ganglion cell complex and retinal nerve fiber layer among primary open angle glaucoma, ocular hypertension, and normal population using Fourier-domain optical coherence tomography and determining their functional correlation in Indian population

PubMed Central

Barua, Nabanita; Sitaraman, Chitra; Goel, Sonu; Chakraborti, Chandana; Mukherjee, Sonai; Parashar, Hemandra

2016-01-01

Context: Analysis of diagnostic ability of macular ganglionic cell complex and retinal nerve fiber layer (RNFL) in glaucoma. Aim: To correlate functional and structural parameters and comparing predictive value of each of the structural parameters using Fourier-domain (FD) optical coherence tomography (OCT) among primary open angle glaucoma (POAG) and ocular hypertension (OHT) versus normal population. Setting and Design: Single centric, cross-sectional study done in 234 eyes. Materials and Methods: Patients were enrolled in three groups: POAG, ocular hypertensive and normal (40 patients in each group). After comprehensive ophthalmological examination, patients underwent standard automated perimetry and FD-OCT scan in optic nerve head and ganglion cell mode. The relationship was assessed by correlating ganglion cell complex (GCC) parameters with mean deviation. Results were compared with RNFL parameters. Statistical Analysis: Data were analyzed with SPSS, analysis of variance, t-test, Pearson's coefficient, and receiver operating curve. Results: All parameters showed strong correlation with visual field (P < 0.001). Inferior GCC had highest area under curve (AUC) for detecting glaucoma (0.827) in POAG from normal population. However, the difference was not statistically significant (P > 0.5) when compared with other parameters. None of the parameters showed significant diagnostic capability to detect OHT from normal population. In diagnosing early glaucoma from OHT and normal population, only inferior GCC had statistically significant AUC value (0.715). Conclusion: In this study, GCC and RNFL parameters showed equal predictive capability in perimetric versus normal group. In early stage, inferior GCC was the best parameter. In OHT population, single day cross-sectional imaging was not valuable. PMID:27221682

Electrospun nerve guide scaffold of poly(ε-caprolactone)/collagen/nanobioglass: an in vitro study in peripheral nerve tissue engineering.

PubMed

Mohamadi, Forouzan; Ebrahimi-Barough, Somayeh; Reza Nourani, Mohammad; Ali Derakhshan, Mohammad; Goodarzi, Vahabodin; Sadegh Nazockdast, Mohammad; Farokhi, Mehdi; Tajerian, Roksana; Faridi Majidi, Reza; Ai, Jafar

2017-07-01

Among various methods, nerve tissue engineering (NTE) is one of the applicable methods to reconstruct damaged nerve tissues. Electrospinning technique and biomaterials are often considered to fabricate fibrous tissue engineered conduits which have great similarity to the extracellular matrix on fiber structure. Polymer blending is one of the most effective methods for the production of new materials with outstanding features. In this study, conduit structures as main part of the peripheral nerve regeneration based on polymer blend nanocomposites poly(ε-caprolactone)/collagen/nanobioglass (PCL/collagen/NBG) were manufactured by electrospinning technique. Various properties of electrospun mats were investigated by using contact angle, tensile, degradation time, porosity, scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and wide-angle X-ray scattering (WAXS). The SEM analysis was shown that size range and average pore size of polymer blend nanocomposite nanofibers were about 250-400 nm and 0.7 µm, respectively, with an optimum porosity of 62.5%. The XRD result was shown that synthesized nanoparticles of NBG had amorphous structures. Also, FTIR analysis indicated that good interaction between polymer-polymer macromolecules and polymer particles. The contact angle and tensile tests were indicated that electrospun webs showed good hydrophilicity and toughness properties. According to SEM, MTT assay and DAPI staining technique, the ability to support cell attachment and viability of samples were characterized. In vitro study indicated electrospun collagen/PCL/NBG nanofibrous conduit promoted Human Endometrial Stem cells (hEnSCs) adhesion and proliferation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1960-1972, 2017. © 2017 Wiley Periodicals, Inc.

Optical stimulation of the facial nerve: a surgical tool?

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Teudt, Ingo Ulrik; Nevel, Adam E.; Izzo, Agnella D.; Walsh, Joseph T., Jr.

2008-02-01

One sequela of skull base surgery is the iatrogenic damage to cranial nerves. Devices that stimulate nerves with electric current can assist in the nerve identification. Contemporary devices have two main limitations: (1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue. Stimulation and screening of the nerve is possible without making physical contact. The gerbil facial nerve was irradiated with 250-μs-long pulses of 2.12 μm radiation delivered via a 600-μm-diameter optical fiber at a repetition rate of 2 Hz. Muscle action potentials were recorded with intradermal electrodes. Nerve samples were examined for possible tissue damage. Eight facial nerves were stimulated with radiant exposures between 0.71-1.77 J/cm2, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3-0.4 mV, 0.15-1.4 mV and 0.3-2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm2, but no apparent damage at radiant exposures of 2.0 J/cm2.

Macroscopic in vivo imaging of facial nerve regeneration in Thy1-GFP rats.

PubMed

Placheta, Eva; Wood, Matthew D; Lafontaine, Christine; Frey, Manfred; Gordon, Tessa; Borschel, Gregory H

2015-01-01

Facial nerve injury leads to severe functional and aesthetic deficits. The transgenic Thy1-GFP rat is a new model for facial nerve injury and reconstruction research that will help improve clinical outcomes through translational facial nerve injury research. To determine whether serial in vivo imaging of nerve regeneration in the transgenic rat model is possible, facial nerve regeneration was imaged under the main paradigms of facial nerve injury and reconstruction. Fifteen male Thy1-GFP rats, which express green fluorescent protein (GFP) in their neural structures, were divided into 3 groups in the laboratory: crush-injury, direct repair, and cross-face nerve grafting (30-mm graft length). The distal nerve stump or nerve graft was predegenerated for 2 weeks. The facial nerve of the transgenic rats was serially imaged at the time of operation and after 2, 4, and 8 weeks of regeneration. The imaging was performed under a GFP-MDS-96/BN excitation stand (BLS Ltd). Facial nerve injury. Optical fluorescence of regenerating facial nerve axons. Serial in vivo imaging of the regeneration of GFP-positive axons in the Thy1-GFP rat model is possible. All animals survived the short imaging procedures well, and nerve regeneration was followed over clinically relevant distances. The predegeneration of the distal nerve stump or the cross-face nerve graft was, however, necessary to image the regeneration front at early time points. Crush injury was not suitable to sufficiently predegenerate the nerve (and to allow for degradation of the GFP through Wallerian degeneration). After direct repair, axons regenerated over the coaptation site in between 2 and 4 weeks. The GFP-positive nerve fibers reached the distal end of the 30-mm-long cross-face nervegrafts after 4 to 8 weeks of regeneration. The time course of facial nerve regeneration was studied by serial in vivo imaging in the transgenic rat model. Nerve regeneration was followed over clinically relevant distances in a small number of experimental animals, as they were subsequently imaged at multiple time points. The Thy1-GFP rat model will help improve clinical outcomes of facial reanimation surgery through improving the knowledge of facial nerve regeneration after surgical procedures. NA.

A test of a linear model of glaucomatous structure-function loss reveals sources of variability in retinal nerve fiber and visual field measurements.

PubMed

Hood, Donald C; Anderson, Susan C; Wall, Michael; Raza, Ali S; Kardon, Randy H

2009-09-01

Retinal nerve fiber (RNFL) thickness and visual field loss data from patients with glaucoma were analyzed in the context of a model, to better understand individual variation in structure versus function. Optical coherence tomography (OCT) RNFL thickness and standard automated perimetry (SAP) visual field loss were measured in the arcuate regions of one eye of 140 patients with glaucoma and 82 normal control subjects. An estimate of within-individual (measurement) error was obtained by repeat measures made on different days within a short period in 34 patients and 22 control subjects. A linear model, previously shown to describe the general characteristics of the structure-function data, was extended to predict the variability in the data. For normal control subjects, between-individual error (individual differences) accounted for 87% and 71% of the total variance in OCT and SAP measures, respectively. SAP within-individual error increased and then decreased with increased SAP loss, whereas OCT error remained constant. The linear model with variability (LMV) described much of the variability in the data. However, 12.5% of the patients' points fell outside the 95% boundary. An examination of these points revealed factors that can contribute to the overall variability in the data. These factors include epiretinal membranes, edema, individual variation in field-to-disc mapping, and the location of blood vessels and degree to which they are included by the RNFL algorithm. The model and the partitioning of within- versus between-individual variability helped elucidate the factors contributing to the considerable variability in the structure-versus-function data.

Cranial Pair 0: The Nervus Terminalis.

PubMed

PeñA-Melian, Angel; Cabello-de la Rosa, Juan Pablo; Gallardo-Alcañiz, Maria Jose; Vaamonde-Gamo, Julia; Relea-Calatayud, Fernanda; Gonzalez-Lopez, Lucia; Villanueva-Anguita, Patricia; Flores-Cuadrado, Alicia; Saiz-Sanchez, Daniel; Martinez-Marcos, Alino

2018-04-16

Originally discovered in elasmobranchs by Fritsh in 1878, the nervus terminalis has been found in virtually all species, including humans. After more than one-century debate on its nomenclature, it is nowadays recognized as cranial pair zero. The nerve mostly originates in the olfactory placode, although neural crest contribution has been also proposed. Developmentally, the nervus terminalis is clearly observed in human embryos; subsequently, during the fetal period loses some of its ganglion cells, and it is less recognizable in adults. Fibers originating in the nasal cavity passes into the cranium through the middle area of the cribiform plate of the ethmoid bone. Intracranially, fibers joint the telencephalon at several sites including the olfactory trigone and the primordium of the hippocampus to reach preoptic and precommissural regions. The nervus terminalis shows ganglion cells, that sometimes form clusters, normally one or two located at the base of the crista galli, the so-called ganglion of the nervus terminalis. Its function is uncertain. It has been described that its fibers facilitates migration of luteinizing hormone-releasing hormone cells to the hypothalamus thus participating in the development of the hypothalamic-gonadal axis, which alteration may provoke Kallmann's syndrome in humans. This review summarizes current knowledge on this structure, incorporating original illustrations of the nerve at different developmental stages, and focuses on its anatomical and clinical relevance. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Application for the Drosophila ventral nerve cord standard in neuronal circuit reconstruction and in-depth analysis of mutant morphology

PubMed Central

Boerner, Jana; Godenschwege, Tanja Angela

2010-01-01

The Drosophila standard brain has been a useful tool that provides information about position and size of different brain structures within a wild-type brain and allows the comparison of imaging data that were collected from individual preparations. Therefore the standard can be used to reveal and visualize differences of brain regions between wild-type and mutant brains and can provide spatial description of single neurons within the nervous system. Recently the standard brain was complemented by the generation of a ventral nerve cord (VNC) standard. Here the authors have registered the major components of a simple neuronal circuit, the Giant Fiber System (GFS), into this standard. The authors show that they can also virtually reconstruct the well-characterized synaptic contact of the Giant Fiber with its motorneuronal target when they register the individual neurons from different preparations into the VNC standard. In addition to the potential application for the standard thorax in neuronal circuit reconstruction, the authors show that it is a useful tool for in-depth analysis of mutant morphology of single neurons. The authors find quantitative and qualitative differences when they compared the Giant Fibers of two different neuroglian alleles, nrg849 and nrgG00305, using the averaged wild-type GFS in the standard VNC as a reference. PMID:20615087

Electrophysiological abnormalities associated with extensive myelinated retinal nerve fibers

PubMed Central

Tay, Su Ann; Sanjay, Srinivasan

2012-01-01

An observational case report of electrophysiological abnormalities in a patient with anisomyopic amblyopia as a result of unilateral extensive myelinated retinal nerve fibers (MNFs) is illustrated. The electrophysiological readings revealed an abnormal pattern electroretinogram (PERG) but normal full-field electroretinogram readings in the affected eye. The visual-evoked potential was also undetectable in that eye. Our findings suggest that extensive MNFs can be associated with electrophysiological abnormalities, in particular the PERG, which can aid in diagnosing the cause of impaired vision when associated with amblyopia. PMID:22824610

AXOPLASMIC PROTEINS OF THE SQUID GIANT NERVE FIBER WITH PARTICULAR REFERENCE TO THE FIBROUS PROTEIN

PubMed Central

Maxfield, Myles

1953-01-01

1. Axoplasm of squid giant nerve fibers is examined with the ultracentrifuge and electrophoresis apparatus and several distinct components demonstrated. 2. One of these components, a protein called axon filaments, is isolated by fractional extraction followed by differential ultracentrifugation and redissolving in glycine solution. Axon filaments are monodisperse by ultracentrifugation. Their physical chemical properties have been studied. 3. The existence of a reversible transformation of axon filaments into a particle of lower molecular weight and lower asymmetry has been demonstrated. PMID:13109156

Imaging the Facial Nerve: A Contemporary Review

PubMed Central

Gupta, Sachin; Mends, Francine; Hagiwara, Mari; Fatterpekar, Girish; Roehm, Pamela C.

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. PMID:23766904

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

PubMed

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

2016-02-01

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

The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

PubMed

Kamo, Atsuko; Tominaga, Mitsutoshi; Kamata, Yayoi; Kaneda, Kazuyuki; Ko, Kyi C; Matsuda, Hironori; Kimura, Utako; Ogawa, Hideoki; Takamori, Kenji

2014-12-01

Epidermal hyperinnervation, which is thought to underlie intractable pruritus, has been observed in patients with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. Previously, we showed that the excimer lamp has antihyperinnervative effects in nonpruritic dry-skin model mice, although epidermal expression of axonal guidance molecules was unchanged. Therefore, we investigated the antipruritic effects of excimer lamp irradiation and its mechanism of action. A single irradiation of AD model mice significantly inhibited itch-related behavior 1 day later, following improvement in the dermatitis score. In addition, irradiation of nerve fibers formed by cultured dorsal root ganglion neurons increased bleb formation and decreased nerve fiber expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting degenerative changes in these fibers. We also analyzed whether attaching a cutoff excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA damage marker, in dry-skin model mice. Irradiation with COF decreased CPD production in keratinocytes, as well as having an antihyperinnervative effect, indicating that the antipruritic effects of excimer lamp irradiation with COF are due to induction of epidermal nerve degeneration and reduced DNA damage.

Pudendal nerve in pelvic bone fractures.

PubMed

Báča, Václav; Báčová, Tereza; Grill, Robert; Otčenášek, Michal; Kachlík, David; Bartoška, Radek; Džupa, Valér

2013-07-01

Pelvic ring injuries rank among the most serious skeletal injuries. According to published data, pelvic fractures constitute 3-8% of all fractures. There has been a threefold increase in the number of these fractures over the last 10 years. A significant factor determining the choice of the therapeutic procedure, timing and sequence of individual steps, and also the prognosis of the patient with a fractured pelvis, are associated injuries defined as injuries to the organs and anatomical structures found in the pelvic region. Published data describes the incidence of injury to neurogenic structures as ranging between 9 and 21%, to the urogenital tract between 5 and 11%, to the gastrointestinal tract in 3-17% and to the gynecologic organs up to 1%. The pathway of the pudendal nerve may be affected in types B and C fractures where the root fibers emerge from the foramina sacralia and plexus sacralis is formed, on the one hand, and in types A, B and C fractures during the nerve's course alongside the inferior pubic ramus. In order to determine the frequency of potential injury to the pudendal nerve, a set of 225 pelvic fractures treated between 2007 and 2009 was assessed; 38 fixed hemipelves were also used to study the length of the course of the pudendal nerve alongside the inferior pubic ramus, on the one hand, and the distances from the symphysis pubica at the crossing of the branches of the n. pudendus-n. dorsalis penis and the branches for the muscles of the diaphragma urogenitale on the other hand. The work elucidated the selected distances and discuss their possible clinical relevance for evaluation of the seriousness of pelvic fractures from the perspective of late sequelae in the region innervated by the pudendal nerve. Copyright © 2012 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freitas, Ricardo Miguel Costa de, E-mail: ricardomcfreitas@gmail.com; Andrade, Celi Santos, E-mail: celis.andrade@hotmail.com; Caldas, José Guilherme Mendes Pereira, E-mail: jgmpcaldas@uol.com.br

PurposeThis study was designed to present the feasibility of an in vivo image-guided percutaneous cryoablation of the porcine vertebral body.MethodsThe institutional animal care committee approved this study. Cone-beam computed tomography (CBCT)-guided vertebral cryoablations (n = 22) were performed in eight pigs with short, 2-min, single or double-freezing protocols. Protective measures to nerves included dioxide carbon (CO{sub 2}) epidural injections and spinal canal temperature monitoring. Clinical, radiological, and pathological data with light (n = 20) or transmission electron (n = 2) microscopic analyses were evaluated after 6 days of clinical follow-up and euthanasia.ResultsCBCT/fluoroscopic-guided transpedicular vertebral body cryoprobe positioning and CO{sub 2} epidural injection were successful in all procedures. No majormore » complications were observed in seven animals (87.5 %, n = 8). A minor complication was observed in one pig (12.5 %, n = 1). Logistic regression model analysis showed the cryoprobe-spinal canal (Cp-Sc) distance as the most efficient parameter to categorize spinal canal temperatures lower than 19 °C (p < 0.004), with a significant Pearson’s correlation test (p < 0.041) between the Cp-Sc distance and the lowest spinal canal temperatures. Ablation zones encompassed pedicles and the posterior wall of the vertebral bodies with an inflammatory rim, although no inflammatory infiltrate was depicted in the surrounding neural structures at light microscopy. Ultrastructural analyses evidenced myelin sheath disruption in some large nerve fibers, although neurological deficits were not observed.ConclusionsCBCT-guided vertebral cryoablation of the porcine spine is feasible under a combination of a short freezing protocol and protective measures to the surrounding nerves. Ultrastructural analyses may be helpful assess the early modifications of the nerve fibers.« less

Neurogenin 1 Null Mutant Ears Develop Fewer, Morphologically Normal Hair Cells in Smaller Sensory Epithelia Devoid of Innervation

PubMed Central

Ma, Qiufu; Anderson, David J.

2000-01-01

The proneuronal gene neurogenin 1 (ngn1) is essential for development of the inner-ear sensory neurons that are completely absent in ngn1 null mutants. Neither afferent, efferent, nor autonomic nerve fibers were detected in the ears of ngn1 null mutants. We suggest that efferent and autonomic fibers are lost secondarily to the absence of afferents. In this article we show that ngn1 null mutants develop smaller sensory epithelia with morphologically normal hair cells. In particular, the saccule is reduced dramatically and forms only a small recess with few hair cells along a duct connecting the utricle with the cochlea. Hair cells of newborn ngn1 null mutants show no structural abnormalities, suggesting that embryonic development of hair cells is independent of innervation. However, the less regular pattern of dispersal within sensory epithelia may be caused by some effects of afferents or to the stunted growth of the sensory epithelia. Tracing of facial and stato-acoustic nerves in control and ngn1 null mutants showed that only the distal, epibranchial, placode-derived sensory neurons of the geniculate ganglion exist in mutants. Tracing further showed that these geniculate ganglion neurons project exclusively to the solitary tract. In addition to the normal complement of facial branchial and visceral motoneurons, ngn1 null mutants have some trigeminal motoneurons and contralateral inner-ear efferents projecting, at least temporarily, through the facial nerve. These data suggest that some neurons in the brainstem (e.g., inner-ear efferents, trigeminal motoneurons) require afferents to grow along and redirect to ectopic cranial nerve roots in the absence of their corresponding sensory roots. PMID:11545141

THE FINE STRUCTURE OF MEISSNER's TOUCH CORPUSCLES OF HUMAN FINGERS

PubMed Central

Cauna, Nikolajs; Ross, Leonard L.

1960-01-01

Thin slices of the finger pads of six individuals were fixed in buffered 1 per cent osmic acid, embedded in deaerated, nitrogenated methacrylate, and cut into thin sections for electron microscopic study. Before embedding, the slices were trimmed so as to include several digital tactile corpuscles. Some thin sections were stained in 10 per cent aqueous phosphotungstic acid solution. The principal part of Meissner's corpuscle is made up of flattened laminar cells stretching across the corpuscle in irregular layers. The perinuclear cytoplasm of these cells contains numerous small mitochondria, a sparse granular endoplasmic reticulum, and a large number of small vesicles. Nerve fibers enter the side or base of the corpuscle, lose their myelin sheaths, and follow a meandering course between the laminar cell plates. The nerve endings enter into a close appositional relationship with the flattened portions of the laminar cells. In some areas the apposed axolemma and cell membranes are slightly thickened with small vesicles located along the cell membrane or on both surfaces. These regions are interpreted as synapses. The most prominent feature of the nerve endings is an extraordinary accumulation of small mitochondria which vary in size and internal density. The nerve endings also contain vacuoles, groups of dense concentric membranes, and small dense vesicles of irregular distribution. The laminar cells are separated from one another by a dense intercellular substance of uniform thickness which also envelops the entire corpuscle. This material contains randomly oriented collagen fibers and fine fibrils bound together by a dense material at nodal points recurring at regular intervals of approximately 120 mµ. These findings are discussed in relation to the problems of the function of Meissner's corpuscle, neural material loss and replacement, and the presence of synapses. PMID:13691669

Image-Guided Cryoablation of the Spine in a Swine Model: Clinical, Radiological, and Pathological Findings with Light and Electron Microscopy.

PubMed

de Freitas, Ricardo Miguel Costa; Andrade, Celi Santos; Caldas, José Guilherme Mendes Pereira; Tsunemi, Miriam Harumi; Ferreira, Lorraine Braga; Arana-Chavez, Victor Elias; Cury, Patrícia Maluf

2015-10-01

This study was designed to present the feasibility of an in vivo image-guided percutaneous cryoablation of the porcine vertebral body. The institutional animal care committee approved this study. Cone-beam computed tomography (CBCT)-guided vertebral cryoablations (n = 22) were performed in eight pigs with short, 2-min, single or double-freezing protocols. Protective measures to nerves included dioxide carbon (CO2) epidural injections and spinal canal temperature monitoring. Clinical, radiological, and pathological data with light (n = 20) or transmission electron (n = 2) microscopic analyses were evaluated after 6 days of clinical follow-up and euthanasia. CBCT/fluoroscopic-guided transpedicular vertebral body cryoprobe positioning and CO2 epidural injection were successful in all procedures. No major complications were observed in seven animals (87.5 %, n = 8). A minor complication was observed in one pig (12.5 %, n = 1). Logistic regression model analysis showed the cryoprobe-spinal canal (Cp-Sc) distance as the most efficient parameter to categorize spinal canal temperatures lower than 19 °C (p < 0.004), with a significant Pearson's correlation test (p < 0.041) between the Cp-Sc distance and the lowest spinal canal temperatures. Ablation zones encompassed pedicles and the posterior wall of the vertebral bodies with an inflammatory rim, although no inflammatory infiltrate was depicted in the surrounding neural structures at light microscopy. Ultrastructural analyses evidenced myelin sheath disruption in some large nerve fibers, although neurological deficits were not observed. CBCT-guided vertebral cryoablation of the porcine spine is feasible under a combination of a short freezing protocol and protective measures to the surrounding nerves. Ultrastructural analyses may be helpful assess the early modifications of the nerve fibers.

Three Hierarchies in Skeletal Muscle Fibre Classification Allotype, Isotype and Phenotype

NASA Technical Reports Server (NTRS)

Hoh, Joseph F. Y.; Hughes, Suzanne; Hugh, Gregory; Pozgaj, Irene

1991-01-01

Immunocytochemical analyses using specific anti-myosin antibodies of mammalian muscle fibers during regeneration, development, and after denervation have revealed two distinct myogenic components determining fiber phenotype. The jaw-closing muscles of the cat contain superfast fibers which express a unique myosin not found in limb muscles. When superfast muscle is transplanted into a limb muscle bed, regenerating myotubes synthesize superfast myosin independent of innervation. Reinnervation by the nerve to a fast muscle leads to the expression of superfast and not fast myosin, while reinnervation by the nerve to a slow muscle leads to the expression of a slow myosin. When limb muscle is transplanted into the jaw muscle bed, only limb myosins are synthesized. Thus jaw and limb muscles belong to distinct allotypes, each with a unique range of phenotype options, the expressions of which may be modulated by the nerve. Primary and secondary myotubes in developing jaw and limb muscles are observed to belong to different categories characterized by different patterns of myosin gene expression. By taking into consideration the pattern of myosins synthesized and the changes in fiber size after denervation, 3 types of primary (fast, slow, and intermediate) fibers can be distinguished in rat fast limb muscles. All primaries synthesize slow myosin soon after their formation, but this is withdrawn in fast and intermediate primaries at different times. After neonatal denervation, slow and intermediate primaries express slow primaries hypertrophy with other fibers atrophy. In the mature rat, the number of slow fibers in the EDL is less than the number of slow primaries. Upon denervation, hypertrophic slow fibers matching the number and topographic distribution of slow primaries appear, suggesting that a subpopulation of the slow primaries acquire the fast phenotype during adult life, but reveal their original identity as slow primaries in response to denervation by hypertrophying and synthesizing slow myosin. It is proposed that within each muscle allotype, the various isotypes of primary and secondary fibers are myogenically determined, and are derived from different lineage of myoblasts.

Gasserian Ganglion and Retrobulbar Nerve Block in the Treatment of Ophthalmic Postherpetic Neuralgia: A Case Report.

PubMed

Huang, Jie; Ni, Zhongge; Finch, Philip

2017-09-01

Varicella zoster virus reactivation can cause permanent histological changes in the central and peripheral nervous system. Neural inflammatory changes or damage to the dorsal root ganglia sensory nerve fibers during reactivation can lead to postherpetic neuralgia (PHN). For PHN of the first division of the fifth cranial nerve (ophthalmic division of the trigeminal ganglion), there is evidence of inflammatory change in the ganglion and adjacent ocular neural structures. First division trigeminal nerve PHN can prove to be difficult and sometimes even impossible to manage despite the use of a wide range of conservative measures, including anticonvulsant and antidepressant medication. Steroids have been shown to play an important role by suppressing neural inflammatory processes. We therefore chose the trigeminal ganglion as an interventional target for an 88-year-old woman with severe ophthalmic division PHN after she failed to respond to conservative treatment. Under fluoroscopic guidance, a trigeminal ganglion nerve block was performed with lidocaine combined with dexamethasone. A retrobulbar block with lidocaine and triamcinolone settled residual oculodynia. At 1-year follow-up, the patient remained pain free and did not require analgesic medication. To our knowledge, this is the first reported case of ophthalmic division PHN successfully treated with a combination of trigeminal ganglion and retrobulbar nerve block using a local anesthetic agent and steroid for central and peripheral neural inflammatory processes. © 2016 World Institute of Pain.

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

PubMed Central

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

2014-01-01

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

Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers.

PubMed

Laedermann, Cédric J; Pertin, Marie; Suter, Marc R; Decosterd, Isabelle

2014-03-11

Dysregulation of voltage-gated sodium channels (Na(v)s) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization of the different isoforms of Na(v)s under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Na(v)s mRNA levels in mouse dorsal root ganglia (DRG) were studied in the spared nerve injury (SNI) and spinal nerve ligation (SNL) models of neuropathic pain. In the SNI model, injured and non-injured neurons were intermingled in lumbar DRG, which were pooled to increase the tissue available for experiments. A strong downregulation was observed for every Na(v)s isoform expressed except for Na(v)1.2; even Na(v)1.3, known to be upregulated in rat neuropathic pain models, was lower in the SNI mouse model. This suggests differences between these two species. In the SNL model, where the cell bodies of injured and non-injured fibers are anatomically separated between different DRG, most Na(v)s were observed to be downregulated in the L5 DRG receiving axotomized fibers. Transcription was then investigated independently in the L3, L4 and L5 DRG in the SNI model, and an important downregulation of many Na(v)s isoforms was observed in the L3 DRG, suggesting the presence of numerous injured neurons there after SNI. Consequently, the proportion of axotomized neurons in the L3, L4 and L5 DRG after SNI was characterized by studying the expression of activating transcription factor 3 (ATF3). Using this marker of nerve injury confirmed that most injured fibers find their cell bodies in the L3 and L4 DRG after SNI in C57BL/6 J mice; this contrasts with their L4 and L5 DRG localization in rats. The spared sural nerve, through which pain hypersensitivity is measured in behavioral studies, mostly projects into the L4 and L5 DRG. The complex regulation of Na(v)s, together with the anatomical rostral shift of the DRG harboring injured fibers in C57BL/6 J mice, emphasize that caution is necessary and preliminary anatomical experiments should be carried out for gene and protein expression studies after SNI in mouse strains.

Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers

PubMed Central

2014-01-01

Background Dysregulation of voltage-gated sodium channels (Navs) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization of the different isoforms of Navs under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Navs mRNA levels in mouse dorsal root ganglia (DRG) were studied in the spared nerve injury (SNI) and spinal nerve ligation (SNL) models of neuropathic pain. In the SNI model, injured and non-injured neurons were intermingled in lumbar DRG, which were pooled to increase the tissue available for experiments. Results A strong downregulation was observed for every Navs isoform expressed except for Nav1.2; even Nav1.3, known to be upregulated in rat neuropathic pain models, was lower in the SNI mouse model. This suggests differences between these two species. In the SNL model, where the cell bodies of injured and non-injured fibers are anatomically separated between different DRG, most Navs were observed to be downregulated in the L5 DRG receiving axotomized fibers. Transcription was then investigated independently in the L3, L4 and L5 DRG in the SNI model, and an important downregulation of many Navs isoforms was observed in the L3 DRG, suggesting the presence of numerous injured neurons there after SNI. Consequently, the proportion of axotomized neurons in the L3, L4 and L5 DRG after SNI was characterized by studying the expression of activating transcription factor 3 (ATF3). Using this marker of nerve injury confirmed that most injured fibers find their cell bodies in the L3 and L4 DRG after SNI in C57BL/6 J mice; this contrasts with their L4 and L5 DRG localization in rats. The spared sural nerve, through which pain hypersensitivity is measured in behavioral studies, mostly projects into the L4 and L5 DRG. Conclusions The complex regulation of Navs, together with the anatomical rostral shift of the DRG harboring injured fibers in C57BL/6 J mice, emphasize that caution is necessary and preliminary anatomical experiments should be carried out for gene and protein expression studies after SNI in mouse strains. PMID:24618114

Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo)

PubMed Central

Moeller, John F.; Meredith, Michael

2010-01-01

The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RFamide-like peptides. To define further the cell populations and connectivity, we used double-label immuno-cytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH immunoreactive (ir) cell-profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies, and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT) negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. PMID:20950589

Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo).

PubMed

Moeller, John F; Meredith, Michael

2010-12-17

The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. Copyright © 2010 Elsevier B.V. All rights reserved.

Role of intrahepatic innervation in regulating the activity of liver cells

PubMed Central

Streba, Letitia Adela Maria; Vere, Cristin Constantin; Ionescu, Alin Gabriel; Streba, Costin Teodor; Rogoveanu, Ion

2014-01-01

Liver innervation comprises sympathetic, parasympathetic and peptidergic nerve fibers, organized as either afferent or efferent nerves with different origins and roles. Their anatomy and physiology have been studied in the past 30 years, with different results published over time. Hepatocytes are the main cell population of the liver, making up almost 80% of the total liver volume. The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and signaling pathways. In this short review, we have taken the task of condensing the most important data related to how the nervous system interacts with the liver and especially with the hepatocyte population, how it influences their metabolism and functions, and how different receptors and transmitters are involved in this complex process. PMID:24672643

[Physiological basis of a possible increase in the efficacy of the photo- and magnetotherapy of the visual nerve upon partial atrophy and ischemia].

PubMed

Shlygin, V V; Tiuliaev, A P; Ioĭleva, E E; Maksimov, G V

2004-01-01

An approach to the choice of the parameters of physiotherapeutic and biophysical influence on the visual nerve was proposed. The approach is based on parallel photo- and magnetostimulation of excitable fibers in which the morphological and electrophysiological properties of fibers and some parameters of the pathological processes associated with partial artophy and ischemia are taken into account. A method for correlating the photostimulation by light flashes (intensity 65 mWt at emission wavelength 660 nm) of a portion of the retina with the choice of the parameters of magnetic influence (amplitude 73 mT, duration of the wave front of 40 ms, and frequency of pulse sequence of about 1 Hz) on the visual nerve was developed.

Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea.

PubMed

Drescher, M J; Drescher, D G; Khan, K M; Hatfield, J S; Ramakrishnan, N A; Abu-Hamdan, M D; Lemonnier, L A

2006-09-29

Pituitary adenylyl cyclase-activating polypeptide (PACAP), via its specific receptor pituitary adenylyl cyclase-activating polypeptide receptor 1 (PAC1-R), is known to have roles in neuromodulation and neuroprotection associated with glutamatergic and cholinergic neurotransmission, which, respectively, are believed to form the primary basis for afferent and efferent signaling in the organ of Corti. Previously, we identified transcripts for PACAP preprotein and multiple splice variants of its receptor, PAC1-R, in microdissected cochlear subfractions. In the present work, neural localizations of PACAP and PAC1-R within the organ of Corti and spiral ganglion were examined, defining sites of PACAP action. Immunolocalization of PACAP and PAC1-R in the organ of Corti and spiral ganglion was compared with immunolocalization of choline acetyltransferase (ChAT) and synaptophysin as efferent neuronal markers, and glutamate receptor 2/3 (GluR2/3) and neurofilament 200 as afferent neuronal markers, for each of the three cochlear turns. Brightfield microscopy giving morphological detail for individual immunolocalizations was followed by immunofluorescence detection of co-localizations. PACAP was found to be co-localized with ChAT in nerve fibers of the intraganglionic spiral bundle and beneath the inner and outer hair cells within the organ of Corti. Further, evidence was obtained that PACAP is expressed in type I afferent axons leaving the spiral ganglion en route to the auditory nerve, potentially serving as a neuromodulator in axonal terminals. In contrast to the efferent localization of PACAP within the organ of Corti, PAC1-R immunoreactivity was co-localized with afferent dendritic neuronal marker GluR2/3 in nerve fibers passing beneath and lateral to the inner hair cell and in fibers at supranuclear and basal sites on outer hair cells. Given the known association of PACAP with catecholaminergic neurotransmission in sympathoadrenal function, we also re-examined the issue of whether the organ of Corti receives adrenergic innervation. We now demonstrate the existence of nerve fibers within the organ of Corti which are immunoreactive for the adrenergic marker dopamine beta-hydroxylase (DBH). DBH immunoreactivity was particularly prominent in nerve fibers both at the base and near the cuticular plate of outer hair cells of the apical turn, extending to the non-sensory Hensen's cell region. Evidence was obtained for limited co-localization of DBH with PAC1-R and PACAP. In the process of this investigation, we obtained evidence that efferent and afferent nerve fibers, in addition to adrenergic nerve fibers, are present at supranuclear sites on outer hair cells and distributed within the non-sensory epithelium of the apical cochlear turn for rat, based upon immunoreactivity for the corresponding neuronal markers. Overall, PACAP is hypothesized to act within the organ of Corti as an efferent neuromodulator of afferent signaling via PAC1-R that is present on type I afferent dendrites, in position to afford protection from excitotoxicity. Additionally, PACAP/PAC1-R may modulate secretion of catecholamines from adrenergic terminals within the organ of Corti.

Guidance of vascular development: lessons from the nervous system.

PubMed

Larrivée, Bruno; Freitas, Catarina; Suchting, Steven; Brunet, Isabelle; Eichmann, Anne

2009-02-27

The vascular system of vertebrates consists of an organized, branched network of arteries, veins, and capillaries that penetrates all the tissues of the body. One of the most striking features of the vascular system is that its branching pattern is highly stereotyped, with major and secondary branches forming at specific sites and developing highly conserved organ-specific vascular patterns. The factors controlling vascular patterning are not yet completely understood. Recent studies have highlighted the anatomic and structural similarities between blood vessels and nerves. The 2 networks are often aligned, with nerve fibers and blood vessels following parallel routes. Furthermore, both systems require precise control over their guidance and growth. Several molecules with attractive and repulsive properties have been found to modulate the proper guidance of both nerves and blood vessels. These include the Semaphorins, the Slits, and the Netrins and their receptors. In this review, we describe the molecular mechanisms by which blood vessels and axons achieve proper path finding and the molecular cues that are involved in their guidance.

Auditory hair cell innervational patterns in lizards.

PubMed

Miller, M R; Beck, J

1988-05-22

The pattern of afferent and efferent innervation of two to four unidirectional (UHC) and two to nine bidirectional (BHC) hair cells of five different types of lizard auditory papillae was determined by reconstruction of serial TEM sections. The species studies were Crotaphytus wislizeni (iguanid), Podarcis (Lacerta) sicula and P. muralis (lacertids), Ameiva ameiva (teiid), Coleonyx variegatus (gekkonid), and Mabuya multifasciata (scincid). The main object was to determine in which species and in which hair cell types the nerve fibers were innervating only one (exclusive innervation), or two or more hair cells (nonexclusive innervation); how many nerve fibers were supplying each hair cell; how many synapses were made by the innervating fibers; and the total number of synapses on each hair cell. In the species studies, efferent innervation was limited to the UHC, and except for the iguanid, C. wislizeni, it was nonexclusive, each fiber supplying two or more hair cells. Afferent innervation varied both with the species and the hair cell types. In Crotaphytus, both the UHC and the BHC were exclusively innervated. In Podarcis and Ameiva, the UHC were innervated exclusively by some fibers but nonexclusively by others (mixed pattern). In Coleonyx, the UHC were exclusively innervated but the BHC were nonexclusively innervated. In Mabuya, both the UHC and BHC were nonexclusively innervated. The number of afferent nerve fibers and the number of afferent synapses were always larger in the UHC than in the BHC. In Ameiva, Podarcis, and Mabuya, groups of bidirectionally oriented hair cells occur in regions of cytologically distinct UHC, and in Ameiva, unidirectionally oriented hair cells occur in cytologically distinct BHC regions.

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

PubMed Central

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

Sclera

MedlinePlus

... clear front section of the eye) to the optic nerve at the back of the eye. The sclera gives the eyeball its white color. The cornea and sclera are made of the same type of collagen fibers. In the cornea, the fibers are arranged in ...

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

PubMed

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.

Better diagnostic accuracy of neuropathy in obesity: A new challenge for neurologists.

PubMed

Callaghan, Brian C; Xia, Rong; Reynolds, Evan; Banerjee, Mousumi; Burant, Charles; Rothberg, Amy; Pop-Busui, Rodica; Villegas-Umana, Emily; Feldman, Eva L

2018-03-01

To determine the comparative diagnostic characteristics of neuropathy measures in an obese population. We recruited obese participants from the University of Michigan's Weight Management Program. Receiver operative characteristic analysis determined the area under the curve (AUC) of neuropathy measures for distal symmetric polyneuropathy (DSP), small fiber neuropathy (SFN), and cardiovascular autonomic neuropathy (CAN). The best test combinations were determined using stepwise and Score subset selection models. We enrolled 120 obese participants. For DSP, seven of 42 neuropathy measures (Utah Early Neuropathy Score (UENS, N = 62), Michigan Neuropathy Screening Instrument (MNSI) reduced combined index, MNSI examination, nerve fiber density (NFD) leg, tibial F response, MNSI questionnaire, peroneal distal motor latency) had AUCs ≥ 0.75. Three of 19 small fiber nerve measures for SFN (UENS, NFD leg, Sudoscan feet (N = 70)) and zero of 16 CAN measures had AUCs ≥ 0.75. Combinations of tests performed better than individual tests with AUCs of 0.82 for DSP (two parameters) and 0.84 for SFN (three parameters). Many neuropathy measures demonstrate good test performance for DSP in obese participants. Select few small fiber nerve measures performed well for SFN, and none for CAN. Specific combinations of tests should be used for research studies to maximize diagnostic performance in obese cohorts. Published by Elsevier B.V.

Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode.

PubMed

MacEwan, Matthew R; Zellmer, Erik R; Wheeler, Jesse J; Burton, Harold; Moran, Daniel W

2016-01-01

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm 2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation.

Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode

PubMed Central

MacEwan, Matthew R.; Zellmer, Erik R.; Wheeler, Jesse J.; Burton, Harold; Moran, Daniel W.

2016-01-01

Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation. PMID:28008303

Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve regeneration in an axonotmesis rat model.

PubMed

Amado, S; Simões, M J; Armada da Silva, P A S; Luís, A L; Shirosaki, Y; Lopes, M A; Santos, J D; Fregnan, F; Gambarotta, G; Raimondo, S; Fornaro, M; Veloso, A P; Varejão, A S P; Maurício, A C; Geuna, S

2008-11-01

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test hybrid chitosan membranes to use in peripheral nerve reconstruction, either alone or enriched with N1E-115 neural cells. Hybrid chitosan membranes were tested in vitro, to assess their ability in supporting N1E-115 cell survival and differentiation, and in vivo to assess biocompatibility as well as to evaluate their effects on nerve fiber regeneration and functional recovery after a standardized rat sciatic nerve crush injury. Functional recovery was evaluated using the sciatic functional index (SFI), the static sciatic index (SSI), the extensor postural thrust (EPT), the withdrawal reflex latency (WRL) and ankle kinematics. Nerve fiber regeneration was assessed by quantitative stereological analysis and electron microscopy. All chitosan membranes showed good biocompatibility and proved to be a suitable substrate for plating the N1E-115 cellular system. By contrast, in vivo nerve regeneration assessment after crush injury showed that the freeze-dried chitosan type III, without N1E-115 cell addition, was the only type of membrane that significantly improved posttraumatic axonal regrowth and functional recovery. It can be thus suggested that local enwrapping with this type of chitosan membrane may represent an effective approach for the improvement of the clinical outcome in patients receiving peripheral nerve surgery.

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

PubMed

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 fibers, but clarifying the role of sodium channel subtypes in different axonal segments may be useful for the development of novel analgesic strategies. Here, we provide evidence from mice and nonhuman primates that a substantial portion of the C-fiber compound action potential in distal peripheral nerves, but not proximal nerves or dorsal roots, is resistant to tetrodotoxin and that, in mice, this effect is mediated solely by voltage-gated sodium channel 1.8 (Na V 1.8). The functional prominence of Na V 1.8 within the axonal compartment immediately proximal to its termination may affect strategies targeting pain of peripheral origin. Copyright © 2017 the authors 0270-6474/17/375205-11$15.00/0.

Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury

PubMed Central

Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H.; Harper, Matthew M.

2013-01-01

Purpose. To evaluate retina and optic nerve damage following experimental blast injury. Methods. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Results. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Conclusions. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify. PMID:23620426

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

PubMed

Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

2015-12-02

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. Copyright © 2015 the authors 0270-6474/15/3515984-12$15.00/0.

Neural control of the kidney: functionally specific renal sympathetic nerve fibers.

PubMed

DiBona, G F

2000-11-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.

Functionally specific renal sympathetic nerve fibers: role in cardiovascular regulation.

PubMed

DiBona, G F

2001-06-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs through mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers and an innervation that is shared among all the effectors. This arrangement facilitates maximum flexibility in the coordination of the tubules, the blood vessels, and the juxtaglomerular granular cells so as to produce physiologically appropriate responses to a variety of homeostatic requirements.

End-to-side neurotization with the phrenic nerve in restoring the function of toe extension: an experimental study in a rat model.

PubMed

Jia, Xiaotian; Chen, Chao; Yang, Jianyun; Yu, Cong

2018-06-01

The phrenic nerve being transferred to the posterior division of the lower trunk with end-to-end neurorrhaphy is reported to be effective in restoring the function of digit extension in literature. However, the phrenic nerve is extremely important in respiration. We designed an animal experiment to discover whether the phrenic nerve being transferred to the posterior division of the lower trunk with end-to-side neurotization was feasible and provided the theoretical basis. A sum of 36 Sprague-Dawley rats was randomly assigned to one of two groups. In Group A, the phrenic nerve was transferred to the posterior division of the lower trunk with end-to-side neurotization. In Group B, the posterior division of the lower trunk was directly sutured. The results of behavioral assessment, electrophysiology, histology and nerve fiber count and muscle weight at 12 weeks postoperatively were recorded. In Group A, none of the rats experienced tachypnea. The motion of slight toe extension was observed. The results of electrophysiology, histology and nerve fiber count and muscle weight in Group A were not as well as those of Group B, but gradually improved with time. The phrenic nerve being transferred to the posterior division of lower trunk with end-to-side neurotization can partially restore the function of toe extension in a rat model. Whether the function of digit extension can be restored by the phrenic nerve with end-to-side neurotization in humans still needs more practice in clinic.

Primary olfactory projections and the nervus terminalis in the African lungfish: implications for the phylogeny of cranial nerves.

PubMed

von Bartheld, C S; Claas, B; Münz, H; Meyer, D L

1988-08-01

Primary olfactory and central projections of the nervus terminalis were investigated by injections of horseradish peroxidase into the olfactory epithelium in the African lungfish. In addition, gonadotropin-releasing hormone (GnRH) immunoreactivity of the nervus terminalis system was investigated. The primary olfactory projections are restricted to the olfactory bulb located at the rostral pole of the telencephalon; they do not extend into caudal parts of the telencephalon. A vomeronasal nerve and an accessory olfactory bulb could not be identified. The nervus terminalis courses through the dorsomedial telencephalon. Major targets include the nucleus of the anterior commissure and the nucleus praeopticus pars superior. some fibers cross to the contralateral side. A few fibers reach the diencephalon and mesencephalon. No label is present in the "posterior root of the nervus terminalis" (= "Pinkus's nerve" or "nervus praeopticus"). GnRH immunoreactivity is lacking in the "anterior root of the nervus terminalis," whereas it is abundant in nervus praeopticus (Pinkus's nerve). These findings may suggest that the nervus terminalis system originally consisted of two distinct cranial nerves, which have fused-in evolution-in most vertebrates. Theories of cranial nerve phylogeny are discussed in the light of the assumed "binerval origin" of the nervus terminalis system.

The anatomy of the sacrococcygeal cornual region and its clinical relevance.

PubMed

Woon, Jason T K; Stringer, Mark D

2014-09-01

There has been no systematic study of the anatomy of the region between the sacral and coccygeal cornua. Reference texts describe an intercornual ligament connecting these structures. The aim of this study was to investigate the anatomy of this region, which may be relevant to unexplained cases of coccygeal pain (coccydynia) and local nerve blocks. The bony anatomy of the sacrococcygeal (SC) cornual region was analyzed in 33 CT scans obtained from supine adults of mostly European origin with no known SC pathology, 7 μCT scans of cadaver SC specimens, and 105 Asian Indian adult skeletons. A further five cadaver SC specimens were examined histologically. SC cornual fusion was seen in 45% of CT/μCT scans (mean age 67 years, 20 males) and in 20% of adult skeletons (78 males); there was no association with age or sex. In the absence of SC fusion, the mean intersacrococcygeal cornual gap was 7.1 ± 2.4 mm; this was bridged by an intercornual ligament composed of parallel vertical collagen fibers reinforced by elastin fibers on its anterior surface. Small nerve branches were observed adjacent to the ventral aspect of the intercornual ligament and, in one case, traversing the ligament. Ipsilateral sacral and coccygeal cornua are therefore normally bridged by an intercornual ligament that is probably innervated. The cornua are fused on one or both sides in 20-45% of adults. These findings may have implications for some cases of coccydynia and for anesthetists performing local nerve blocks.

Effects of annulus defects and implantation of poly(lactic-co-glycolic acid) (PLGA)/fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular injury disc degeneration.

PubMed

Xin, Long; Xu, Weixing; Yu, Leijun; Fan, Shunwu; Wang, Wei; Yu, Fang; Wang, Zhenbin

2017-05-12

Growth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration (IVD) induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with poly(lactic-co-glycolic acid)/fibrin gel (PLGA) plugs. New Zealand white rabbits (n = 24) received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter; 4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and (d) uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG) content. Nerve ingrowth into the discs was assessed by immunostaining with the nerve marker protein gene product 9.5. Injured discs showed a progressive disc space narrowing with significant disc degeneration and proteoglycan loss, as confirmed by imaging results, molecular and compositional analysis, and histological examinations. In 16G punctured discs, nerve ingrowth was observed on the surface of scar tissue. In annular defects, nerve fibers were found to be distributed along small fissures within the fibrocartilaginous-like tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve fibers were observed growing deeper into the inner AF along the open annular track.  In addition, innervations scores showed significantly higher than those of punctured discs and empty defects. A limited vascular proliferation was found in the injured sites and regenerated tissues. Nerve ingrowth was significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible explanations include (i) annular fissures along the defect and early loss of proteoglycan may facilitate the ingrowth process and (ii) biodegradable PLGA/fibrin gel may promote adverse growth of nerves and blood vessels into deeper parts of injured disc. The rabbit annular defect model of disc degeneration appears suitable to investigate the effects of nerve ingrowth in relation to pain generation.

Quantitative thermal sensory testing -- value of testing for both cold and warm sensation detection in evaluation of small fiber neuropathy.

PubMed

Shukla, Garima; Bhatia, Manvir; Behari, Madhuri

2005-10-01

Small fiber neuropathy is a common neurological disorder, often missed or ignored by physicians, since examination and routine nerve conduction studies are usually normal in this condition. Many methods including quantitative thermal sensory testing are currently being used for early detection of this condition, so as to enable timely investigation and treatment. This study was conducted to assess the yield of quantitative thermal sensory testing in diagnosis of small fiber neuropathy. We included patients presenting with history suggestive of positive and/or negative sensory symptoms, with normal examination findings, clinically suggestive of small fiber neuropathy, with normal or minimally abnormal routine nerve conduction studies. These patients were subjected to quantitative thermal sensory testing using a Medoc TSA-II Neurosensory analyser at two sites and for two modalities. QST data were compared with those in 120 normal healthy controls. Twenty-five patients (16 males, 9 females) with mean age 46.8+/-16.6 years (range: 21-75 years) were included in the study. The mean duration of symptoms was 1.6+/-1.6 years (range: 3 months-6 years). Eighteen patients (72%) had abnormal thresholds in at least one modality. Thermal thresholds were normal in 7 out of the 25 patients. This study demonstrates that quantitative thermal sensory testing is a fairly sensitive method for detection of small fiber neuropathy especially in patients with normal routine nerve conduction studies.

Distribution of TRPV1 and TRPV2 in the human stellate ganglion and spinal cord.

PubMed

Kokubun, Souichi; Sato, Tadasu; Ogawa, Chikara; Kudo, Kai; Goto, Koju; Fujii, Yuki; Shimizu, Yoshinaka; Ichikawa, Hiroyuki

2015-03-17

Immunohistochemistry for the transient receptor potential cation channel subfamily V member 1 (TRPV1) and 2 (TRPV2) was performed on the stellate ganglion and spinal cord in human cadavers. In the stellate ganglion, 25.3% and 16.2% of sympathetic neurons contained TRPV1- and TRPV2-immunoreactivity, respectively. The cell size analysis also demonstrated that proportion of TRPV1- or TRPV2-immunoreactive (-IR) neurons among large (>600 μm(2)) sympathetic neurons (TRPV1, 30.7%; TRPV2, 27.0%) was higher than among small (<600 μm(2)) sympathetic neurons (TRPV1, 22.0%; TRPV2, 13.6%). The present study also demonstrated that 10.0% of sympathetic neurons in the stellate ganglion had pericellular TRPV2-IR nerve fibers. Fourteen percent of large neurons and 7.8% of small neurons were surrounded by TRPV2-IR nerve fibers. TRPV2-immunoreactivity was also detected in about 40% of neuronal cell bodies with pericellular TRPV2-IR nerve fibers. In the lateral horn of the human thoracic spinal cord, TRPV2-immunoreactivity was expressed by some neurons and many varicose fibers surrounding TRPV2-immunonegative neurons. TRPV2-IR pericellular fibers in the stellate ganglion may originate from the lateral horn of the spinal cord. There appears to be TRPV1- or TRPV2-IR sympathetic pathway in the human stellate ganglion and spinal cord. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernandez, Maria G. H.

2010-05-31

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 andmore » 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<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (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).« less

Nerve Regeneration in Conditions of HSV-Infection and an Antiviral Drug Influence.

PubMed

Gumenyuk, Alla; Rybalko, Svetlana; Ryzha, Alona; Savosko, Sergey; Labudzynskyi, Dmytro; Levchuk, Natalia; Chaikovsky, Yuri

2018-05-05

Herpes simplex virus type I (HSV-I) is a latent neuroinfection which can cause focal brain lesion. The role of HSV-infection in nerve regeneration has not been studied so far. The aim of the work was to study sciatic nerve regeneration in the presence of HSV-infection and the influence of an antiviral drug. BALB/c line mice were divided into five groups. Group 1 animals were infected with HSV-I. After resolution of neuroinfection manifestations the sciatic nerve of these animals was crushed. Group 2 mice were administered acyclovir following the same procedures. Groups 3-5 mice served as controls. Thirty days after the operation distal nerve stumps and m.gastrocnemius were studied morphologically and biochemically. Ultrastructural organization of the sciatic nerve in control animals remained intact. Morphometric parameters of the nerves from the experimental groups have not reach control values. However, in the group 1 diameter of nerve fibers was significantly smaller than in the group 2. Both nerve regeneration and m.gastrocnemius reinnervation were confirmed. The muscle hypotrophy was found in groups 1, 2, and 3 (the muscle fibers diameter decreased). Metabolic changes in the muscles of the infected animals (groups 1 and 2) were more pronounced than in control groups 3 and 4. The levels of TBA-active products, conjugated dienes, carbonyl and SH-groups were reduced in m.gastrocnemius of the experimental groups, however no significant difference associated with acyclovir administration was found. HSV-infection is not limited to the local neurodegenerative changes in the CNS but affects regeneration of the injured sciatic nerve. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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 (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (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).

[Structural endpoints for glaucoma studies].

PubMed

Popa-Cherechenau, A; Schmidl, D; Garhöfer, G; Schmetterer, L

2018-03-06

Structural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma. Is the evidence strong enough to establish structural endpoints as surrogate endpoints? Review of current understanding between structure and function in glaucoma. The introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along a circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On a microscopic level there is a strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required. The current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phase 3 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phase 2 and proof of concept studies.

Assessing posterior ocular structures in β-thalassemia minor.

PubMed

Arifoglu, Hasan Basri; Kucuk, Bekir; Duru, Necati; Altunel, Orhan; Gulhan, Ahmet; Ozen, Mustafa; Aygun, Bilal; Atas, Mustafa

2018-02-01

The aim of this study was to investigate the effect of β-thalassemia minor on choroidal, macular, and peripapillary retinal nerve fiber layer thickness. To form the sample, we recruited 40 patients with β-thalassemia minor and 44 healthy participants. We used spectral-domain optical coherence tomography to take all measurements of ocular thickness, as well as measured intraocular pressure, axial length, and central corneal thickness. We later analyzed correlations of hemoglobin levels with ocular parameters. A statistically significant difference emerged between patients with β-thalassemia minor and the healthy controls in terms of mean values of subfoveal, nasal, and temporal choroidal thickness (p = 0.001, p = 0.016, and p = 0.010, respectively). Except for central macular thickness, differences in paracentral macular thicknesses between the groups were also significant (superior: p < 0.001, inferior: p = 0.007, temporal: p = 0.001, and nasal: p = 0.005). Also, no statistically significant differences were noted for retinal nerve fiber layer thickness between two groups. Mean values of subfoveal, nasal, temporal choroidal, and macular thickness for the four quadrants were significantly lower in patients with β-thalassemia minor than in healthy controls.

Automated retinal nerve fiber layer defect detection using fundus imaging in glaucoma.

PubMed

Panda, Rashmi; Puhan, N B; Rao, Aparna; Padhy, Debananda; Panda, Ganapati

2018-06-01

Retinal nerve fiber layer defect (RNFLD) provides an early objective evidence of structural changes in glaucoma. RNFLD detection is currently carried out using imaging modalities like OCT and GDx which are expensive for routine practice. In this regard, we propose a novel automatic method for RNFLD detection and angular width quantification using cost effective redfree fundus images to be practically useful for computer-assisted glaucoma risk assessment. After blood vessel inpainting and CLAHE based contrast enhancement, the initial boundary pixels are identified by local minima analysis of the 1-D intensity profiles on concentric circles. The true boundary pixels are classified using random forest trained by newly proposed cumulative zero count local binary pattern (CZC-LBP) and directional differential energy (DDE) along with Shannon, Tsallis entropy and intensity features. Finally, the RNFLD angular width is obtained by random sample consensus (RANSAC) line fitting on the detected set of boundary pixels. The proposed method is found to achieve high RNFLD detection performance on a newly created dataset with sensitivity (SN) of 0.7821 at 0.2727 false positives per image (FPI) and the area under curve (AUC) value is obtained as 0.8733. Copyright © 2018 Elsevier Ltd. All rights reserved.

[From Descartes to fMRI. Pain theories and pain concepts].

PubMed

Handwerker, H O

2007-08-01

In the seventeenth century the philosopher Rene Descartes was the forerunner by establishing a scientific hypothesis on the origin of pain. Much later, in the nineteenth century, pain hypotheses emerged which explained the pain sensation either on the basis of intense stimulation of any kind of nerve fibers (intensity hypothesis) or on the basis of specific nociceptors (specificity hypothesis). The "gate control theory" established by Melzack and Wall (1964) offered an explanation of modulations of pain sensation by the interaction between nociceptive and non-nociceptive nerve fibers and by descending control in the central nervous system. Though this hypothesis is outdated in its original form, it had - in a more common formulation - a great influence on our understanding of pain. For building a bridge to our present knowledge, the molecular structure of the nociceptor membrane is of particular importance. On this basis also new pain therapies have been developed. On the other hand, the methods of functional imaging allow the identification of brain regions related to pain processing at a macroscopic level. This new technology opened up new ways of understanding chronic pain processes and new possibilities for the control of therapeutic effects.

[Allergic inflammation in respiratory system].

PubMed

An, Lifeng; Wang, Yanshu; Li, Lin

2015-02-01

The pathophysiology of allergic disease such as asthma and allergic rhinitis tell the similar story: when the endogenous and exogenous inflammatory mechanisms occur disorder, the body may begin with inflammatory cell activation, namely through the release of cytokine and inflammatory mediator role in the corresponding target cells, activate the sensory nerve fiber, acting on the cell organ specificity effect, clinical symptoms. This article is divided into the following five parts focused on the research progress of allergic inflammatory diseases: (1) inflammatory cells; (2) staphylococcus aureus superantigen; (3) small molecules (cytokines, inflammatory mediators, lipid classes medium); (4) nerve fibers and effect cells; (5) genetic and epigenetic factors.

A Nerve Growth Factor Peptide Retards Seizure Development and Inhibits Neuronal Sprouting in a Rat Model of Epilepsy

NASA Astrophysics Data System (ADS)

Rashid, Kashif; van der Zee, Catharina E. E. M.; Ross, Gregory M.; Chapman, C. Andrew; Stanisz, Jolanta; Riopelle, Richard J.; Racine, Ronald J.; Fahnestock, Margaret

1995-10-01

Kindling, an animal model of epilepsy wherein seizures are induced by subcortical electrical stimulation, results in the upregulation of neurotrophin mRNA and protein in the adult rat forebrain and causes mossy fiber sprouting in the hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve growth factor domain that interferes with the binding of neurotrophins to their receptors resulted in significant retardation of kindling and inhibition of mossy fiber sprouting. These findings suggest a critical role for neurotrophins in both kindling and kindling-induced synaptic reorganization.

The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin.

PubMed

McVey Neufeld, K A; Perez-Burgos, A; Mao, Y K; Bienenstock, J; Kunze, W A

2015-05-01

The microbiome is essential for normal myenteric intrinsic primary afferent neuron (IPAN) excitability. These neurons control gut motility and modulate gut-brain signaling by exciting extrinsic afferent fibers innervating the enteric nervous system via an IPAN to extrinsic fiber sensory synapse. We investigated effects of germ-free (GF) status and conventionalization on extrinsic sensory fiber discharge in the mesenteric nerve bundle and IPAN electrophysiology, and compared these findings with those from specific pathogen-free (SPF) mice. As we have previously shown that the IPAN calcium-dependent slow afterhyperpolarization (sAHP) is enhanced in GF mice, we also examined the expression of the calcium-binding protein calbindin in these neurons in these different animal groups. IPAN sAHP and mesenteric nerve multiunit discharge were recorded using ex vivo jejunal gut segments from SPF, GF, or conventionalized (CONV) mice. IPANs were excited by adding 5 μM TRAM-34 to the serosal superfusate. We probed for calbindin expression using immunohistochemical techniques. SPF mice had a 21% increase in mesenteric nerve multiunit firing rate and CONV mice a 41% increase when IPANs were excited by TRAM-34. For GF mice, this increase was barely detectable (2%). TRAM-34 changed sAHP area under the curve by -77 for SPF, +3 for GF, or -54% for CONV animals. Calbindin-immunopositive neurons per myenteric ganglion were 36% in SPF, 24% in GF, and 52% in CONV animals. The intact microbiome is essential for normal intrinsic and extrinsic nerve function and gut-brain signaling. © 2015 John Wiley & Sons Ltd.

Aging Induces Changes in the Somatic Nerve and Postsynaptic Component without Any Alterations in Skeletal Muscles Morphology and Capacity to Carry Load of Wistar Rats

PubMed Central

Krause Neto, Walter; Silva, Wellington de Assis; Ciena, Adriano P.; de Souza, Romeu R.; Anaruma, Carlos A.; Gama, Eliane F.

2017-01-01

The present study aimed to analyze the morphology of the peripheral nerve, postsynaptic compartment, skeletal muscles and weight-bearing capacity of Wistar rats at specific ages. Twenty rats were divided into groups: 10 months-old (ADULT) and 24 months-old (OLD). After euthanasia, we prepared and analyzed the tibial nerve using transmission electron microscopy and the soleus and plantaris muscles for cytofluorescence and histochemistry. For the comparison of the results between groups we used dependent and independent Student's t-test with level of significance set at p ≤ 0.05. For the tibial nerve, the OLD group presented the following alterations compared to the ADULT group: larger area and diameter of both myelinated fibers and axons, smaller area occupied by myelinated and unmyelinated axons, lower numerical density of myelinated fibers, and fewer myelinated fibers with normal morphology. Both aged soleus and plantaris end-plate showed greater total perimeter, stained perimeter, total area and stained area compared to ADULT group (p < 0.05). Yet, aged soleus end-plate presented greater dispersion than ADULT samples (p < 0.05). For the morphology of soleus and plantaris muscles, density of the interstitial volume was greater in the OLD group (p < 0.05). No statistical difference was found between groups in the weight-bearing tests. The results of the present study demonstrated that the aging process induces changes in the peripheral nerve and postsynaptic compartment without any change in skeletal muscles and ability to carry load in Wistar rats. PMID:29326543

Histopathological features of a patient with Charcot-Marie-Tooth disease type 2U/AD-CMTax-MARS.

PubMed

Hirano, Makito; Oka, Nobuyuki; Hashiguchi, Akihiro; Ueno, Shuichi; Sakamoto, Hikaru; Takashima, Hiroshi; Higuchi, Yujiro; Kusunoki, Susumu; Nakamura, Yusaku

2016-12-01

Charcot-Marie-Tooth (CMT) disease is a complex of peripheral nervous system disorders. CMT type 2U (CMT2U) is an autosomal dominant (AD) disease caused by mutations in the MARS gene encoding methionyl-tRNA synthetase; this disease has thus been newly called AD-CMTax-MARS. A few families with mutations in the MARS gene have been reported, without detailed histopathological findings. We describe a 70-year-old woman who had bilateral dysesthesia of the soles since the age of 66 years. Sural nerve biopsy showed a decrease in the density of large myelinated nerve fibers. Increased clusters of regenerating myelinated nerve fibers were noted. Electron microscopic analyses revealed degeneration of unmyelinated nerves. There was no vasculitis or inflammatory cell infiltration. Genetic analysis identified a heterozygous p.P800T mutation, a reported mutation in the MARS gene. We report the detailed histopathological findings in a patient with CMT2U/AD-CMTax-MARS. The findings are similar to those found in CMT2D caused by mutations in the GARS gene, encoding glycyl-tRNA synthetase. © 2016 Peripheral Nerve Society.

Comparative ultrastructure of vallate, foliate and fungiform taste buds of golden Syrian hamster.

PubMed

Miller, R L; Chaudhry, A P

1976-01-01

A fine-structure study of the hamster fungiform, foliate and vallate taste buds was undertaken for comparative purposes. All three taste bud types shared in common composition of the dark cells, light cells, basal cells, nerve fibers and nerve endings and undifferentiated peripheral cells, but morphological difference existed among them. The foliate and vallate taste buds were quite similar in their ultrastructural morphology. Their dark cells displayed long apical necks, long apical microvilli, apical osmiophilic secretory granules and an abundant rough endoplasmic reticulum. The dark cells of the fungiform taste buds, however, showed no neck formation and lacked apical osmiophilic granules. They had short apical microvilli and relatively scant rough endoplasmic reticulum. There was no difference in the fine structure features of the light cells, basal cells and neural elements of different types of taste buds. Both light and dark cells were much more readily distinguishable in foliate and vallate buds than in fungiform buds at both light-and electron-microscopic levels. Foliate and vallate buds demonstrated homogeneous dense substance within the taste pores while fungiform pores were frequently empty. It is speculated that the differences in taste bud morphology may be due to their different lingual locations and/or may be a reflection of the differences in the inductive influences from different nerves. Furthermore, structural differences may be responsible for varying thresholds to different taste modalities.