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.

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

NASA Technical Reports Server (NTRS)

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

1991-01-01

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

UNMYELINATED FIBERS OF THE ANTERIOR ETHMOIDAL NERVE IN THE RAT CO-LOCALIZE WITH NEURONS IN THE MEDULLARY DORSAL HORN AND VENTROLATERAL MEDULLA ACTIVATED BY NASAL STIMULATION

PubMed Central

Hollandsworth, Michael P.; DiNovo, Karyn M.; McCulloch, Paul F.

2009-01-01

The anterior ethmoidal nerve (AEN) innervates the nasal passages and external nares, and serves as the afferent limb of the nasopharyngeal and diving responses. However, although 65% of the AEN is composed of unmyelinated fibers, it has not been determined whether this afferent signal is carried by unmyelinated or myelinated fibers. We used the transganglionic tracers WGA-HRP, IB4-HRP, and CTB-HRP to trace the central projections of the AEN of the rat. Interpretation of the labeling patterns suggests that AEN unmyelinated fibers project primarily to the ventral tip of the ipsilateral medullary dorsal horn (MDH) at the level of the area postrema. Other unmyelinated projections were to the ventral paratrigeminal nucleus and ventrolateral medulla, specifically the Bötzinger and RVLM/C1 regions. Myelinated AEN fibers projected to the ventral paratrigeminal and mesencephalic trigeminal nuclei. Stimulating the nasal passages of urethane-anesthetized rats with ammonia vapors produced the nasopharyngeal response that included apnea, bradycardia and an increase in arterial blood pressure. Central projections of the AEN co-localized with neurons within both MDH and RVLM/C1 that were activated by nasal stimulation. Within the ventral MDH the density of AEN terminal projections positively correlated with the rostral-caudal location of activated neurons, especially at and just caudal to the obex. We conclude that unmyelinated AEN terminal projections are involved in the activation of neurons in the MDH and ventrolateral medulla that participate in the nasopharyngeal response in the rat. We also found that IB4-HRP was a much less robust tracer than WGA-HRP. PMID:19732757

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.

Allodynia mediated by C-tactile afferents in human hairy skin.

PubMed

Nagi, Saad S; Rubin, Troy K; Chelvanayagam, David K; Macefield, Vaughan G; Mahns, David A

2011-08-15

We recently showed a contribution of low-threshold cutaneous mechanoreceptors to vibration-evoked changes in the perception of muscle pain. Neutral-touch stimulation (vibration) of the hairy skin during underlying muscle pain evoked an overall increase in pain intensity, i.e. allodynia. This effect appeared to be dependent upon cutaneous afferents, as allodynia was abolished by intradermal anaesthesia. However, it remains unclear whether allodynia results from activation of a single class of cutaneous afferents or the convergence of inputs from multiple classes. Intriguingly, no existing human study has examined the contribution of C-tactile (CT) afferents to allodynia. Detailed psychophysical observations were made in 29 healthy subjects (18 males and 11 females). Sustained muscle pain was induced by infusing hypertonic saline (HS: 5%) into tibialis anterior muscle (TA). Sinusoidal vibration (200 Hz–200 μm) was applied to the hairy skin overlying TA. Pain ratings were recorded using a visual analogue scale (VAS). In order to evaluate the role of myelinated and unmyelinated cutaneous afferents in the expression of vibration-evoked allodynia, compression block of the sciatic nerve, and low-dose intradermal anaesthesia (Xylocaine 0.25%) were used, respectively. In addition, the modulation of muscle pain by gentle brushing (1.0 and 3.0 cm s(−1))--known to excite CT fibres--was examined. Brushing stimuli were applied to the hairy skin with all fibres intact and following the blockade of myelinated afferents. During tonic muscle pain (VAS 4–6), vibration evoked a significant and reproducible increase in muscle pain (allodynia) that persisted following compression of myelinated afferents. During compression block, the sense of vibration was abolished, but the vibration-evoked allodynia persisted. In contrast, selective anaesthesia of unmyelinated cutaneous afferents abolished the allodynia, whereas the percept of vibration remained unaffected. Furthermore, allodynia was preserved in the adjacent non-anaesthetized skin. Conformingly, gentle brushing produced allodynia (at both brushing speeds) that persisted during the blockade of myelinated afferents. Prior to the induction and following cessation of muscle pain, all subjects reported vibration and brushing as non-painful (VAS = 0). These results demonstrate that CT fibres in hairy skin mediate allodynia, and that CT-mediated inputs have a pluripotent central effect.

Auditory-nerve single-neuron thresholds to electrical stimulation from scala tympani electrodes.

PubMed

Parkins, C W; Colombo, J

1987-12-31

Single auditory-nerve neuron thresholds were studied in sensory-deafened squirrel monkeys to determine the effects of electrical stimulus shape and frequency on single-neuron thresholds. Frequency was separated into its components, pulse width and pulse rate, which were analyzed separately. Square and sinusoidal pulse shapes were compared. There were no or questionably significant threshold differences in charge per phase between sinusoidal and square pulses of the same pulse width. There was a small (less than 0.5 dB) but significant threshold advantage for 200 microseconds/phase pulses delivered at low pulse rates (156 pps) compared to higher pulse rates (625 pps and 2500 pps). Pulse width was demonstrated to be the prime determinant of single-neuron threshold, resulting in strength-duration curves similar to other mammalian myelinated neurons, but with longer chronaxies. The most efficient electrical stimulus pulse width to use for cochlear implant stimulation was determined to be 100 microseconds/phase. This pulse width delivers the lowest charge/phase at threshold. The single-neuron strength-duration curves were compared to strength-duration curves of a computer model based on the specific anatomy of auditory-nerve neurons. The membrane capacitance and resulting chronaxie of the model can be varied by altering the length of the unmyelinated termination of the neuron, representing the unmyelinated portion of the neuron between the habenula perforata and the hair cell. This unmyelinated segment of the auditory-nerve neuron may be subject to aminoglycoside damage. Simulating a 10 micron unmyelinated termination for this model neuron produces a strength-duration curve that closely fits the single-neuron data obtained from aminoglycoside deafened animals. Both the model and the single-neuron strength-duration curves differ significantly from behavioral threshold data obtained from monkeys and humans with cochlear implants. This discrepancy can best be explained by the involvement of higher level neurologic processes in the behavioral responses. These findings suggest that the basic principles of neural membrane function must be considered in developing or analyzing electrical stimulation strategies for cochlear prostheses if the appropriate stimulation of frequency specific populations of auditory-nerve neurons is the objective.

Effect of high doses of 2-CdA on Schwann cells of mouse peripheral nerve.

PubMed

Djaldetti, R; Hart, J; Alexandrova, S; Cohen, S; Beilin, B; Djaldetti, M; Bessler, H

1996-07-01

The present study was undertaken to examine the effect of 2-CdA (Leustatin) on the Schwann cells of myelinated and unmyelinated fibers of peripheral mouse nerve. Two groups of mice were injected intravenously for seven days with 2-CdA: one group received daily doses of 1 mg/kg and the other 0.5 mg/kg. Both doses exceeded those accepted in clinical practice. Mice injected with saline served as controls. The sciatic nerve was then dissected and examined with a transmission electron microscope. The Schwann cells of both the myelinated and unmyelinated nerve fibers of the animals receiving the higher doses of 2-CdA showed nuclear and nucleolus damage, loss of heterochromatin, vacuolization and disorganization of the myelin sheaths. The mesaxons and the axons were also damaged. The Schwann cells of the animals treated with the lower doses appeared undamaged. The results indicate that in contrast to other anticancer drugs known to produce peripheral neuropathy, 2-CdA may cause damage to the Schwann cells only at doses exceeding the therapeutic ones.

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.

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

Axonal degeneration and regeneration in sensory roots in a genital herpes model.

PubMed

Soffer, D; Martin, J R

1989-01-01

In a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, roots of the lower spinal cord were examined 5 days to 6 months after inoculation. Using immunoperoxidase methods on paraffin sections, viral antigen was found in sensory ganglia, their proximal roots and distal nerves on days 5 and 6 after infection. In Epon sections, most mice had focal sensory root abnormalities in lower thoracic, lumbar or sacral levels. At days 7 and 10, lesions showed chiefly nerve fiber degeneration, particularly of large myelinated fibers. At 2 weeks, lesions contained relatively large bundles of small unmyelinated fibers with immature axon-Schwann cell relationships. From 3 to 6 weeks, lesions again contained many more small unmyelinated fibers than normal but, in increasing proportions, axons in bundles were isolated from their neighbors by Schwann cell cytoplasm, and Schwann cells having 1:1 relationships with axons showed mesaxon or thin myelin sheath formation. At later times, the proportion of small unmyelinated axons decreased in parallel with increased numbers of small myelinated axons. By 6 months, affected roots showed a relative reduction in large myelinated fibers, increased proportions of small myelinated fibers and Schwann cell nuclei. Numbers of unmyelinated fibers were reduced relative to 3- to 6-week lesions. Axonal degeneration and regeneration appears to be the chief pathological change in sensory roots in this model. If regenerated fibers arise from latently infected neurons, then establishment of latency is not a relatively silent event, but is associated with major long-lasting, morphologically detectable effects.

N-cadherin expression in palisade nerve endings of rat vellus hairs.

PubMed

Kaidoh, Toshiyuki; Inoué, Takao

2008-02-01

Palisade nerve endings (PNs) are mechanoreceptors around vellus hairs of mammals. Each lanceolate nerve ending (LN) of the PN is characterized by a sensory nerve ending symmetrically sandwiched by two processes of type II terminal Schwann cells (tSCIIs). However, the molecular mechanisms underlying the structural organization of the PN are poorly understood. Electron microscopy showed that adherens junctions appeared to adhere to the sensory nerve ending and tSCII processes, so we examined the location of the N-cadherin adhesion system in PNs of rat vellus hairs by using immunoelectron microscopy. N-cadherin localized near both ends of the cell boundary between sensory nerve ending and tSCII processes, which corresponded to the sites of adherens junctions. We further found cadherin-associated proteins, alpha- and beta-catenins, at the linings of adherens junctions. Three-dimensional reconstruction of immunoelectron microscopic serial thin sections showed four linear arrays of N-cadherin arranged longitudinally along the LN beneath the four longitudinal borders of two tSCII processes. In contrast, sensory nerve fibers just proximal to the LNs formed common unmyelinated nerve fibers, in which N-cadherin was located mainly at the mesaxon of type I terminal Schwann cells (tSCIs). These results suggest that the four linear arrays of N-cadherin-mediated junctions adhere the sensory nerve ending and tSCII processes side by side to form the characteristic structure of the LN, and the structural differences between the LNs and the proximal unmyelinated nerve fibers possibly are due to the difference in the pattern of N-cadherin expression between sensory nerve endings and tSCII or tSCI processes. (c) 2007 Wiley-Liss, Inc.

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.

Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit

PubMed Central

Allmeling, Christina; Jokuszies, Andreas; Reimers, Kerstin; Kall, Susanne; Vogt, Peter M

2006-01-01

Defects of peripheral nerves still represent a challenge for surgical nerve reconstruction. Recent studies concentrated on replacement by artificial nerve conduits from different synthetic or biological materials. In our study, we describe for the first time the use of spider silk fibres as a new material in nerve tissue engineering. Schwann cells (SC) were cultivated on spider silk fibres. Cells adhered quickly on the fibres compared to polydioxanone monofilaments (PDS). SC survival and proliferation was normal in Live/Dead assays. The silk fibres were ensheathed completely with cells. We developed composite nerve grafts of acellularized veins, spider silk fibres and SC diluted in matrigel. These artificial nerve grafts could be cultivated in vitro for one week. Histological analysis showed that the cells were vital and formed distinct columns along the silk fibres. In conclusion, our results show that artificial nerve grafts can be constructed successfully from spider silk, acellularized veins and SC mixed with matrigel. PMID:16989736

Comparative study of the retinal nerve fibre layer thickness performed with optical coherence tomography and GDx scanning laser polarimetry in patients with primary open-angle glaucoma.

PubMed

Wasyluk, Jaromir T; Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona

2012-03-01

We compared the parameters of retinal nerve fibre layer in patients with advanced glaucoma with the use of different OCT (Optical Coherence Tomograph) devices in relation to analogical measurements performed with GDx VCC (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser polarimetry. Study subjects had advanced primary open-angle glaucoma, previously treated conservatively, diagnosed and confirmed by additional examinations (visual field, ophthalmoscopy of optic nerve, gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18-70 years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined. 1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2) performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3) measuring the retinal nerve fibre layer thickness with 3 different optical coherence tomographs. The parameters of the retinal nerve fibre layer thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000 devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer thickness in the upper sector, and correlation of NFI (GDx) with mean retinal nerve fibre layer thickness in OCT examinations. Absolute values of the retinal nerve fibre layer thickness (measured in µm) differ significantly between GDx and all OCT devices. Examination with OCT devices is a sensitive diagnostic method of glaucoma, with good correlation with the results of GDx scanning laser polarimetry of the patients.

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

A light and transmission electron microscope study of the distribution and ultrastructural features of peripheral nerve processes in the extra-retinal layers of the zebrafish eye.

PubMed

Chapman, G B; Tarboush, R; Eagles, D A; Connaughton, V P

2009-08-01

The distribution and ultrastructural features of peripheral nerve processes in the extra-retinal layers of the eyes of the zebrafish, Danio rerio (Hamilton), were investigated using light and transmission electron microscopy. A comparative study of the quality of preservation provided by three different fixation procedures revealed no consistently striking general differences. However, somewhat subjectively, the fixative containing Millonig's buffer did consistently provide better fixation of myelin. Overall, nerve processes, depending on the site studied, were distributed as either (1) bundles (in the choroid near the optic nerve head and in the choroid adjacent to the limbus), (2) linear arrays (in the junction between the sclera and cartilage and in the choroid adjacent to the retina) or (3) individual units (in the choroid under the cartilage or in the sclera). Both myelinated and unmyelinated processes were identified in these locations. Myelinated processes usually contained both neurofilaments and neurotubules, but a few apparently contained only neurofilaments. Unmyelinated processes usually contained mainly neurotubules, but a few apparently contained only neurofilaments. Taken together, these findings indicate innervation of extra-retinal structures, as seen in zebrafish, is highly conserved among vertebrates, further supporting the use of zebrafish as a model for the vertebrate visual system.

Nerve fibres are required to evoke a contact sensitivity response in mice

PubMed Central

Beresford, Lorna; Orange, Oliver; Bell, Eric B; Miyan, Jaleel A

2004-01-01

Previous work has indicated that the dermis and epidermis of skin contains abundant nerve fibres closely associated with Langerhans' cells. We have investigated whether these nerve endings are necessary for inducing and evoking a contact sensitivity (CS) response. Topical application of a general or a peptide (calcitonin gene-related peptide and substance P)-specific neurotoxin was employed to destroy the nerve fibres at skin sites subsequently used to induce or evoke the CS response. Elimination of nerve fibres abolished both induction and effector stages of the specific CS response. Denervation did not destroy the local Langerhans' cells, which were observed in increased numbers, or prevent them from migrating to lymph nodes. The local CS response was also abolished by systemic deletion of capsaicin-sensitive nerve fibres, suggesting that the loss of response was not non-specific but associated with the loss of specific nerve fibres. The results indicate that peptidergic nerve fibres are required to elicit a CS response and may be vital to the normal function of the immune system. PMID:14678206

Comparative study of the retinal nerve fibre layer thickness performed with optical coherence tomography and GDx scanning laser polarimetry in patients with primary open-angle glaucoma

PubMed Central

Wasyluk, Jaromir T.; Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona

2012-01-01

Summary Background We compared the parameters of retinal nerve fibre layer in patients with advanced glaucoma with the use of different OCT (Optical Coherence Tomograph) devices in relation to analogical measurements performed with GDx VCC (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser polarimetry. Material/Methods Study subjects had advanced primary open-angle glaucoma, previously treated conservatively, diagnosed and confirmed by additional examinations (visual field, ophthalmoscopy of optic nerve, gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18–70 years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined. 1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2) performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3) measuring the retinal nerve fibre layer thickness with 3 different optical coherence tomographs. Results The parameters of the retinal nerve fibre layer thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000 devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer thickness in the upper sector, and correlation of NFI (GDx) with mean retinal nerve fibre layer thickness in OCT examinations. Absolute values of the retinal nerve fibre layer thickness (measured in μm) differ significantly between GDx and all OCT devices. Conclusions Examination with OCT devices is a sensitive diagnostic method of glaucoma, with good correlation with the results of GDx scanning laser polarimetry of the patients. PMID:22367131

Axonal loss from acute optic neuropathy documented by scanning laser polarimetry

PubMed Central

Meier, F M; Bernasconi, P; Stürmer, J; Caubergh, M-J; Landau, K

2002-01-01

Background/aims: Retinal nerve fibre layer analysis by scanning laser polarimetry has been shown to facilitate diagnosis of glaucoma while its role in glaucoma follow up is still unclear. A major difficulty is the slow reduction of retinal nerve fibre layer thickness in glaucomatous optic neuropathy. Eyes of patients were studied after acute retrobulbar optic nerve lesion in order to evaluate the usefulness of scanning laser polarimetry in documenting retinal nerve fibre layer loss over time. Methods: Five patients who suffered severe retrobulbar optic neuropathy have had repeated measurements of the retinal nerve fibre layer using scanning laser polarimetry at various intervals, the first examination being within 1 week of injury. Results: All eyes showed a marked decrease in peripapillary retinal nerve fibre layer thickness, which followed an exponential curve and occurred predominantly within 8 weeks of injury. Compared to a previous study using red-free photographs, scanning laser polarimetry showed retinal nerve fibre layer loss earlier in the course of descending atrophy. Conclusion: Scanning laser polarimetry is useful for early detection and documentation of retinal nerve fibre layer loss following acute injury to the retrobulbar optic nerve. It seems to be a promising tool for follow up of individual glaucoma patients. PMID:11864884

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

Are endometrial nerve fibres unique to endometriosis? A prospective case-control study of endometrial biopsy as a diagnostic test for endometriosis in women with pelvic pain.

PubMed

Ellett, Lenore; Readman, Emma; Newman, Marsali; McIlwaine, Kate; Villegas, Rocio; Jagasia, Nisha; Maher, Peter

2015-12-01

Can the presence of endometrial nerve fibres be used as a diagnostic test for endometriosis in women with pelvic pain? Endometrial fine nerve fibres were seen in the endometrium of women both with and without endometriosis, making their detection a poor diagnostic tool for endometriosis. Laparoscopy and biopsy are currently the gold standard for making a diagnosis of endometriosis. It has been reported that small density nerve fibres in the functional layer of the endometrium are unique to women with endometriosis and hence nerve fibre detection could function as a less invasive diagnostic test of endometriosis. However, it may be that other painful conditions of the pelvis are also associated with these nerve fibres. We therefore focused this prospective study on women with pelvic pain to examine the efficacy of endometrial nerve fibre detection as a diagnostic test for endometriosis. This prospective case-control study conducted between July 2009 and July 2013 included 44 women with pelvic pain undergoing laparoscopic examination for the diagnosis of endometriosis. Immunohistochemical nerve fibre detection in endometrial curettings and biopsies using anti-protein gene product 9.5 was compared with surgical diagnosis. Paired endometrial biopsies and curettings were taken from patients with (n = 22, study group) and without (n = 22, control group) endometriosis. Tissue was analysed by immunohistochemistry and nerve fibres were counted whenever they were present in the functional layer of the endometrium. Fine nerve fibres were present in the eutopic endometrium of patients both with and without endometriosis. The presence of nerve fibres in curettings was not effective for either diagnosing or excluding endometriosis; sensitivity and specificity were 31.8 and 45.5% respectively, positive predictive value was 36.8% and negative predictive value was 40.0%. Few endometrial biopsy specimens were found to have nerve fibres present; sensitivity and specificity for endometrial biopsy were 13.6 and 68.2% respectively, positive predictive value was 30.0% and negative predictive value was 44.1%. This was a relatively small sample size and studies like this are subject to the heterogeneous nature of the patient population and tissue samples, despite our best efforts to regulate these parameters. Our results demonstrate that fine nerve fibres are present in women with and without endometriosis. Future work should focus on the function of endometrial nerves and whether these nerves are involved with the subfertility or pain that endometriosis sufferers experience. Our study does not support the detection of endometrial nerve fibres as a non-invasive diagnostic test of endometriosis in women with pelvic pain. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The sensory-motor bridge neurorraphy: an anatomic study of feasibility between sensory branch of the musculocutaneous nerve and deep branch of the radial nerve.

PubMed

Goubier, Jean-Noel; Teboul, Frédéric

2011-05-01

Restoring elbow flexion remains the first step in the management of total palsy of the brachial plexus. Non avulsed upper roots may be grafted on the musculocutaneous nerve. When this nerve is entirely grafted, some motor fibres regenerate within the sensory fibres quota. Aiming potential utilization of these lost motor fibres, we attempted suturing the sensory branch of the musculocutaneous nerve onto the deep branch of the radial nerve. The objective of our study was to assess the anatomic feasibility of such direct suturing of the terminal sensory branch of the musculocutaneous nerve onto the deep branch of the radial nerve. The study was carried out with 10 upper limbs from fresh cadavers. The sensory branch of the musculocutaneous muscle was dissected right to its division. The motor branch of the radial nerve was identified and dissected as proximally as possible into the radial nerve. Then, the distance separating the two nerves was measured so as to assess whether direct neurorraphy of the two branches was feasible. The excessive distance between the two branches averaged 6 mm (1-13 mm). Thus, direct neurorraphy of the sensory branch of the musculocutaneous nerve and the deep branch of the radial nerve was possible. When the whole musculocutaneous nerve is grafted, some of its motor fibres are lost amongst the sensory fibres (cutaneous lateral antebrachial nerve). By suturing this sensory branch onto the deep branch of the radial nerve, "lost" fibres may be retrieved, resulting in restoration of digital extension. Copyright © 2011 Wiley-Liss, Inc.

Adrenergic nerve fibres and mast cells: correlation in rat thymus.

PubMed

Artico, Marco; Cavallotti, Carlo; Cavallotti, Daniela

2002-10-21

The interactions between adrenergic nerve fibres and mast cells (MCs) were studied in the thymus of adult and old rats by morphological methods and by quantitative analysis of images (QAIs). The whole thymus was drawn in adult (12 months old) rats: normal, sympathectomized or electrostimulated. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for detection of microanatomical details and with Bodian's method for identification of the whole nerve fibres. Thymic MCs were stained with Astrablau. Histofluorescence microscopy was used for staining of adrenergic nerve fibres. Finally, all morphological results were submitted to the QAIs and statistical analysis of data. Our results suggest that after surgical sympathectomy, the greater part of adrenergic nerve fibres disappear while related MCs appear to show less evident fluorescence and few granules. On the contrary, electrostimulation of the cervical superior ganglion induced an increase in the fluorescence of adrenergic nerve fibres and of related MCs.

SFN-SIQ, SFNSL and skin biopsy of 55 cases with small fibre involvement.

PubMed

Sun, Bo; Li, Yifan; Liu, Lizhi; Chen, Zhaohui; Ling, Li; Yang, Fei; Liu, Jiexiao; Liu, Hong; Huang, Xusheng

2018-05-01

Purpose/aim of the study: To date, there are no validated screening scales for small fibre neuropathy. This study investigated the small-fibre neuropathy and the symptom inventory questionnaire as well as the small fibre neuropathy screening list for small fibre neuropathy diagnosis. Fifty-five patients were divided into small fibre neuropathy and mixed fibre damage groups. Relevant scales, nerve conduction studies and skin biopsies were performed. Relationships between the intraepidermal nerve fibre density and different scales as well as the diagnostic and cut-off values (score at which Youden's index is largest) were determined. Compared with healthy Chinese participants, 20 patients were diagnosed with small fibre neuropathy. Intraepidermal nerve fibre density was moderately and highly correlated with the small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list, respectively. The diagnostic values were moderate and high for the small fibre neuropathy-symptom inventory questionnaire (cut-off value = 5, sensitivity = 80%, specificity = 81.8%) and small fibre neuropathy screening list (cut-off value = 8, sensitivity = 94.1%, specificity = 90.9%), respectively. There were no significant differences in the visual analogue scale between the small fibre neuropathy group, mixed small and large fibre neuropathy group, pure large fibre neuropathy group and the normal group. Small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list represent potential small fibre neuropathy screening tools. Abbreviations EMG electromyography ENA anti-extractable nuclear antigens ESR erythrocyte sedimentation rate IENFD intraepidermal nerve fibre density IGT impaired glucose tolerance NCS nerve conduction studies NDS neuropathy disability score OGTT oral glucose tolerance test PGP protein gene product PN peripheral neuropathy ROC receiver operating characteristic curve ROC-AUC area under the ROC curve SFN small fibre neuropathy SFN-SIQ small-fibre neuropathy and symptom inventory questionnaire SFNSL small fibre neuropathy screening list VAS visual analogue scale WHO World Health Organization.

Microscopic anatomy of the visceral fasciae.

PubMed

Stecco, Carla; Sfriso, Maria Martina; Porzionato, Andrea; Rambaldo, Anna; Albertin, Giovanna; Macchi, Veronica; De Caro, Raffaele

2017-07-01

The term 'visceral fascia' is a general term used to describe the fascia lying immediately beneath the mesothelium of the serosa, together with that immediately surrounding the viscera, but there are many types of visceral fasciae. The aim of this paper was to identify the features they have in common and their specialisations. The visceral fascia of the abdomen (corresponding to the connective tissue lying immediately beneath the mesothelium of the parietal peritoneum), thorax (corresponding to the connective tissue lying immediately beneath the mesothelium of the parietal pleura), lung (corresponding to the connective tissue under the mesothelium of the visceral pleura), liver (corresponding to the connective tissue under the mesothelium of the visceral peritoneum), kidney (corresponding to the Gerota fascia), the oesophagus (corresponding to its adventitia) and heart (corresponding to the fibrous layer of the pericardial sac) from eight fresh cadavers were sampled and analysed with histological and immunohistochemical stains to evaluate collagen and elastic components and innervation. Although the visceral fasciae make up a well-defined layer of connective tissue, the thickness, percentage of elastic fibres and innervation vary among the different viscera. In particular, the fascia of the lung has a mean thickness of 134 μm (± 21), that of heart 792 μm (± 132), oesophagus 105 μm (± 10), liver 131 μm (± 18), Gerota fascia 1009 μm (± 105) and the visceral fascia of the abdomen 987 μm (± 90). The greatest number of elastic fibres (9.79%) was found in the adventitia of the oesophagus. The connective layers lying immediately outside the mesothelium of the pleura and peritoneum also have many elastic fibres (4.98% and 4.52%, respectively), whereas the pericardium and Gerota fascia have few (0.27% and 1.38%). In the pleura, peritoneum and adventitia of the oesophagus, elastic fibres form a well-defined layer, corresponding to the elastic lamina, while in the other cases they are thinner and scattered in the connective tissue. Collagen fibres also show precise spatial organisation, being arranged in several layers. In each layer, all the fibrous bundles are parallel with each other, but change direction among layers. Loose connective tissue rich in elastic fibres is found between contiguous fibrous layers. Unmyelinated nerve fibres were found in all samples, but myelinated fibres were only found in some fasciae, such as those of the liver and heart, and the visceral fascia of the abdomen. According to these findings, we propose distinguishing the visceral fasciae into two large groups. The first group includes all the fasciae closely related to the individual organ and giving shape to it, supporting the parenchyma; these are thin, elastic and very well innervated. The second group comprises all the fibrous sheets forming the compartments for the organs and also connecting the internal organs to the musculoskeletal system. These fasciae are thick, less elastic and less innervated, but they contain larger and myelinated nerves. We propose to call the first type of fasciae 'investing fasciae', and the second type 'insertional fasciae'. © 2017 Anatomical Society.

The "all-or-none" law in skeletal muscle and nerve fibres.

PubMed

Pareti, G

2007-01-01

In 1905 the Cambridge physiologist Keith Lucas extended the "all-or-none" principle (introduced by H. P. Bowditch for the cardiac tissue) to skeletal muscle and nerve fibres. Nevertheless, in a short time it was clear that nerve fibres obey this law, but also that frequency of discharge is another relevant factor in the nervous conduction.

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.

Cholinergic innervation of human mesenteric lymphatic vessels.

PubMed

D'Andrea, V; Bianchi, E; Taurone, S; Mignini, F; Cavallotti, C; Artico, M

2013-11-01

The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity. Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data. The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods. The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

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.

A Jones matrix formalism for simulating three-dimensional polarized light imaging of brain tissue.

PubMed

Menzel, M; Michielsen, K; De Raedt, H; Reckfort, J; Amunts, K; Axer, M

2015-10-06

The neuroimaging technique three-dimensional polarized light imaging (3D-PLI) provides a high-resolution reconstruction of nerve fibres in human post-mortem brains. The orientations of the fibres are derived from birefringence measurements of histological brain sections assuming that the nerve fibres—consisting of an axon and a surrounding myelin sheath—are uniaxial birefringent and that the measured optic axis is oriented in the direction of the nerve fibres (macroscopic model). Although experimental studies support this assumption, the molecular structure of the myelin sheath suggests that the birefringence of a nerve fibre can be described more precisely by multiple optic axes oriented radially around the fibre axis (microscopic model). In this paper, we compare the use of the macroscopic and the microscopic model for simulating 3D-PLI by means of the Jones matrix formalism. The simulations show that the macroscopic model ensures a reliable estimation of the fibre orientations as long as the polarimeter does not resolve structures smaller than the diameter of single fibres. In the case of fibre bundles, polarimeters with even higher resolutions can be used without losing reliability. When taking the myelin density into account, the derived fibre orientations are considerably improved. © 2015 The Author(s).

Behavioural, morphological and electrophysiological assessment of the effects of type 2 diabetes mellitus on large and small nerve fibres in Zucker diabetic fatty, Zucker lean and Wistar rats.

PubMed

Garcia-Perez, E; Schönberger, T; Sumalla, M; Stierstorfer, B; Solà, R; Doods, H; Serra, J; Gorodetskaya, N

2018-04-20

Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2DM). The most common presentation is in the form of a distal axonal sensory-motor polyneuropathy that involves large and small nerve fibres in variable proportion. Zucker Diabetic Fatty (ZDF), Zucker Lean (ZL) and Wistar Han (WH) rats were used to assess the behavioural, morphological and electrophysiological effects that T2DM have on peripheral large and small nerve fibres of 6- to 40-week-old rats. ZDF rats presented mechanical hypersensitivity that initially worsened in parallel to the progression of diabetes and eventually reverted at later stages of the disease. The reversal from hypersensitivity to hyposensitivity paralleled a reduction in the number of intraepithelial skin nerve terminals and in the nerve fibre lengths. However, no increased levels of degeneration of dorsal root ganglion neurons were observed. Nerve conduction studies showed a reduction in sensory and motor nerve conduction velocity (CV) in hyperglycaemic ZDF rats. Microneurography showed significant alterations in several parameters of activity-dependent slowing (ADS) of mechano-insensitive C-nociceptors in ZDF rats. Surprisingly, some of these changes were also observed in ZL rats. Moreover, we found spontaneous activity in all three strains implying that C-nociceptors become hyperexcitable and spontaneously active not only in ageing hyperglycaemic ZDF rats but also in age-matched and apparently normoglycaemic ZL and WH rats fed with the same diet. ZDF rats presented a diabetic neuropathy involving large and small nerve fibres; additionally, ZL and WH rats also showed early small abnormalities in C-fibres, clearly detected by microneurography SIGNIFICANCE: This study provides a functional description of large and small nerve fibre function in a diabetic model that recapitulates many of the findings observed in patients suffering from type 2 diabetes mellitus. © 2018 European Pain Federation - EFIC®.

Visual neuroscience before the neuron.

PubMed

Wade, Nicholas J

2004-01-01

Visual neuroscience is considered to be a contemporary concern, based in large part on relating characteristics of neural functioning to visual experience. It presupposes a detailed knowledge of neural activity for which the neuron doctrine is a fundamental tenet. However, long before either the neuron doctrine had been advanced or the nerve cell had been described, attempts were made to estimate the dimensions of nerve fibres from measures of visual resolution. In the seventeenth century, the microscopes of Hooke and van Leeuwenhoek were unable to resolve structures as small as nerves adequately. However, it was not Hooke's microscope that led to an estimate of the dimensions of nerve fibres but his experiments on the limits of visual resolution. Hooke determined that a separation of one minute of arc was the minimum that could normally be seen. Descartes had earlier speculated that the retina consisted of the terminations of fibres of the optic nerve, and that their size defined the limits of what could be seen. Estimates of the diameters of nerve fibres were made on the basis of human visual acuity by Porterfield in 1738; he calculated the diameters of nerve fibres in the retina as one 7200th part of an inch (0.0035 mm), based on the resolution of one minute of arc as the minimum visible. In the same year, Jurin questioned the reliability of such estimates because of variations in visual resolution with different stimuli. The measurement of visual acuity was refined by Mayer in 1755, with dots, gratings, and grids used as stimuli. In the 1830s, Treviranus fused the microscopic and acuity approaches to determine the dimensions of nerve fibres. His indirect estimates of the dimensions of retinal fibres were close to those derived from microscopic observation. However, the suggestion that the retina consisted of terminations of nerve fibres influenced his detailed illustrations of its microscopic structure. Contrary to the situation that obtained after the microscopic structure of the retina had been established, a function of vision (acuity) was used to determine the dimensions of the structures (retinal elements) that were thought to mediate it.

[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.)

Differentiation of vasoactive renal sympathetic nerve fibres.

PubMed

Dibona, G F

2000-01-01

Activation of renal sympathetic nerves produces marked changes in renal haemodynamics, tubular ion and water transport and renin secretion. This review examines information indicating that these effects are mediated by functionally specific groups of renal sympathetic nerve fibres separately innervating the renal vessels, tubules and juxtaglomerular granular cells.

Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging.

PubMed

Dabbah, M A; Graham, J; Petropoulos, I N; Tavakoli, M; Malik, R A

2011-10-01

Diabetic peripheral neuropathy (DPN) is one of the most common long term complications of diabetes. Corneal confocal microscopy (CCM) image analysis is a novel non-invasive technique which quantifies corneal nerve fibre damage and enables diagnosis of DPN. This paper presents an automatic analysis and classification system for detecting nerve fibres in CCM images based on a multi-scale adaptive dual-model detection algorithm. The algorithm exploits the curvilinear structure of the nerve fibres and adapts itself to the local image information. Detected nerve fibres are then quantified and used as feature vectors for classification using random forest (RF) and neural networks (NNT) classifiers. We show, in a comparative study with other well known curvilinear detectors, that the best performance is achieved by the multi-scale dual model in conjunction with the NNT classifier. An evaluation of clinical effectiveness shows that the performance of the automated system matches that of ground-truth defined by expert manual annotation. Copyright © 2011 Elsevier B.V. All rights reserved.

Distribution of adrenergic and cholinergic nerve fibres within intrinsic nerves at the level of the human heart hilum.

PubMed

Petraitiene, Viktorija; Pauza, Dainius H; Benetis, Rimantas

2014-06-01

The disbalance between adrenergic (sympathetic) and cholinergic (parasympathetic) cardiac inputs facilitates cardiac arrhythmias, including the lethal ones. In spite of the fact that the morphological pattern of the epicardiac ganglionated subplexuses (ENsubP) has been previously described in detail, the distribution of functionally distinct axons in human intrinsic nerves was not investigated thus far. Therefore, the aim of the present study was to quantitatively evaluate the distribution of tyrosine hydroxylase (TH)- and choline acetyltransferase (ChAT)-positive axons within intrinsic nerves at the level of the human heart hilum (HH), since they are of pivotal importance for determining proper treatment options for different arrhythmias. Tissue samples containing the intrinsic nerves from seven epicardiac subplexuses were obtained from nine human hearts without cardiac pathology and processed for immunofluorescent detection of TH and ChAT. The nerve area was measured and the numbers of axons were counted using microphotographs of nerve profiles. The densities of fibres were extrapolated and compared between subplexuses. ChAT-immunoreactive (IR) fibres were evidently predominant (>56%) in nerves of dorsal (DRA) and ventral right atrial (VRA) ENsubP. Within both left (LC) and right coronary ENsubP, the most abundant (70.9 and 83.0%, respectively) were TH-IR axons. Despite subplexal dependence, ChAT-IR fibres prevailed in comparatively thinner nerves, whereas TH-IR fibres in thicker ones. Morphometry showed that at the level of HH: (i) LC subplexal nerves were found to be the thickest (25 737 ± 4131 μm(2)) ones, whereas the thinnest (2604 ± 213 μm(2)) nerves concentrated in DRA ENsubP; (ii) the density of ChAT-IR axons was highest (6.8 ± 0.6/100 μm(2)) in the ventral left atrial nerves and lowest (3.2 ± 0.1/100 μm(2)) in left dorsal ENsubP and (iii) the density of TH-IR fibres was highest (15.9 ± 2.1/100 μm(2)) in LC subplexal nerves and lowest (4.4 ± 0.3/100 μm(2)) in VRA nerves. (i) The principal intrinsic adrenergic neural pathways in the human heart proceed via both coronary ENsubP that supply cardiac ventricles and (ii) the majority of cholinergic nerve fibres access the human heart through DRA and VRA ENsubP and extend towards the right atrium, including the region of the sinuatrial node. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Substance P immunoreactive nerve terminals in the dorsolateral nucleus of the tractus solitarius: roles in the baroreceptor reflex.

PubMed

Massari, V J; Shirahata, M; Johnson, T A; Lauenstein, J M; Gatti, P J

1998-03-02

Physiological and light microscopic evidence suggest that substance P (SP) may be a neurotransmitter contained in first-order sensory baroreceptor afferents; however, ultrastructural support for this hypothesis is lacking. We have traced the central projections of the carotid sinus nerve (CSN) in the cat by utilizing the transganglionic transport of horseradish peroxidase (HRP). The dorsolateral subnucleus of the nucleus tractus solitarius (dlNTS) was processed for the histochemical visualization of transganglionically labeled CSN afferents and for the immunocytochemical visualization of SP by dual labeling light and electron microscopic methods. Either HRP or SP was readily identified in single-labeled unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS. SP immunoreactivity was also identified in unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS, which were simultaneously identified as CSN primary afferents. However, only 15% of CSN terminals in the dlNTS were immunoreactive for SP. Therefore, while the ultrastructural data support the hypothesis that SP immunoreactive first-order neurons are involved in the origination of the baroreceptor reflex, they suggest that only a modest part of the total sensory input conveyed from the carotid sinus baroreceptors to the dlNTS is mediated by SP immunoreactive CSN terminals. Five types of axo-axonic synapses were observed in the dlNTS. SP immunoreactive CSN afferents were very rarely involved in these synapses. Furthermore, SP terminals were never observed to form the presynaptic element in an axo-axonic synapse with a CSN afferent. Therefore, SP does not appear to be involved in the modulation of the baroreceptor reflex in the dlNTS. Copyright 1998 Elsevier Science B.V.

Structure and innervation of the tusk pulp in the African elephant (Loxodonta africana)

PubMed Central

Weissengruber, GE; Egerbacher, M; Forstenpointner, G

2005-01-01

African elephants (Loxodonta africana) use their tusks for digging, carrying and behavioural display. Their healing ability following traumatic injury is enormous. Pain experience caused by dentin or pulp damage of tusks seems to be negligible in elephants. In this study we examined the pulp tissue and the nerve distribution using histology, electron microscopy and immunhistochemistry. The results demonstrate that the pulp comprises two differently structured regions. Randomly orientated collagen fibres characterize a cone-like part lying rostral to the foramen apicis dentis. Numerous nerve fibres and Ruffini endings are found within this cone. Rostral to the cone, delicate collagen fibres and large vessels are orientated longitudinally. The rostral two-thirds of the pulp are highly vascularized, whereas nerve fibres are sparse. Vessel and nerve fibre distribution and the structure of connective tissue possibly play important roles in healing and in the obviously limited pain experience after tusk injuries and pulp alteration. The presence of Ruffini endings is most likely related to the use of tusks as tools. PMID:15817106

Dual-model automatic detection of nerve-fibres in corneal confocal microscopy images.

PubMed

Dabbah, M A; Graham, J; Petropoulos, I; Tavakoli, M; Malik, R A

2010-01-01

Corneal Confocal Microscopy (CCM) imaging is a non-invasive surrogate of detecting, quantifying and monitoring diabetic peripheral neuropathy. This paper presents an automated method for detecting nerve-fibres from CCM images using a dual-model detection algorithm and compares the performance to well-established texture and feature detection methods. The algorithm comprises two separate models, one for the background and another for the foreground (nerve-fibres), which work interactively. Our evaluation shows significant improvement (p approximately 0) in both error rate and signal-to-noise ratio of this model over the competitor methods. The automatic method is also evaluated in comparison with manual ground truth analysis in assessing diabetic neuropathy on the basis of nerve-fibre length, and shows a strong correlation (r = 0.92). Both analyses significantly separate diabetic patients from control subjects (p approximately 0).

Aberrant nerve fibres within the central nervous system.

PubMed

Moffie, D

1992-01-01

Three cases of aberrant nerve fibres in the spinal cord and medulla oblongata are described. The literature on these fibres is discussed and their possible role in regeneration. Different views on the possibility of regeneration or functional recovery of the central nervous system are mentioned in the light of recent publications, which are more optimistic than before.

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

Vertebral body innervation: Implications for pain.

PubMed

Buonocore, Michelangelo; Aloisi, Anna Maria; Barbieri, Massimo; Gatti, Anna Maria; Bonezzi, Cesare

2010-03-01

Vertebral fractures often cause intractable pain. To define the involvement of vertebral body innervation in pain, we collected specimens from male and female patients during percutaneous kyphoplasty, a procedure used for reconstruction of the vertebral body. Specimens were taken from 31 patients (9 men and 22 women) suffering high-intensity pain before surgery. In total, 1,876 histological preparations were obtained and analysed. Immunohistochemical techniques were used to locate the nerves in the specimens. The nerve fibres were labelled by indirect immunofluorescence with the primary antibody directed against Protein Gene Product 9.5 (PGP 9.5), a pan-neuronal marker; another primary antibody directed against type IV collagen (Col IV) was used to identify vessels and to determine their relationship with vertebral nerve fibres. The mean percentage of samples in which it was possible to identify nerve fibres was 35% in men and 29% in women. The percentages varied depending on the spinal level considered and the sex of the subject, nerve fibres being mostly present around vessels (95%). In conclusion, there is scarce innervation of the vertebral bodies, with a clear prevalence of fibres located around vessels. It seems unlikely that this pattern of vertebral body innervation is involved in vertebral pain or in pain relief following kyphoplasty.

Nervus terminalis in dogfish (Squalus acanthias, Elasmobranchii) carries tonic efferent impulses.

PubMed

Bullock, T H; Northcutt, R G

1984-02-10

Recordings from the intact nervus terminalis with a hook electrode or from a stump of the divided nerve with a suction electrode show a tonic, irregular discharge of broad, low frequency spikes in ca. 4-6 units. These nerve impulses are efferent from the brain. The mean frequency of discharge is not influenced by various chemical, thermal, tactile, acoustic, photic, vibratory and electric field stimuli but is decreased by certain forms of mechanical stimuli, presumably acting on the lateral line organs of the lateral aspect of the head. We have not succeeded in recording from afferents. The nerve consists of greater than 1000 unmyelinated axons, mostly less than 1 micron, a very few greater than 1.5 micron in diameter; presumably the efferents recorded from were these larger fibers.

Photothermal modeling of thulium fibre laser-tissue interactions

NASA Astrophysics Data System (ADS)

Warnaby, Catherine E.; Coleman, Daniel J.; King, Terence A.

2003-10-01

A one-dimensional finite difference model has been used to investigate the temperature distribution within thulium fibre laser-irradiated tissue. Temperature-time and temperature-depth profiles are presented for various laser stimulus parameters in the 2 micron region. These current calculations are aimed at determining theoretical temperature distributions in the application of relatively low power fibre lasers for thermal stimulation of cutaneous nerves in human pain processing. Theoretical skin surface temperatures are compared with those from thermal camera measurements during thulium fibre laser irradiation. The effectiveness of the thulium fibre laser for thermally stimulating cutaneous nerves is confirmed.

Peptide-containing nerve fibres in the gut wall in Crohn's disease.

PubMed Central

Sjölund, K; Schaffalitzky, O B; Muckadell, D E; Fahrenkrug, J; Håkanson, R; Peterson, B G; Sundler, F

1983-01-01

Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6192043

Transverse tripolar stimulation of peripheral nerve: a modelling study of spatial selectivity.

PubMed

Deurloo, K E; Holsheimer, J; Boom, H B

1998-01-01

Various anode-cathode configurations in a nerve cuff are modelled to predict their spatial selectivity characteristics for functional nerve stimulation. A 3D volume conductor model of a monofascicular nerve is used for the computation of stimulation-induced field potentials, whereas a cable model of myelinated nerve fibre is used for the calculation of the excitation thresholds of fibres. As well as the usual configurations (monopole, bipole, longitudinal tripole, 'steering' anode), a transverse tripolar configuration (central cathode) is examined. It is found that the transverse tripole is the only configuration giving convex recruitment contours and therefore maximises activation selectivity for a small (cylindrical) bundle of fibres in the periphery of a monofascicular nerve trunk. As the electrode configuration is changed to achieve greater selectivity, the threshold current increases. Therefore threshold currents for fibre excitation with a transverse tripole are relatively high. Inverse recruitment is less extreme than for the other configurations. The influences of several geometrical parameters and model conductivities of the transverse tripole on selectivity and threshold current are analysed. In chronic implantation, when electrodes are encapsulated by a layer of fibrous tissue, threshold currents are low, whereas the shape of the recruitment contours in transverse tripolar stimulation does not change.

Assessment of nerve ultrastructure by fibre-optic confocal microscopy.

PubMed

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

1996-01-01

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

Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea.

PubMed

Hossain, Waheeda A; Antic, Srdjan D; Yang, Yang; Rasband, Matthew N; Morest, D Kent

2005-07-20

The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na+ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.

Glycogen function in adult central and peripheral nerves.

PubMed

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

2013-08-01

We studied the roles of glycogen in axonal pathways of the central nervous system (CNS) and peripheral nervous system (PNS). By using electrophysiological recordings, in combination with biochemical glycogen assay, it was possible to determine whether glycogen was crucial to axon function under different conditions. Glycogen was present both in mouse optic nerve (MON) and in mouse sciatic nerve (MSN). Aglycemia caused loss of the compound action potential (CAP) in both pathways after a latency of 15 min (MON) and 120 min for myelinated axons (A fibers) in the MSN. With the exception of unmyelinated axons (C fibers) in the MSN, CAP decline began when usable glycogen was exhausted. Glycogen was located in astrocytes in the MON and in myelinating Schwann cells in the MSN; it was absent from the Schwann cells surrounding unmyelinated C fibers. In MON, astrocytic glycogen is metabolized to lactate and "shuttled" to axons to support metabolism. The ability of lactate to support A fiber conduction in the absence of glucose suggests a common pathway in both the CNS and the PNS. Lactate is released from MON and MSN in substantial quantities. That lactate levels fall in MSN in the presence of diaminobenzidine, which inhibits glycogen phosphorylase, strongly suggests that glycogen metabolism contributes to lactate release under resting conditions. Glycogen is a "backup" energy substrate in both the CNS and the PNS and, beyond sustaining excitability during glucose deprivation, has the capacity to subsidize the axonal energy demands during times of intense activity in the presence of glucose. Copyright © 2013 Wiley Periodicals, Inc.

Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation.

PubMed

do Nascimento-Elias, Adriana Helena; Fresnesdas, Bruno César; Schiavoni, Maria Cristina Lopes; de Almeida, Natália Fernanda Gaspar; Santos, Ana Paula; de Oliveira Ramos, Jean; Junior, Wilson Marques; Barreira, Amilton Antunes

2012-08-14

Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco's modified Eagle's medium) can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM) and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth.

Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

PubMed

Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

2016-03-30

The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

PubMed Central

Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

2016-01-01

The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis. PMID:27025263

Peripheral changes in endometriosis-associated pain

PubMed Central

Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

2014-01-01

BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between elevated neurotrophin levels and pain severity seems to exist, suggesting the involvement of other mediators in the modulation of pain. CONCLUSIONS The increased expression of neuotrophic factors and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum imply a role of such peripheral changes in the pathogenesis of endometriosis-associated pain. However, a clear link between these findings and pain in patients with endometriosis has so far not been demonstrated. PMID:24859987

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

Analysis of macular and nerve fiber layer thickness in multiple sclerosis patients according to severity level and optic neuritis episodes.

PubMed

Soler García, A; Padilla Parrado, F; Figueroa-Ortiz, L C; González Gómez, A; García-Ben, A; García-Ben, E; García-Campos, J M

2016-01-01

Quantitative assessment of macular and nerve fibre layer thickness in multiple sclerosis patients with regard to expanded disability status scale (EDSS) and presence or absence of previous optic neuritis episodes. We recruited 62 patients with multiple sclerosis (53 relapsing-remitting and 9 secondary progressive) and 12 disease-free controls. All patients underwent an ophthalmological examination, including quantitative analysis of the nerve fibre layer and macular thickness using optical coherence tomography. Patients were classified according to EDSS as A (lower than 1.5), B (between 1.5 and 3.5), and C (above 3.5). Mean nerve fibre layer thickness in control, A, B, and C groups was 103.35±12.62, 99.04±14.35, 93.59±15.41, and 87.36±18.75μm respectively, with statistically significant differences (P<.05). In patients with no history of optic neuritis, history of episodes in the last 3 to 6 months, or history longer than 6 months, mean nerve fibre layer thickness was 99.25±13.71, 93.92±13.30 and 80.07±15.91μm respectively; differences were significant (P<.05). Mean macular thickness in control, A, B, and C groups was 220.01±12.07, 217.78±20.02, 217.68±20.77, and 219.04±24.26μm respectively. Differences were not statistically significant. The mean retinal nerve fibre layer thickness in multiple sclerosis patients is related to the EDSS level. Patients with previous optic neuritis episodes have a thinner retinal nerve fibre layer than patients with no history of these episodes. Mean macular thickness is not correlated to EDSS level. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Neuropeptide tyrosine (NPY)--a major cardiac neuropeptide.

PubMed

Gu, J; Polak, J M; Adrian, T E; Allen, J M; Tatemoto, K; Bloom, S R

1983-05-07

A newly discovered bioactive peptide, neuropeptide tyrosine (NPY), has been found in the human cardiac nervous system. Dense concentrations of NPY-immunoreactive nerve fibres were found in association with nodal tissue (atrioventricular node 22.1 +/- 3.7 pmol/g). NPY nerve fibres were seen in close contact with cardiac muscle fibres and were also found around the coronary vessels (19.6 +/- 6.2 pmol/g). Analysis of the peptide by high-performance liquid chromatography demonstrated that it was present in a single molecular form, closely similar or identical to that of the isolated bioactive peptide. Cardiac function in man has long been known to be influenced by cholinergic and adrenergic nerves. There now appears to be a further component of the nervous system in the human heart, involving peptidergic nerves containing NPY.

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.

Analytical theory for extracellular electrical stimulation of nerve with focal electrodes. I. Passive unmyelinated axon.

PubMed Central

Rubinstein, J T; Spelman, F A

1988-01-01

The cable model of a passive, unmyelinated fiber in an applied extracellular field is derived. The solution is valid for an arbitrary, time-varying, applied field, which may be determined analytically or numerically. Simple analytical computations are presented. They explain a variety of known phenomena and predict some previously undescribed properties of extracellular electrical stimulation. The polarization of a fiber in an applied field behaves like the output of a spatial high-pass and temporal low-pass filter of the stimulus. High-frequency stimulation results in a more spatially restricted region of fiber excitation, effectively reducing current spread relative to that produced by low-frequency stimulation. Chronaxie measured extracellularly is a function of electrode position relative to the stimulated fiber, and its value may differ substantially from that obtained intracellularly. Frequency dependence of psychophysical threshold obtained by electrical stimulation of the macaque cochlea closely follows the frequency dependence of single-fiber passive response. PMID:3233274

Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands.

PubMed

Fahrenkrug, Jan; Hannibal, Jens

2011-03-01

PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the distribution of PAC(1), VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of nerve fibres displaying PACAP-immunoreactivity were distributed beneath the capsule, around blood vessels and close to glandular cells. Most of the PACAP-nerves were sensory, since they co-stored CGRP (calcitonin-gene-related peptide) and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2) receptors occurred in the parathyroid gland, mainly located in the glandular cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated with blood vessels, thyroid follicles and parafollicular C-cells. A high degree of co-existence between PACAP and VIP (vasoactive intestinal polypeptide) was observed in the intrathyroid nerve fibres and cell bodies of the thyroid ganglion indicating a common origin for the two peptides. A minor population of PACAP-immunoreactive nerve fibres with relation to blood vessels co-stored NPY (neuropeptide Y), whereas only a few fibres co-stored CGRP. PAC(1) and VPAC(1) receptor mRNA's occurred in follicular cells and blood vessels, whereas the expression of the VPAC(2) receptor was low. The findings suggest that PACAP plays a role in the regulation of parathyroid and thyroid blood flow and hormone secretion. Copyright © 2010 Elsevier Inc. All rights reserved.

Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.

PubMed

Facer, Paul; Punjabi, Prakash P; Abrari, Andleeb; Kaba, Riyaz A; Severs, Nicholas J; Chambers, John; Kooner, Jaspal S; Anand, Praveen

2011-01-01

We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

Immunocytochemical demonstration of neuropeptides in the fish-gill parasite, Diclidophora merlangi (Monogenoidea).

PubMed

Maule, A G; Halton, D W; Johnston, C F; Fairweather, I; Shaw, C

1989-05-01

Using the indirect immunofluorescence technique, immunoreactivity (IR) to three mammalian and one invertebrate regulatory peptide has been demonstrated in the nervous system of the monogenean gill parasite Diclidophora merlangi. IR to pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY) and FMRFamide was evident throughout central and peripheral nervous tissues, whereas vasoactive intestinal polypeptide (VIP)-IR was confined to a portion of the longitudinal ventral nerve cords. Staining patterns revealed the orthogonal arrangement of the nervous system consisting of paired cerebral ganglia, connecting post-pharyngeal commissure, three pairs of longitudinal nerve cords and associated neurones. PP-IR, PYY-IR and FMRFamide-IR were intense throughout the central nervous system of the worm. A small plexus of nerve fibres and somata in each peduncle was immunoreactive for FMRFamide and provided innervation to each of the eight posterior clamps. In the peripheral nervous system, PP-IR, PYY-IR and FMRFamide-IR occurred in an extensive nerve-net with fine, possibly sensory nerve endings in the tegument. PP-IR was also present in nerve fibres in the walls of the ootype, seminal vesicle and uterus. PYY- and FMRFamide-IRs, while evident in nerve fibres of the ootype wall, were also present in a distinct population of cells that encircles the ootype, and which are linked to it by fine cytoplasmic connectives. The majority of these somata were bipolar or multipolar. PYY-IR and FMRFamide-IR were also associated with nerve fibres and bipolar cells in the wall of the vitelline reservoir. Regulatory peptides would appear to play an integral role in neuronal functioning and egg development in D. merlangi.

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.

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.

Histochemistry of nerve fibres double labelled with anti-TRPV2 antibodies and sensory nerve marker AM1-43 in the dental pulp of rat molars.

PubMed

Nishikawa, Sumio

2008-09-01

AM1-43 can label sensory nerve fibres and sensory neurons. Permeation of non-selective cation channels of the nerve cell membrane is suggested to be the mechanism responsible for labelling. To identify these channels, two candidates, TRPV1 and TRPV2 were examined by immunocytochemistry in the dental pulp and trigeminal ganglion of rats injected with AM1-43. A part of AM1-43-labelled nerve fibres was also positive for anti-TRPV2 antibody but negative for anti-TRPV1 antibody in the dental pulp. In the trigeminal ganglion, a part of the neuron showed both bright AM1-43 labelling and anti-TRPV2 immunolabelling, but neurons double labelled with AM1-43 and TRPV1 were rare. These results suggest that TRPV2 channels, but not TRPV1 channels, contribute to the fluorescent labelling of AM1-43 in the dental pulp.

Optic neuropathies--importance of spatial distribution of mitochondria as well as function.

PubMed

Yu Wai Man, C Y; Chinnery, P F; Griffiths, P G

2005-01-01

Optic neuropathies such as Leber's hereditary optic neuropathy, dominant optic atrophy and toxic amblyopia are an important cause of irreversible visual failure. Although they are associated with a defect of mitochondrial energy production, their pathogenesis is poorly understood. A common feature to all these disorders is relatively selective degeneration of the papillomacular bundle of retinal ganglion cells resulting central or caecocentral visual field defects. The striking similarity in the pattern of clinical involvement seen with these disparate disorders suggests a common pathway in their aetiology. The existing hypothesis that the optic nerve head has higher energy demands than other tissues making it uniquely dependent on oxidative phosporylation is not satisfactory. First, other ocular tissues such as photoreceptors, which are more dependent on oxidative phosporylation are not affected. Second, other mitochondrial disorders, which have a greater impact on mitochondrial energy function, do not affect the optic nerve. The optic nerve head has certain unique ultra structural features. Ganglion cell axons exit the eye through a perforated collagen plate, the lamina cribrosa. There is a sharp discontinuity in the density of mitochondria at the optic nerve head, with a very high concentration in the prelaminar nerve fibre layer and low concentration behind the lamina. This has previously been attributed to a mechanical hold up of axoplasmic flow, which has itself been proposed as a factor in the pathogenesis of a number of optic neuropathies. More recent evidence shows that mitochondrial distribution reflects the different energy requirements of the unmyelinated prelaminar axons in comparison to the myelinated retrolaminar axons. The heterogeous distribution of mitochondria is actively maintained to support conduction through the optic nerve head. We propose that factors that disrupt the heterogeneous distribution of mitochondria can result in ganglion cell death. Evidence for this comes from studies of cultured cells with the dominant optic atrophy mutation in which mitochondrial distribution is altered and from some forms of hereditary spastic paraparesis which are associated with optic atrophy. The responsible mutations do not affect ATP production until late in the disease but do affect mitochondrial arrangement, again showing that mitochondrial distribution as well as energy production by individual mitochondria may be important in the pathogenesis of ganglion cell death. Greater understanding of the factors localising mitochondria within the ganglion cell axon in particular the interaction with cytoskeleton is required to formulate new treatments. Boosting energy production alone may not be an effective treatment.

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.

PubMed

Hinder, Lucy M; Park, Meeyoung; Rumora, Amy E; Hur, Junguk; Eichinger, Felix; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

2017-09-01

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Improved sampling and analysis of images in corneal confocal microscopy.

PubMed

Schaldemose, E L; Fontain, F I; Karlsson, P; Nyengaard, J R

2017-10-01

Corneal confocal microscopy (CCM) is a noninvasive clinical method to analyse and quantify corneal nerve fibres in vivo. Although the CCM technique is in constant progress, there are methodological limitations in terms of sampling of images and objectivity of the nerve quantification. The aim of this study was to present a randomized sampling method of the CCM images and to develop an adjusted area-dependent image analysis. Furthermore, a manual nerve fibre analysis method was compared to a fully automated method. 23 idiopathic small-fibre neuropathy patients were investigated using CCM. Corneal nerve fibre length density (CNFL) and corneal nerve fibre branch density (CNBD) were determined in both a manual and automatic manner. Differences in CNFL and CNBD between (1) the randomized and the most common sampling method, (2) the adjusted and the unadjusted area and (3) the manual and automated quantification method were investigated. The CNFL values were significantly lower when using the randomized sampling method compared to the most common method (p = 0.01). There was not a statistical significant difference in the CNBD values between the randomized and the most common sampling method (p = 0.85). CNFL and CNBD values were increased when using the adjusted area compared to the standard area. Additionally, the study found a significant increase in the CNFL and CNBD values when using the manual method compared to the automatic method (p ≤ 0.001). The study demonstrated a significant difference in the CNFL values between the randomized and common sampling method indicating the importance of clear guidelines for the image sampling. The increase in CNFL and CNBD values when using the adjusted cornea area is not surprising. The observed increases in both CNFL and CNBD values when using the manual method of nerve quantification compared to the automatic method are consistent with earlier findings. This study underlines the importance of improving the analysis of the CCM images in order to obtain more objective corneal nerve fibre measurements. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Observations on the responses of muscle to mechanical and electrical stimuli

PubMed Central

Meadows, J. C.

1971-01-01

Responses to mechanical and electrical stimuli have been studied in vastus medialis in four young adults. Percussion causes an immediate, brief contraction in those muscle fibres passing beneath the site of the blow. This is accompanied by EMG activity which is propagated along the muscle fibres at a normal velocity of around 4 m/sec. The EMG activity lasts much longer than that produced by a single electrical stimulus to muscle fibres because repetitive firing occurs in some of the muscle fibres activated mechanically. This response to percussion is unaffected by nerve blockade with 2% xylocaine. Percussion close to the motor point may cause delayed fasciculation due to activation of intramuscular motor nerve fibres. This, too, is unaffected by nerve blockade. Some observations on EMG insertional activity provoked by needle movement are reported. It is concluded that muscle has a basic tendency to discharge repetitively when stimulated by mechanical means and that EMG insertional activity and the EMG response to percussion reported in this paper are both manifestations of this same tendency, which is increased in the myotonias. Images PMID:4251668

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.

Afferent Nerve Regulation of Bladder Function in Health and Disease

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2012-01-01

The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling

PubMed Central

Vetter, Irina; Touska, Filip; Hess, Andreas; Hinsbey, Rachel; Sattler, Simon; Lampert, Angelika; Sergejeva, Marina; Sharov, Anastasia; Collins, Lindon S; Eberhardt, Mirjam; Engel, Matthias; Cabot, Peter J; Wood, John N; Vlachová, Viktorie; Reeh, Peter W; Lewis, Richard J; Zimmermann, Katharina

2012-01-01

Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by targeting specific unmyelinated and myelinated primary sensory neurons. These include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously expressed TRPA1, but when co-expressed with Nav channels, sodium channel activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that is responsible for the development of cold allodynia, as evidenced by a large reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1-deficient mice, confirming an important role for TRPA1 in the pathogenesis of cold allodynia. PMID:22850668

Electron microscopy of human peripheral nerves of clinical relevance to the practice of nerve blocks. A structural and ultrastructural review based on original experimental and laboratory data.

PubMed

Reina, M A; Arriazu, R; Collier, C B; Sala-Blanch, X; Izquierdo, L; de Andrés, J

2013-12-01

The goal is to describe the ultrastructure of normal human peripheral nerves, and to highlight key aspects that are relevant to the practice of peripheral nerve block anaesthesia. Using samples of sciatic nerve obtained from patients, and dural sac, nerve root cuff and brachial plexus dissected from fresh human cadavers, an analysis of the structure of peripheral nerve axons and distribution of fascicles and topographic composition of the layers that cover the nerve is presented. Myelinated and unmyelinated axons, fascicles, epineurium, perineurium and endoneurium obtained from patients and fresh cadavers were studied by light microscopy using immunohistochemical techniques, and transmission and scanning electron microscopy. Structure of perineurium and intrafascicular capillaries, and its implications in blood-nerve barrier were revised. Each of the anatomical elements is analyzed individually with regard to its relevance to clinical practice to regional anaesthesia. Routine practice of regional anaesthetic techniques and ultrasound identification of nerve structures has led to conceptions, which repercussions may be relevant in future applications of these techniques. In this regard, the ultrastructural and histological perspective accomplished through findings of this study aims at enlightening arising questions within the field of regional anaesthesia. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Different role of TTX-sensitive voltage-gated sodium channel (NaV 1) subtypes in action potential initiation and conduction in vagal airway nociceptors.

PubMed

Kollarik, M; Sun, H; Herbstsomer, R A; Ru, F; Kocmalova, M; Meeker, S N; Undem, B J

2018-04-15

The action potential initiation in the nerve terminals and its subsequent conduction along the axons of afferent nerves are not necessarily dependent on the same voltage-gated sodium channel (Na V 1) subunits. The action potential initiation in jugular C-fibres within airway tissues is not blocked by TTX; nonetheless, conduction of action potentials along the vagal axons of these nerves is often dependent on TTX-sensitive channels. This is not the case for nodose airway Aδ-fibres and C-fibres, where both action potential initiation and conduction is abolished by TTX or selective Na V 1.7 blockers. The difference between the initiation of action potentials within the airways vs. conduction along the axons should be considered when developing Na V 1 blocking drugs for topical application to the respiratory tract. The action potential (AP) initiation in the nerve terminals and its subsequent AP conduction along the axons do not necessarily depend on the same subtypes of voltage-gated sodium channels (Na V 1s). We evaluated the role of TTX-sensitive and TTX-resistant Na V 1s in vagal afferent nociceptor nerves derived from jugular and nodose ganglia innervating the respiratory system. Single cell RT-PCR was performed on vagal afferent neurons retrogradely labelled from the guinea pig trachea. Almost all of the jugular neurons expressed the TTX-sensitive channel Na V 1.7 along with TTX-resistant Na V 1.8 and Na V 1.9. Tracheal nodose neurons also expressed Na V 1.7 but, less frequently, Na V 1.8 and Na V 1.9. Na V 1.6 were expressed in ∼40% of the jugular and 25% of nodose tracheal neurons. Other Na V 1 α subunits were only rarely expressed. Single fibre recordings were made from the vagal nodose and jugular nerve fibres innervating the trachea or lung in the isolated perfused vagally-innervated preparations that allowed for selective drug delivery to the nerve terminal compartment (AP initiation) or to the desheathed vagus nerve (AP conduction). AP initiation in jugular C-fibres was unaffected by TTX, although it was inhibited by Na V 1.8 blocker (PF-01247324) and abolished by combination of TTX and PF-01247324. However, AP conduction in the majority of jugular C-fibres was abolished by TTX. By contrast, both AP initiation and conduction in nodose nociceptors was abolished by TTX or selective Na V 1.7 blockers. Distinction between the effect of a drug with respect to inhibiting AP in the nerve terminals within the airways vs. at conduction sites along the vagus nerve is relevant to therapeutic strategies involving inhaled Na V 1 blocking drugs. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

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

PubMed

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

2018-07-01

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

In vivo exposure to nitrogen dioxide (NO2) induces a decrease in calcitonin gene-related peptide (CGRP) and tachykinin immunoreactivity in guinea-pig peripheral airways.

PubMed

Lucchini, R E; Springall, D R; Chitano, P; Fabbri, L M; Polak, J M; Mapp, C E

1996-09-01

The mammalian respiratory tract is densely innervated by sensory and autonomic fibres. Subsets of the nerves contain bioactive regulatory peptides, such as substance P, calcitonin gene-related peptide (CGRP), and neurokinins. The sensory nervous system responds to inhaled irritants, resulting in a release of neuropeptides and, thus, a decrease in the peptide immunoreactivity of the fibres. We examined the effects of inhaled nitrogen dioxide (NO2), a well-known indoor and outdoor air pollutant, on pulmonary sensory neuropeptides. Guinea-pigs were exposed for 4 h to 18 parts per million (ppm) NO2 or to air (n = 5 each). At the end of the exposure, they were killed with urethane and their lungs were fixed in 1% paraformaldehyde in phosphate-buffered saline. Cryostat sections were stained with antisera to an anatomical nerve marker, protein gene product (PGP) 9.5, and to CGRP and tachykinins, utilizing the avidin-biotinylated peroxidase method. In the noncartilaginous airways (diameter < 250 microns) of NO2-exposed animals, less tachykinin- and CGRP-immunoreactive nerve fibres were found compared with controls. No change was seen in the total nerve fibre distribution (PGP 9.5). It is concluded that the peptidergic nerves of guinea-pig peripheral airways are a sensitive indicator of exposure to nitrogen dioxide.

Organisation of autonomic nervous structures in the small intestine of chinchilla (Chinchilla laniger, Molina).

PubMed

Nowak, E

2014-08-01

Using histochemical, histological and immunocytochemical methods, organisation of the autonomic nerve structures in small intestine of chinchilla was investigated. Myenteric plexus was localised between circular and longitudinal layers of the smooth muscles. Forming network nodes, the small autonomic, cholinergic ganglia were linked with the bundles of nerve fibres. Adrenergic structures were visible as specific varicose, rosary-like fibres forming bundles of parallel fibres connecting network nodes. Structures of the submucosal plexus formed a finer network than those of the myenteric plexus. Moreover, in 'whole-mount' specimens, fibres forming thick perivascular plexuses were also observed. Immunocytochemical studies confirmed the cholinergic and adrenergic character of the investigated structures. VAChT-positive neurones were found only in myenteric plexus, and numerous VAChT-positive and DBH-positive fibres were found in both plexuses. © 2013 Blackwell Verlag GmbH.

Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder.

PubMed

Wang, H F; Shortland, P; Park, M J; Grant, G

1998-11-01

In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with myelinated fibres). Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.

The sympathetic postganglionic fibre and the block by bretylium; the block prevented by hexamethonium and imitated by mecamylamine

PubMed Central

Burn, J. H.; Gibbons, W. R.

1964-01-01

Acetylcholine, in the presence of atropine, has an action like that of sympathetic stimulation. When injected into the splenic artery it causes contraction of the spleen, but this action is blocked by hexamethonium; stimulation of the splenic nerves, however, is still effective. Thus hexamethonium distinguishes between sympathetic nerve stimulation and the action of acetylcholine. If bretylium is used instead of hexamethonium, there is no such distinction, for bretylium blocks the response to nerve stimulation as well as that to acetylcholine. It appeared that hexamethonium might block the action of acetylcholine by preventing its entry into the sympathetic fibre. Acetylcholine has some structural similarity to bretylium, since acetylcholine is a derivative of trimethylammonium and bretylium is a derivative of dimethylethylammonium. It has been found that hexamethonium, pentolinium and hemicholinium (HC-3), which are all bis-quaternary compounds, block the action of bretylium, presumably by preventing its entry into the fibre. Consistent with the view that ability to enter the fibre is important is the observation that mecamylamine and pempidine, which are ganglion-blocking agents, but not either mono- or bis-quaternary compounds, often abolish the response to stimulation of the sympathetic postganglionic fibre. PMID:14211685

Nerve injury affects the capillary supply in rat slow and fast muscles differently.

PubMed

Cebasek, Vita; Radochová, Barbora; Ribaric, Samo; Kubínová, Lucie; Erzen, Ida

2006-02-01

The goal of this study was to determine the acute effects of permanent denervation on the length density of the capillary network in rat slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles and the effect of short-lasting reinnervation in slow muscle only. Denervation was performed by cutting the sciatic nerve. Both muscles were excised 2 weeks later. Reinnervation was studied 4 weeks after nerve crush in SOL muscle only. Capillaries and muscle fibres were visualised by triple immunofluorescent staining with antibodies against CD31 and laminin and with fluorescein-labelled Griffonia (Bandeira) simplicifolia lectin. A recently developed stereological approach allowing the estimation of the length of capillaries adjacent to each individual fibre (Lcap/Lfib) was employed. Three-dimensional virtual test grids were applied to stacks of optical images captured with a confocal microscope and their intersections with capillaries and muscle fibres were counted. Interrelationships among capillaries and muscle fibres were demonstrated with maximum intensity projection of the acquired stacks of optical images. The course of capillaries in EDL seemed to be parallel to the fibre axes, whereas in SOL, their preferential direction deviated from the fibre axes and formed more cross-connections among neighbouring capillaries. Lcap/Lfib was clearly reduced in denervated SOL but remained unchanged in EDL, although the muscle fibres significantly atrophied in both muscle types. When soleus muscle was reinnervated, capillary length per unit fibre length was completely restored. The physiological background for the different responses of the capillary network in slow and fast muscle is discussed.

Severe diffuse axon injury in chronic alcoholic rat medulla oblongata following a concussion blow.

PubMed

Luo, Jianming; Chen, Guang; Wei, Lai; Qian, Hong; Lai, Xiaoping; Wang, Dian; Lv, Junyao; Yu, Xiaojun

2014-01-01

We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05). (a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

Some intrinsic neurons of the guinea-pig heart contain substance P.

PubMed

Bałuk, P; Gabella, G

1989-10-09

Whole-mount preparations of the posterior wall of the atria of the guinea pig heart containing intrinsic ganglion cells and nerve plexuses were stained for substance P-like immunoreactivity by the peroxidase-antiperoxidase method. Substance P-like nerve fibres are present as pericellular baskets around most, but not all, of the neuronal cell bodies, and are also found in the connecting nerve bundles, as perivascular nerve plexuses and in the myocardium and pericardium. The majority of ganglion cell bodies are negative for substance P, as reported previously, but we describe for the first time, a small subpopulation of intrinsic neuronal cell bodies which show immunoreactivity for substance P. Therefore, not all cardiac substance P nerves are extrinsic afferent fibres. At present, the physiological role of intrinsic substance P neurones is not clear.

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.

The deep muscular plexus of the pig duodenum: a histochemical and ultrastructural study with special reference to the interstitial cells.

PubMed

Henry, M; Porcher, C; Julé, Y

1998-06-10

The aim of the present study was to describe the deep muscular plexus of the pig duodenum and to characterize its cellular components. Numerous nerve varicosities have been detected in the deep muscular plexus using anti-synaptophysin antibodies. Nerve fibres were also detected here in the outer circular muscle layer, whereas no nerve fibres were observed in the inner circular muscle layer. In the deep muscular plexus, nerve fibres projected to interstitial cells which were characterized at the ultrastructural level. The interstitial cells were of two kinds: the interstitial fibroblastic-like cells (FLC) and the interstitial dense cells (IDC), both of which were interposed between nerve fibres and smooth muscle cells. The FLC were characterized by their elongated bipolar shape, the lack of basal lamina, a well-developed endoplasmic reticulum, a Golgi apparatus, and intermediate filaments. They were closely apposed to axon terminals containing small clear synaptic vesicles and/or dense-cored vesicles. They were frequently connected to each other and to smooth muscle cells of the inner and outer circular layer by desmosomes and more rarely by gap junctions. The IDC are myoid-like cells. They had a stellate appearance and were characterized by a dense cell body, numerous caveolae, and a discontinuous basal lamina. The IDC were always closely apposed to nerve fibres and were connected to smooth muscle cells by desmosomes and small gap junctions. The present results show the unique pattern of cellular organization of the deep muscular plexus of the pig small intestine. They suggest that the interstitial cells in the deep muscular plexus are involved in the integration and transmission of nervous inputs from myenteric neurons to the inner and outer circular muscle layers. The clear-cut distinction observed here between the two types of interstitial cells (fibroblastic and myoid-like) suggests that the interstitial cells of each type may also be involved in some other specific activity, which still remains to be determined.

Assessing sudomotor impairment in patients with peripheral neuropathy: Comparison between electrochemical skin conductance and skin biopsy.

PubMed

Duchesne, Mathilde; Richard, Laurence; Vallat, Jean-Michel; Magy, Laurent

2018-04-27

Sudoscan provides a rapid assessment of sudomotor function based on the measurement of electrochemical skin conductance (ESC), which is thought to be proportional to small nerve fibres innervating the sweat glands. However, the relationship between ESC and small nerve fibre density on skin biopsy remains unclear. In a retrospective single-centre study, we compared ESC measurements with autonomic sweat gland nerve fibre density (SGNFD) and somatic intraepidermal nerve fibre density (IENFD) in patients with polyneuropathy. 63 patients were included (mean age: 60.6 ± 13.3 years). ESC was more strongly correlated with SGNFD (r = 0.49; p = 0.0005) than with IENFD (r = 0.42; p = 0.0005). Foot ESC was lower in patients with abnormal SGNFD (1.0 ± 0.3 µS/kg versus 0.7 ± 0.4 µS/kg; p = 0.0419) or abnormal IENFD (1.1 ± 0.3 µS/kg versus 0.8 ± 0.3 µS/kg; p = 0.0425). ESC measurement is a novel method of potential value for assessing sudomotor function. More studies are required to define its place beside ancient well-established techniques. The weak correlation of ESC with skin biopsy results suggests that mechanisms other than the loss of innervating fibres may be responsible for sweat gland dysfunction in polyneuropathies. Copyright © 2018. Published by Elsevier B.V.

Effect of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres.

PubMed

Simon, Magda; Porter, Rebecca; Brown, Robert; Coulton, Gary R; Terenghi, Giorgio

2003-11-01

We investigated whether neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) affected the reinnervation of slow and fast motor units. Neurotrophin-impregnated or plain fibronectin (FN) conduits were inserted into a sciatic nerve gap. Fast extensor digitorum longus (EDL) and slow soleus muscles were collected 4 months postsurgery. Muscles were weighed and fibre type proportion and mean fibre diameters were derived from muscle cross-sections. All fibre types in muscles from FN animals were severely atrophied and this correlated well with type 1 fibre loss and atrophy in soleus and type 2b loss and atrophy in EDL. Treatment with NT-4 reversed soleus but not EDL mass loss above the FN group by significantly restoring type 1 muscle fibre proportion and diameters towards those of normal unoperated animals. BDNF did not increase muscle mass but did have minor effects on fibre type and diameter. Thus, NT-4 significantly improved slow motor unit recovery, and provides a basis for therapies intended to aid the functional recovery of muscles after denervating injury.

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

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

PubMed

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

2017-08-01

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

Whole-Mount Adult Ear Skin Imaging Reveals Defective Neuro-Vascular Branching Morphogenesis in Obese and Type 2 Diabetic Mouse Models.

PubMed

Yamazaki, Tomoko; Li, Wenling; Yang, Ling; Li, Ping; Cao, Haiming; Motegi, Sei-Ichiro; Udey, Mark C; Bernhard, Elise; Nakamura, Takahisa; Mukouyama, Yoh-Suke

2018-01-11

Obesity and type 2 diabetes are frequently associated with peripheral neuropathy. Though there are multiple methods for diagnosis and analysis of morphological changes of peripheral nerves and blood vessels, three-dimensional high-resolution imaging is necessary to appreciate the pathogenesis with an anatomically recognizable branching morphogenesis and patterning. Here we established a novel technique for whole-mount imaging of adult mouse ear skin to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels. Whole-mount immunostaining of adult mouse ear skin showed that peripheral sensory and sympathetic nerves align with large-diameter blood vessels. Diet-induced obesity (DIO) mice exhibit defective vascular smooth muscle cells (VSMCs) coverage, while there is no significant change in the amount of peripheral nerves. The leptin receptor-deficient db/db mice, a severe obese and type 2 diabetic mouse model, exhibit defective VSMC coverage and a large increase in the amount of smaller-diameter nerve bundles with myelin sheath and unmyelinated nerve fibers. Interestingly, an increase in the amount of myeloid immune cells was observed in the DIO but not db/db mouse skin. These data suggest that our whole-mount imaging method enables us to investigate the neuro-vascular and neuro-immune phenotypes in the animal models of obesity and diabetes.

Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study.

PubMed

Azmi, Shazli; Ferdousi, Maryam; Alam, Uazman; Petropoulos, Ioannis N; Ponirakis, Georgios; Marshall, Andrew; Asghar, Omar; Fadavi, Hassan; Jones, Wendy; Tavakoli, Mitra; Boulton, Andrew J M; Jeziorska, Maria; Soran, Handrean; Efron, Nathan; Malik, Rayaz A

2017-06-01

The aim of this study was to identify the contribution of small- and large-fibre neuropathy to erectile dysfunction in men with type 1 diabetes mellitus. A total of 70 participants (29 without and 41 with erectile dysfunction) with type 1 diabetes and 34 age-matched control participants underwent a comprehensive assessment of large- and small-fibre neuropathy. The prevalence of erectile dysfunction in participants with type 1 diabetes was 58.6%. After adjusting for age, participants with type 1 diabetes and erectile dysfunction had a significantly higher score on the Neuropathy Symptom Profile (mean ± SEM 5.3 ± 0.9 vs 1.8 ± 1.2, p = 0.03), a higher vibration perception threshold (18.3 ± 1.9 vs 10.7 ± 2.4 V, p = 0.02), and a lower sural nerve amplitude (5.0 ± 1.1 vs 11.7 ± 1.5 mV, p = 0.002), peroneal nerve amplitude (2.1 ± 0.4 vs 4.7 ± 0.5 mV, p < 0.001) and peroneal nerve conduction velocity (34.8 ± 1.5 vs 41.9 ± 2.0 m/s, p = 0.01) compared with those without erectile dysfunction. There was also evidence of a marked small-fibre neuropathy with an impaired cold threshold (19.7 ± 1.4°C vs 27.3 ± 1.8°C, p = 0.003), warm threshold (42.9 ± 0.8°C vs 39.0 ± 0.9°C, p = 0.005) and heart rate variability (21.5 ± 3.1 vs 30.0 ± 3.7 beats/min, p = 0.001) and reduced intraepidermal nerve fibre density (2.8 ± 0.7 vs 5.9 ± 0.7/mm, p = 0.008), corneal nerve fibre density (12.6 ± 1.5 vs 23.9 ± 2.0/mm 2 , p < 0.001), corneal nerve branch density (12.7 ± 2.5 vs 31.6 ± 3.3/mm 2 , p < 0.001) and corneal nerve fibre length (8.3 ± 0.7 vs 14.5 ± 1.0 mm/mm 2 , p < 0.001) in participants with type 1 diabetes and erectile dysfunction. Erectile dysfunction correlated significantly with measures of both large- and small-fibre neuropathy. Small-fibre neuropathy is prominent in patients with type 1 diabetes, and is associated with erectile dysfunction and can be objectively quantified using corneal confocal microscopy. This may allow the identification of patients who are less likely to respond to conventional therapies such as phosphodiesterase type 5 inhibitors.

Hyposensitivity of C-fiber Afferents at the Distal Extremities as an Indicator of Early Stages Diabetic Bladder Dysfunction in Type 2 Diabetic Women

PubMed Central

Lee, Wei-Chia; Wu, Han-Ching; Huang, Kuo-How; Wu, Huey-Peir; Yu, Hong-Jeng; Wu, Chia-Ching

2014-01-01

Purpose To investigate the relationship between distal symmetric peripheral neuropathy and early stages of autonomic bladder dysfunction in type 2 diabetic women. Materials and Methods A total of 137 diabetic women with minimal coexisting confounders of voiding dysfunction followed at a diabetes clinic were subject to the following evaluations: current perception threshold (CPT) tests on myelinated and unmyelinated nerves at the big toe for peroneal nerve and middle finger for median nerve, uroflowmetry, post-void residual urine volume, and overactive bladder (OAB) symptom score questionnaire. Patients presenting with voiding difficulty also underwent urodynamic studies and intravesical CPT tests. Results Based on the OAB symptom score and urodynamic studies, 19% of diabetic women had the OAB syndrome while 24.8% had unrecognized urodynamic bladder dysfunction (UBD). The OAB group had a significantly greater mean 5 Hz CPT test value at the big toe by comparison to those without OAB. When compared to diabetic women without UBD, those with UBD showed greater mean 5 Hz CPT test values at the middle finger and big toe. The diabetic women categorized as C-fiber hyposensitivity at the middle finger or big toe by using CPT test also had higher odds ratios of UBD. Among diabetic women with UBD, the 5 Hz CPT test values at the big toe and middle finger were significantly associated with intravesical 5 Hz CPT test values. Conclusions Using electrophysiological evidence, our study revealed that hyposensitivity of unmyelinated C fiber afferents at the distal extremities is an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women. The C fiber dysfunction at the distal extremities seems concurrent with vesical C-fiber neuropathy and may be a sentinel for developing early diabetic bladder dysfunction among female patients. PMID:24466107

The foetal pig pineal gland is richly innervated by nerve fibres containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY, but it does not secrete melatonin.

PubMed

Bulc, Michał; Lewczuk, Bogdan; Prusik, Magdalena; Całka, Jarosław

2013-05-01

Innervation of the mammalian pineal gland during prenatal development is poorly recognized. Therefore, immunofluorescence studies of the pineals of 70- and 90-day-old foetuses of the domestic pig were performed using antibodies against tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH), neuropeptide Y (NPY) and C-terminal flanking peptide of NPY (CPON). The investigated glands were supplied by numerous nerve fibres containing TH and DβH. The density of these fibres was higher in the distal and middle parts of the gland than in the proximal one. NPY and CPON were identified in the majority of DβH-positive fibres as well as in a small population of DβH-negative fibres localized mainly in the proximal part of the pineal. The immunoreactive fibres were more numerous in 90-day-old foetuses than in 70-day-old ones. The effect of norepinephrine on melatonin secretion by the foetal pineals in the short-term organ culture was studied to determine the role of DβH-positive fibres during prenatal life. For the same purpose melatonin was measured in the blood in the umbilical cords and in the jugular vein of the mother. The pineals of both groups of foetuses did not secrete melatonin in the organ culture, independently of the presence or absence of norepinephrine in the medium. Melatonin concentrations in the blood in the umbilical cords of foetuses from the same litter and in the jugular vein of their mother were similar. The presence of adrenergic nerve fibres in the pig pineal during gestation does not seem to be associated with the control of melatonin secretion.

A multiparametric assay for quantitative nerve regeneration evaluation.

PubMed

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

2005-08-01

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

Ischaemia-reperfusion injury in central retinal artery occlusion.

PubMed

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-10-21

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90.

Ischaemia-reperfusion injury in central retinal artery occlusion

PubMed Central

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-01-01

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90. PMID:24145508

Neuropeotide Y changes the excitability of fine afferent units in the rat knee joint

PubMed Central

Just, Stefan; Heppelmann, Bernd

2001-01-01

The aim of the present study was to examine the effects of the sympathetic co-transmitter Neuropeotide Y on primary afferent nerve fibres of the rat knee joint. The responses to passive joint rotations at defined torque were recorded from 41 slowly conducting afferent nerve fibres (0.9 – 18.8 m s−1) innervating the knee joint capsule. About 70% of the joint afferents were significantly affected in their mechanosensitivity by topical application of Neuropeptide Y. Significant effects occurred at a concentration of 10 nM. Decreased mechanosensitivity was observed in about 40% of nerve fibres, whereas 30% of the units increased the mechanosensitivity. In addition, in about 35% of the fibres resting activity was induced or increased. Neither the conduction velocity nor the mechanical threshold of the units correlated with the described effects of Neuropeptide Y. NPY(13 – 36), a specific Y2-receptor agonist, only modulated the mechanosensitivity, with no effect on the resting activity. The effects on the mechanosensitivity were similar to Neuropeptide Y, i.e. increase and decrease of the response. Studies with the Y1-agonist (Leu31, Pro34)-NPY showed that activation of the Y1-receptor predominantly resulted in an enhanced mechanosensitivity and an induction or increase of a resting activity. The opposite effect was observed by application of BIBP 3226 BS, a Y1-receptor antagonist. In conclusion, these data indicate that Neuropeptide Y affects the excitability of sensory nerve fibre endings. PMID:11159723

Distributions of nerve and muscle fibre types in locust jumping muscle.

PubMed

Hoyle, G

1978-04-01

Muscle fibres of the locust extensor tibiae (jumping muscle) were examined by interference microscopy and by electron microscopy. The electrical responses of single fibres and the mechanical responses of bundles or selected regions to the nerve fibres were examined. Four axons innervate the muscle: fast (FETi), slow (SETi), common inhibitor (CI) and dorsal unpaired median (DUMETi). Their distributions were examined by combined electrophysiological tracing and EM sectioning. The mean diameter of muscle fibres in different regions varies from 40 to 140 micrometer and is related to the local leg thickness rather than muscle fibre type. The fine structure of a fibre is related to its innervation. Fibres innervated by FETi but not SETi are of fast type ultrastructurally. Fibres innervated by SETi but not by FETi are of slow type ultrastructurally. Fibres innervated by both axons are generally intermediate between the extremes though more nearly of fast type than slow. Distal slow muscle fibres have much slower relaxation rates than do proximal ones. The most proximal bundles are of mixed muscle fibre type. There is an abrupt transition from a mixed population to homogeneous fast type, in the muscle units immediately distal to the most proximal bundles. This transition is associated with the presence of DUMETi terminals on some of the fibres distal to the transition point. There are no SETi endings on these same fibres. Fibres innervated by both SETi and FETi are scattered throughout the leg, but are commonest in the dorsal bundles. The percentage of these increases progressively passing distally. The most distal muscle fibres are innervated by SETi but not by FETi. It is concluded that different regions of the muscle will play different roles functionally since they are differentially sensitive to the pattern of SETi discharge.

Presynaptic control of transmission along the pathway mediating disynaptic reciprocal inhibition in the cat

PubMed Central

Enríquez-Denton, M; Nielsen, J; Perreault, M-C; Morita, H; Petersen, N; Hultborn, H

2000-01-01

In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. Conditioning stimulation of flexor, but not ankle extensor, nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This depression lasted between 200 and 700 ms and was not accompanied by a depression of the monosynaptic EPSPs evoked by stimulation of descending pathways. These results suggest that flexor, but not ankle extensor, group I afferent fibres can modulate sensory transmission at the synapse between Ia afferent fibres and Ia inhibitory interneurones. Conditioning stimulation of flexor muscle nerves, extensor muscle nerves and cutaneous nerves produced a long-lasting increase in excitability of the terminals of the Ia inhibitory interneurones. The increase in the excitability of the terminals was not secondary to an electrotonic spread of synaptic excitation at the soma. Indeed, concomitant with the excitability increase of the terminals there were signs of synaptic inhibition in the soma. The unitary IPSPs induced in target motoneurones following the spike activity of single Ia inhibitory interneurones were depressed by conditioning stimulation of muscle and cutaneous nerves. Since the conditioning stimulation also evoked compound IPSPs in those motoneurones, a firm conclusion as to whether unitary IPSP depression involved presynaptic inhibitory mechanism of the terminals of the interneurones could not be reached. The possibility that the changes in excitability of the Ia interneuronal terminals reflect the presence of a presynaptic inhibitory mechanism similar to that operating at the terminals of the afferent fibres (presynaptic inhibition) is discussed.1. In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. PMID:10922013

Assessing the neurotoxic effects of palytoxin and ouabain, both Na⁺/K⁺-ATPase inhibitors, on the myelinated sciatic nerve fibres of the mouse: an ex vivo electrophysiological study.

PubMed

Kagiava, Alexia; Aligizaki, Katerina; Katikou, Panagiota; Nikolaidis, Georgios; Theophilidis, George

2012-03-01

Palytoxin (PlTX) is a marine toxin originally isolated from the zoantharians of the genus Palythoa. It is considered to be one of the most lethal marine toxins that block the Na⁺/K⁺-ATPase. This study was designed to investigate the acute effects of PlTX and ouabain, also an Na⁺/K⁺-ATPase blocker, on the mammalian peripheral nervous system using an ex vivo electrophysiological preparation: the isolated mouse sciatic nerve. Amplitude of the evoked nerve compound action potential (nCAP) was used to measure the proper functioning of the sciatic nerve fibres. The half-vitality time of the nerve fibres (the time required to inhibit the nCAP to 50% of its initial value: IT₅₀) incubated in normal saline was 24.5 ± 0.40 h (n = 5). Nerves incubated continuously in 50.0, 10.0, 1.0, 0.5, 0.250 and 0.125 nM of PlTX had an IT₅₀ of 0.06 ± 0.00, 0.51 ± 0.00, 2.1 ± 0.10, 8.9 ± 0.30, 15.1 ± 0.30 h, and 19.5 ± 0.20 h, respectively (n = 5, 3, 4, 4, 10). PlTX was extremely toxic to the sciatic nerve fibres, with a minimum effective concentration (mEC) of 0.125 nM (n = 5) and inhibitory concentration to 50% (IC₅₀) of 0.32 ± 0.08 nM (incubation time 24 h). Ouabain was far less toxic, with a mEC of 250.0 μM (n = 5) and IC₅₀ of 370.0 ± 18.00 μM (incubation 24.5 h). Finally, when the two compounds were combined--e.g. pre-incubation of the nerve fibre in 250.0 μM ouabain for 1 h and then exposure to 1.0 nM PlTX--ouabain offered minor a neuroprotection of 9.1-17.6% against PlTX-induced neurotoxicity. Higher concentrations of ouabain (500.0 μM) offered no protection. The mouse sciatic nerve preparation is a simple and low-cost bioassay that can be used to assess and quantify the neurotoxic effects of standard PlTX or PlTX-like compounds, since it appears to have the same sensitivity as the haemolysis of erythrocytes assay--the standard ex vivo test for PlTX toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Massive nerve root enlargement in chronic inflammatory demyelinating polyneuropathy.

PubMed Central

Schady, W; Goulding, P J; Lecky, B R; King, R H; Smith, C M

1996-01-01

OBJECTIVE: To report three patients with chronic inflammatory demyelinating polyneuropathy (CIDP) presenting with symptoms suggestive of cervical (one patient) and lumbar root disease. METHODS: Nerve conduction studies, EMG, and nerve biopsy were carried out, having found the nerve roots to be very enlarged on MRI, CT myelography, and at surgery. RESULTS: Clinically, peripheral nerve thickening was slight or absent. Subsequently one patient developed facial nerve hypertrophy. This was mistaken for an inner ear tumour and biopsied, with consequent facial palsy. Neurophysiological tests suggested a demyelinating polyneuropathy. Sural nerve biopsy showed in all cases some loss of myelinated fibres, inflammatory cell infiltration, and a few onion bulbs. Hypertrophic changes were much more prominent on posterior nerve root biopsy in one patient: many fibres were surrounded by several layers of Schwann cell cytoplasm. There was an excellent response to steroids in two patients but not in the third (most advanced) patient, who has benefited only marginally from intravenous immunoglobulin therapy. CONCLUSIONS: MRI of the cauda equina may be a useful adjunct in the diagnosis of CIDP. Images PMID:8971116

In vivo three-dimensional confocal laser scanning microscopy of the epithelial nerve structure in the human cornea.

PubMed

Stachs, Oliver; Zhivov, Andrey; Kraak, Robert; Stave, Joachim; Guthoff, Rudolf

2007-04-01

Evaluation of a new method for in vivo visualization of the distribution and morphology of human anterior corneal nerves. The anterior cornea was examined to a depth of 100 microm in four human volunteers with a confocal laser scanning microscope (CLSM) using a Rostock Cornea Module (developed in house) attached to a Heidelberg Retina Tomograph II (Heidelberg Engineering, Germany). Optical sections were digitally reconstructed in 3D using AMIRA (TGS Inc., USA). The scanned volumes had a greatest size of 300 x 300 x 40 microm and voxel size of 0.78 x 0.78 x 0.95 microm. The spatial arrangement of the epithelium, nerves and keratocytes was visualized by in vivo 3D-CLSM. The 3D-reconstruction of the volunteers' corneas in combination with the oblique sections gave a picture of the nerves in the central human cornea. Thin nerves run in the subepithelial plexus aligned parallel to Bowman's layer and are partially interconnected. The diameter of these fibres varied between 1.0 and 5 microm. Thick fibres rose out of the deeper stroma. The diameter of the main nerve trunks was 12+/-2 microm. Branches penetrating the anterior epithelial cell layer could not be visualized. 3D-CLSM allows analysis of the spatial arrangement of the anterior corneal nerves and visualization of the epithelium and keratocytes in the living human cornea. The developed method provides a basis for further studies of alterations of the cellular arrangement and epithelial innervation in corneal disease. This may help to clarify alterations of nerve fibre patterns under various clinical and experimental conditions.

Uncultured undifferentiated adipose-derived nucleated cell fractions combined with inside-out artery graft accelerate sciatic nerve regeneration and functional recovery.

PubMed

Mohammadi, R; Asadollahi, A; Amini, K

2014-09-01

Effects of transplantation of adipose-derived nucleated cell fractions (ADNCs) on sciatic nerve regeneration were studied. A 10-mm sciatic nerve defect was bridged using artery graft filled with ADNCs. In control group, artery graft was filled with saline alone. Regenerated nerve fibres were studied for 12 weeks. In sham-operated group, sciatic nerve was only exposed and manipulated. Behavioural and functional studies confirmed faster recovery of regenerated axons in ADNCs transplanted animals than in control group (P<0.05). At the end of study period, animals in ADNCs transplanted group achieved a sciatic functional index (SFI) value of -31.6 ± -3.14, whereas in control group a value of -42.5 ± -3.7 was found. Gastrocnemius muscle mass in ADNCs transplanted animals was found to be significantly higher than that in control group (P=0.001). Morphometric indices of regenerated fibres showed the number and diameter of myelinated fibres to be significantly higher in ADNCs transplanted animals than in control group (P=0.001). On immunohistochemistry, there was more positive staining of S100 in the ADNCs transplanted animals than in control group. ADNCs transplantation into an artery graft could be considered a readily accessible technique that improves functional recovery of sciatic nerve. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Objective perimetry using a four-channel multifocal VEP system: correlation with conventional perimetry and thickness of the retinal nerve fibre layer.

PubMed

Horn, Folkert K; Kaltwasser, Christoph; Jünemann, Anselm G; Kremers, Jan; Tornow, Ralf P

2012-04-01

There is evidence that multifocal visual evoked potentials (VEPs) can be used as an objective tool to detect visual field loss. The aim of this study was to correlate multifocal VEP amplitudes with standard perimetry data and retinal nerve fibre layer (RNFL) thickness. Multifocal VEP recordings were performed with a four-channel electrode array using 58 stimulus fields (pattern reversal dartboard). For each field, the recording from the channel with maximal signal-to-noise ratio (SNR) was retained, resulting in an SNR optimised virtual recording. Correlation with RNFL thickness, measured with spectral domain optical coherence tomography and with standard perimetry, was performed for nerve fibre bundle related areas. The mean amplitudes in nerve fibre related areas were smaller in glaucoma patients than in normal subjects. The differences between both groups were most significant in mid-peripheral areas. Amplitudes in these areas were significantly correlated with corresponding RNFL thickness (Spearman R=0.76) and with standard perimetry (R=0.71). The multifocal VEP amplitude was correlated with perimetric visual field data and the RNFL thickness of the corresponding regions. This method of SNR optimisation is useful for extracting data from recordings and may be appropriate for objective assessment of visual function at different locations. This study has been registered at http://www.clinicaltrials.gov (NCT00494923).

The LDIFLARE and CCM methods demonstrate early nerve fibre abnormalities in untreated hypothyroidism: a prospective study.

PubMed

Sharma, Sanjeev; Tobin, Victoria; Vas, Prashant R J; Rayman, Gerry

2018-05-31

Recent studies using skin biopsy suggest presence of small fibre neuropathy in subclinical hypothyroidism. This study uses two novel non-invasive methods - the Laser Doppler imager (LDIFLARE) and Corneal confocal microscopy (CCM) - to assess small fibre function (SFF) and structure (SFS) respectively in newly diagnosed hypothyroidism (HT) before and after adequate treatment. Single-center, prospective, intervention-based cohort study. 20 patients with newly diagnosed HT- 15 primary and 5 post-radioiodine - along with 20 age-matched healthy controls (HC). Both HT and HC were assessed neurologically at diagnosis and baseline respectively. The HT group was reassessed after optimal replacement (defined as TSH:0.27-4.20mIU/L) with levothyroxine (LT4) while HC were reviewed at 1-year interval. Neurological assessment for small fibres was performed using the LDIFLARE for SFF and CCM for SFS while large fibres were studied by sural nerve conduction velocity (SNCV) and amplitude (SNAP). At baseline, compared to HC, both LDIFLARE (mean±SD) (6.74±1.20vs.8.90±1.75cm2; p=0.0002) and CCM-nerve fibre density (CNFD) (50.77±6.54vs.58.32±6.54no/mm2;p=0.002) were significantly reduced in HT whereas neither SNCV nor SNAP were different (p=>0.05). Following optimal LT4 treatment, both LDIFLARE (7.72±1.12vs.6.74±1.20 cm2; p=<0.0001) and CNFD (54.43±5.70vs.50.77±6.54no/mm2; p=0.02) improved significantly but remained significantly reduced compared to HC (p=0.008 and p=0.01 respectively) despite normalization of TSH. This study demonstrates that dysfunction of small fibres precedes large neural fibres in early hypothyroidism. This can be reversed by replacement therapy to achieve a biochemically euthyroid state but small fibres neural outcomes continued to be remain low when compared to HC.

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.

A fine-structural survey of the pulpal innervation in the rat mandibular incisor.

PubMed

Bishop, M A

1981-02-01

The innervation of the rat incisor pulp has been studied using transmission electron microscopy and light microscopy. Transverse sections of mandibular incisor pulp (380-460 gm rats) from numerous positions in the long axis of the tooth were examined systematically in the electron microscopy. Quantitative data on total axon populations were obtained. The nerve fibers were found to pass through the lingual half of the pulp from the apical end to within 2 mm of the incisal tip. Although the nerve fibers were seen to lie amongst the connective tissue cells between the blood vessels, the electron microscopic observations showed that the blood vessels are not innervated. Throughout their pulpal course the nerve fibers showed no trace of perineurial investment. Virtually all the axons were unmyelinated. Total numbers of axons were small (233-328) and peak diameters of 0.3-0.4 microM confirmed the observed immature appearance of the nerve supply. Obvious nerve endings were seldom observed and the axons showed no structural association with odontoblasts. The evidence indicates that, although most axons terminate near the incisal end of the tooth, no specific structure is supplied. The qualitative features of the axons do not suggest autonomic function; however, they are consistent with a sensory role.

Why intra-epidermal electrical stimulation achieves stimulation of small fibres selectively: a simulation study

NASA Astrophysics Data System (ADS)

Motogi, Jun; Sugiyama, Yukiya; Laakso, Ilkka; Hirata, Akimasa; Inui, Koji; Tamura, Manabu; Muragaki, Yoshihiro

2016-06-01

The in situ electric field in the peripheral nerve of the skin is investigated to discuss the selective stimulation of nerve fibres. Coaxial planar electrodes with and without intra-epidermal needle tip were considered as electrodes of a stimulator. From electromagnetic analysis, the tip depth of the intra-epidermal electrode should be larger than the thickness of the stratum corneum, the electrical conductivity of which is much lower than the remaining tissue. The effect of different radii of the outer ring electrode on the in situ electric field is marginal. The minimum threshold in situ electric field (rheobase) for free nerve endings is estimated to be 6.3 kV m-1. The possible volume for electrostimulation, which can be obtained from the in situ electric field distribution, becomes deeper and narrower with increasing needle depth, suggesting that possible stimulation sites may be controlled by changing the needle depth. The injection current amplitude should be adjusted when changing the needle depth because the peak field strength also changes. This study shows that intra-epidermal electrical stimulation can achieve stimulation of small fibres selectively, because Aβ-, Aδ-, and C-fibre terminals are located at different depths in the skin.

Development of the peptidergic innervation of human heart.

PubMed Central

Gordon, L; Polak, J M; Moscoso, G J; Smith, A; Kuhn, D M; Wharton, J

1993-01-01

The aim of the present investigation was to study the developing peptidergic innervation of the human fetal heart of 7-24 wk gestational age. An immunohistochemical approach was adopted and the total innervation visualised with antisera to general neuronal and Schwann cell markers, while the onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP). Cardiac ganglia and nerves were demonstrated from 7 wk of gestation whereas peptide-immunoreactive nerves were not observed until the 10th week of gestation. NPY-immunoreactive nerve fibres constituted the major subpopulation of peptide-containing nerves identified in the fetal heart, exhibiting a descending atrial to ventricular density gradient, and were first identified during the 10th wk of gestation. Somatostatin- and VIP-immunoreactive nerves appeared at 10-12 wk of gestation and were mainly distributed in the atria. Somatostatin immunoreactivity was localised to cell bodies in cardiac ganglia, as well as to nerve fibres, indicating an intrinsic origin for this nerve subpopulation. Conversely, the other peptide-containing nerves appear to be of extrinsic origin, including those immunoreactive for VIP. Intracardiac neurons exhibit a transient expression of tyrosine hydroxylase immunoreactivity. Putative sympathetic nerve fibres, displaying tyrosine hydroxylase and NPY immunoreactivity, were demonstrated before the adrenergic innervation has previously been shown to be present by formaldehyde-induced fluorescence staining of catecholamines. The onset of the CGRP- and SP-immunoreactive innervation, at 18-24 wk of gestation, followed the appearance of other peptide-containing nerves, suggesting that the sensory, afferent innervation occurs later than the autonomic. The differential appearance and distribution of peptide-containing nerve subpopulations indicate that there is a chronological order to the development of the autonomic and sensory components of human cardiac innervation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:7505778

Sensory innervation of the temporomandibular joint in the mouse.

PubMed

Dreessen, D; Halata, Z; Strasmann, T

1990-01-01

The sensory innervation of the temporomandibular joints (TMJs) of 8 STR/IN mice was investigated by means of light and electron microscopy. Through the cutting of complete semithin sections in series it was possible to investigate the joints thoroughly. Additionally, one joint with its nerve supply was reconstructed three-dimensionally with a computerized three-dimensional programme. The reconstruction was based on one complete semithin section series. The joint's nerve supply originates from the nervus auriculotemporalis and additionally from motor branches of the n. mandibularis: n. massetericus, n. pterygoideus lateralis and the nn. temporales posteriores. The greatest number of nerve fibres and endings is located in the dorsolateral part of the joint capsule. They lie only in the stratum fibrosum and subsynovially. Neither the stratum synoviale nor the discus articularis contain any nerve fibres or endings, whereas the peri-articular loose connective tissue is richly innervated. The only type of nerve ending observed within the joint was the free nerve ending, which is assumed to serve not only as a nociceptor but also as a polymodal mechanoreceptor. Merely within the insertion of the musculus pterygoideus lateralis at the collum mandibulae single stretch receptors of the Ruffini type were observed. Ultrastructurally, they correspond to those described in the cat's knee joint. Neither lamellated nor nerve endings of the Golgi or Pacini type were observed in the joint or in the peri-articular connective tissue. The unexpected paucity of nerve fibres and endings in the TMJ itself of the mouse suggests that the afferent information from the joint is less important for position sense and movement than the afferent information from muscles, tendons and periodontal ligaments.

Postnatal development of the myenteric plexus in cat stomach.

PubMed

Lolova, I; Itsev, D

1983-01-01

The postnatal development of the myenteric plexus in cat stomach has been studied at birth, on the 14th, 30th, 45th and 180th postnatal days, using light- and electronmicroscopic methods. In newborn kittens the main network of the Auerbach plexus is well formed, but the myenteric ganglia are composed of nerve cells with different maturity and a scarce neuropile. During the first two postnatal weeks the dimensions of the ganglia increase owing to the increase of the nerve bodies and the rising number of glials cells and intercellular fibres. This is accompanied by a potentiation of the AChE-activity, mainly in the nerve cell bodies and to a lesser extent in the neuropile. Impregnation reveals different in calibre and form nerve fibres and terminals. Different ultrastructural types of neurones are identified on the 14th day. Later development is expressed in the formation of large compact ganglia and thick connecting strands. The number of AChE-positive fibres in the neuropile increases. Owing to the increase in the cell organelles and their more advanced maturity, it is possible to define the ultrastructural type of an ever increasing number of neurones.

An intracellular characterization of neurones and neural connexions within the left coeliac ganglion of cats.

PubMed Central

Decktor, D L; Weems, W A

1983-01-01

Intracellular recordings were made in vitro from neurones located within the left coeliac ganglion of the cat solar plexus. Thirty percent of the neurones within left coeliac ganglia were identified as efferent neurones. Within this neuronal population, splenic-efferent and renal-efferent neurones were identified specifically. Neurones within left coeliac ganglia were characterized as either phasic (fast adapting) neurones or tonic (slowly adapting) neurones depending upon their prolonged firing behaviour. Electrophysiological properties of neurones varied considerably. The wide range of values obtained for both input resistance and input capacitance suggest that sizeable differences in either specific membrane resistance or cell geometry exist within the over-all neurone population. Frequency distributions of input resistance, time constant, input capacitance and current threshold for tonic and phasic neurones were found to be significantly different. Compound excitatory post-synaptic potentials were produced by stimulation of the ipsilateral splanchnic nerves in 69% of the neurones tested and in 3% of the neurones tested upon stimulation of the contralateral splanchnic nerves. Electrical stimulation of nerve fibres located in the coeliac plexus, the superior mesenteric plexus or the left renal nerves generated excitatory synaptic potentials in neurones located within left coeliac ganglia. It is concluded that neurones within the left coeliac ganglion are innervated by splanchnic nerve fibres primarily contained within the left splanchnic nerves, receive excitatory synaptic input from splenic, renal and other peripheral preganglionic fibres and have extremely varied electrophysiological properties. PMID:6620179

Reflexive contraction of the levator palpebrae superioris muscle to involuntarily sustain the effective eyelid retraction through the transverse trigeminal proprioceptive nerve on the proximal Mueller's muscle: verification with evoked electromyography.

PubMed

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

2010-01-01

We have proposed a hypothetical mechanism to involuntarily sustain the effective eyelid retraction, which consists of not only voluntary but also reflexive contractions of the levator palpebrae superior muscle (LPSM). Voluntary contraction of fast-twitch fibres of the LPSM stretches the mechanoreceptors in Mueller's muscle to evoke trigeminal proprioception, which induces continuous reflexive contraction of slow-twitch fibres of the LPSM through the trigeminal proprioceptive nerve fibres innervating the mechanoreceptors in Mueller's muscle via the oculomotor neurons, as a tonic trigemino-oculomotor reflex. In the common skeletal mixed muscles, electrical stimulation of the proprioceptive nerve, which apparently connects the mechanoreceptors in muscle spindles to the motoneurons, induces the electromyographic response as the Hoffmann reflex. To verify the presence of the trigemino-oculomotor reflex, we confirmed whether intra-operative electrical simulation of the transverse trigeminal proprioceptive nerve on the proximal Mueller's muscle evokes an electromyographic response in the LPSM under general anaesthesia in 12 patients. An ipsilateral, phasic, short-latency response (latency: 2.8+/-0.3 ms) was induced in the ipsilateral LPSM in 10 of 12 subjects. As successful induction of the short-latency response in the ipsilateral LPSM corresponds to the Hoffmann reflex in the common skeletal mixed muscles, the present study is the first electromyographic verification of the presence of the monosynaptic trigemino-oculomotor reflex to induce reflexive contraction of the LPSM. The presence of the trigemino-oculomotor reflex may elucidate the unexplainable blepharoptosis due to surgery, trauma and tumour, all of which may damage the trigeminal proprioceptive nerve fibres to impair the trigemino-oculomotor reflex. Copyright (c) 2008. Published by Elsevier Ltd.

Phrenic motor outputs in response to bronchopulmonary C‐fibre activation following chronic cervical spinal cord injury

PubMed Central

2016-01-01

Key points Activation of bronchopulmonary C‐fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity.Following chronic cervical spinal cord injury, bronchopulmonary C‐fibre activation‐induced inhibition of phrenic activity was exaggerated.Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C‐fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord‐injured animals.These data suggest that activation of bronchopulmonary C‐fibres may retard phrenic output recovery following cervical spinal cord injury.The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Abstract Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin‐induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8–9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra‐jugular capsaicin (1.5 μg kg−1) injection was performed to activate the bronchopulmonary C‐fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin‐induced prolongation of expiratory duration was significantly attenuated in C2Hx animals. However, ipsilateral phrenic activity was robustly reduced after capsaicin treatment compared to uninjured animals. Single phrenic fibre recording experiments demonstrated that C2Hx animals had a higher proportion of late‐inspiratory phrenic motoneurons that were relatively sensitive to capsaicin treatment compared to early‐inspiratory phrenic motoneurons. Moreover, late‐inspiratory phrenic motoneurons in C2Hx animals had a weaker discharge frequency and slower recovery time than uninjured animals. These results suggest bilateral phrenic nerves differentially respond to bronchopulmonary C‐fibre activation following unilateral cervical hemisection, and the severe inhibition of phrenic bursting is due to a shift in the discharge pattern of phrenic motoneurons. PMID:27106483

[Changes in the innervation of the taste buds in diabetic rats].

PubMed

Hevér, Helén; Altdorfer, Károly; Zelles, Tivadar; Batbayar, Bayarchimeg; Fehér, Erzsébet

2013-03-24

Abnormal sensations such as pain and impairment of taste are symptoms of approximately 10% of patients having diabetes mellitus. The aim of the study was to investigate and quantify the different neuropeptide containing nerve fibres in the vallate papilla of the diabetic rat. Immunohistochemical methods were used to study the changes of the number of different neuropeptide containing nerve terminals located in the vallate papillae in diabetic rats. Diabetes was induced in the rats with streptozotocin. Two weeks after streptozotocin treatment the number of the substance P, galanin, vasoactive intestinal polypeptide and neuropeptide Y immunoreactive nerve terminals was significantly increased (p<0.05) in the tunica mucosa of the tongue. The number of the lymphocytes and mast cells was also increased significantly. Some of the immunoreactive nerve terminals were located in the lingual epithelium both intragemmally and extragemmally and were seen to comprise dense bundles in the lamina propria just beneath the epithelium. No taste cells were immunoreactive for any of the investigated peptides. Vasoactive intestinal polypeptide and neuropeptide Y immunoreactive nerve fibres were not detected in the taste buds. For weeks after streptozotocin administration the number of the substance P, calcitonin gene related peptide and galanin immunoreactive nerve terminals was decreased both intragemmally and intergemmally. In case of immediate insulin treatment, the number of the immunoreactive nerve terminals was similar to that of the controls, however, insulin treatment given 1 week later to diabetic rats produced a decreased number of nerve fibers. Morphometry revealed no significant difference in papilla size between the control and diabetic groups, but there were fewer taste buds (per papilla). Increased number of immunoreactive nerve terminals and mast cells 2 weeks after the development of diabetes was the consequence of neurogenic inflammation which might cause vasoconstriction and lesions of the oral mucosa. Taste impairment, which developed 4 weeks after streptozotocin treatment could be caused by neuropathic defects and degeneration or morphological changes in the taste buds and nerve fibres.

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.

Ultrastructure of free-ending nerve fibres in oesophageal epithelium.

PubMed Central

Robles-Chillida, E M; Rodrigo, J; Mayo, I; Arnedo, A; Gómez, A

1981-01-01

For the first time, at the ultrastructural level, the existence of free-ending, intraepithelial nerve fibres has been demonstrated in the oesophagus wall of adult cats and monkeys. Their form, the way they penetrate the epithelium, their location within the epithelium and their relationships with neighbouring cells have been established. A sensory function is suggested for this type of ending. Images Figs. 1-4 Figs. 5-6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Figs. 14-15 Figs. 16-17 PMID:7333951

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.

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

PubMed Central

Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

2011-01-01

The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MDC1A. We found that, compared with wild-type, sciatic nerves of Lama2−/− mice had a significant increase in both proliferating (Ki67+) cells and premyelinating (Oct6+) Schwann cells, but also had a significant decrease in both immature/non-myelinating [glial fibrillary acidic protein (GFAP)+] and myelinating (Krox20+) Schwann cells. To extend our previous work in which we found that doxycycline, which has multiple effects on mammalian cells, improves motor behavior and more than doubles the median life-span of Lama2−/− mice, we also determined how nerve pathology was affected by doxycycline treatment. We found that myelinating (Krox20+) Schwann cells were significantly increased in doxycycline-treated compared with untreated sciatic nerves. In addition, doxycycline-treated peripheral nerves had significantly less pathology as measured by assays such as amount of unmyelinated or disorganized axons. This study thus identified aberrant proliferation and differentiation of Schwann cells as key components of pathogenesis in peripheral nerves and provided proof-of-concept that pharmaceutical therapy can be of potential benefit for peripheral nerve dysfunction in MDC1A. PMID:21505075

A photon-driven micromotor can direct nerve fibre growth

NASA Astrophysics Data System (ADS)

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

2012-01-01

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

Development of peptide-containing nerves in the human fetal prostate gland.

PubMed

Jen, P Y; Dixon, J S

1995-08-01

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l-ENK-IR nerves together with a few m-ENK-IR nerves. Occasional smooth muscle-associated varicose nerve fibres showed immunoreactivity for SP, CGRP, VIP or BOM although the majority of these types of nerve formed perivascular plexuses. Also at 26 wk numerous varicose nerve fibres were observed in association with the prostatic acini, the majority of such nerves containing NPY with a few showing immunoreactivity to VIP, l-ENK, SP or CGRP.(ABSTRACT TRUNCATED AT 400 WORDS)

Nervous system immunohistochemistry of the parasitic cnidarian Polypodium hydriforme at its free-living stage.

PubMed

Raikova, Ekaterina V; Raikova, Olga I

2016-04-01

Polypodium hydriforme, the only species in Polypodiozoa, which is currently considered a class of Cnidaria, and likely a sister group to Medusozoa (together with Myxozoa), is a cnidarian adapted to intracellular parasitism inside sturgeon oocytes. Free-living P. hydriforme lives on river bottoms; it walks on supporting tentacles and uses sensory tentacles to capture food and bring it to the mouth. The nervous system of free-living P. hydriforme was studied by confocal microscopy and immunohistochemistry using antibodies to FMRF-amide and α-tubulin combined with phalloidin-staining of F-actin fibres. A sensory FMRF-amide immunoreactive (IR) nerve net and an α-tubulin IR nerve net have been identified. The FMRF-amide IR nerve net underlies the epidermis along the tentacles and around the mouth; it consists of neurites emanating from epidermal sensory cells and basiepidermal ganglion cells, and it connects with cnidocytes. A deeper-lying α-tubulin IR nerve net occurs only in tentacles and looks like chains of different-sized beads crossing the mesoglea and entwining muscles. Anti-α-tubulin staining also reveals microtubules in muscle cells following the longitudinal muscle fibres or the thin circular F-actin fibres of the tentacles. Cnidocytes in the tentacles are embedded in a regular hexagonal non-neural network formed by the tubulin IR cytoskeleton of epidermal cells. Cnidocils of the cnidocytes around the mouth and in walking tentacles are identical, but those in sensory tentacles differ in length and width. The possible homology of the tubulin IR nerve net with motor nerve nets of cnidarians is discussed. The absence of a classic nerve ring around the mouth and the lack of specialised sense organs are considered to be plesiomorphic characters for Cnidaria. Copyright © 2015 Elsevier GmbH. All rights reserved.

Pressure wave injuries to the nervous system caused by high-energy missile extremity impact: Part I. Local and distant effects on the peripheral nervous system--a light and electron microscopic study on pigs.

PubMed

Suneson, A; Hansson, H A; Seeman, T

1990-03-01

Pigs were used for studies of effects on the peripheral nervous tissue of pressure waves induced by impact and passage through the left thigh of high-energy missiles. The short-lasting pressure waves were demonstrated to move close to the speed of sound and to have a spectrum of high frequencies and large amplitudes. The sciatic nerve in the contralateral leg showed no hemorrhage or major deformation. Both immediately after the missile impact and after 48 hr the myelin sheaths in the contralateral sciatic nerve showed deformation. Myelin was bulging into the axon, dislocating the axoplasm. The nodes of Ranvier could be exposed to an increased extent. Electron microscopic examination revealed decreased number of microtubules immediately after the trauma, persisting even after 48 hr in the largest axon. Schwann cells showed, especially after 48 hr, signs of damage and swelling. Similar changes, although less extensive, were noticed in the phrenic nerves as well as in unmyelinated axons in both sciatic and phrenic nerves. It is concluded that a high-energy missile hit in the thigh of a pig, caused structurally demonstrable dislocations of myelin sheaths, and disarrangement of cytoskeleton and endoplasmic reticulum in axons as well as other signs of damage. The changes may interfere with the normal functions of peripheral and autonomic nerves.

Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head

PubMed Central

Jones, H. J.; Girard, M. J.; White, N.; Fautsch, M. P.; Morgan, J. E.; Ethier, C. R.; Albon, J.

2015-01-01

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse. PMID:25808336

Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head.

PubMed

Jones, H J; Girard, M J; White, N; Fautsch, M P; Morgan, J E; Ethier, C R; Albon, J

2015-05-06

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal-temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior-temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.

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

Differences in muscle sympathetic nerve response to isometric exercise in different muscle groups.

PubMed

Saito, M

1995-01-01

The aim of this study was to examine the effects of muscle fibre composition on muscle sympathetic nerve activity (MSNA) in response to isometric exercise. The MSNA, recorded from the tibial nerve by a microneurographic technique during contraction and following arterial occlusion, was compared in three different muscle groups: the forearm (handgrip), anterior tibialis (foot dorsal contraction), and soleus muscles (foot plantar contraction) contracted separately at intensities of 20%, 33% and 50% of the maximal voluntary force. The increases in MSNA relative to control levels during contraction and occlusion were significant at all contracting forces for handgrip and at 33% and 50% of maximal for dorsal contraction, but there were no significant changes, except during exercise at 50%, for plantar contraction. The size of the MSNA response correlated with the contraction force in all muscle groups. Pooling data for all contraction forces, there were different MSNA responses among muscle groups in contraction forces (P = 0.0001, two-way analysis of variance), and occlusion periods (P = 0.0001). The MSNA increases were in the following order of magnitude: handgrip, dorsal, and plantar contractions. The order of the fibre type composition in these three muscles is from equal numbers of types I and II fibres in the forearm to increasing number of type I fibres in the leg muscles. The different MSNA responses to the contraction of different muscle groups observed may have been due in part to muscle metaboreflex intensity influenced by their metabolic capacity which is related to by their metabolic capacity which is related to the fibre type.

After facial nerve damage, regenerating axons become aberrant throughout the length of the nerve and not only at the site of the lesion: an experimental study.

PubMed

Choi, D; Raisman, G

2004-02-01

After facial nerve trauma, aberrant regeneration is associated with synkinesis. Animal models of mechanical nerve guides or reparative cell transplants at the site of a lesion have not been shown to improve disorganized regeneration. We examined whether this is because regenerating axons become disorganized throughout the length of the nerve and not only at the site of the lesion. In rats (n = 12), retrograde fluorescent tracer techniques were used to establish that most of the temporal branch fibres were carried in the superior half of the facial nerve trunk. In two further groups of rats (n = 24) a complete proximal facial nerve lesion was made, and the nerve immediately repaired by suture. After 4 weeks, at a second operation, the superior half of the facial nerve trunk was cut, either proximal or distal to the original lesion, and retrograde tracers were applied to distal branches of the nerve. It was possible to localize the points at which regenerating fibres became aberrant in their course by studying the number of labelled motoneurons in the facial nucleus after application of the tracer to the temporal branch of the nerve: this was similar in the distal and proximal hemisection groups, suggesting that aberrant axonal development occurred throughout the length of the nerve. Future strategies aimed at improving the organization of regeneration need to provide guidance cues not only at the site of the lesion as previously thought, but also throughout the length of the nerve.

Enkephalin-like immunoreactive principal ganglion cells and nerve fibres in the inferior mesenteric ganglion of the cat.

PubMed

Balayadi, M; Jule, Y; Cupo, A

1988-10-05

The occurrence and distribution of methionine-enkephalin (ME), leucine-enkephalin (LE) and methionine-enkephalin-Arg6-Gly7-Leu8 (MERGL)-like (LI) immunoreactive material in the inferior mesenteric ganglion (IMG) of the cat were studied by immunohistochemical techniques using the peroxidase-antiperoxidase method. Numerous ME-Li, LE-Li and MERGL-Li immunoreactive fibres with the same distribution pattern were observed. They were varicose and often surrounded closely neighbouring unlabelled ganglion cell bodies. Sometimes they ran in strands between ganglion cells. ME-Li immunoreactive material was detected in a number of cell bodies, the diameter of which was similar to that of unlabelled principal ganglion cell bodies, and which were probably Enk-Li-containing principal ganglion cells. These immunoreactive cells were often surrounded by ME-Li immunoreactive fibres. No LE-Li or MERGL-Li immunoreactive ganglion cell bodies were observed. The presence of ME-Li immunoreactive principal ganglion cells raises the possibility that the Enk-Li immunoreactive fibres present in the IMG may have a prevertebral ganglionic source. The possibility that the Enk-Li material present in nerve fibres might be derived from preproenkephalin-A was suggested by the occurrence of MERGL-Li immunoreactivity.

Peripheral nerve recruitment curve using near-infrared stimulation

NASA Astrophysics Data System (ADS)

Dautrebande, Marie; Doguet, Pascal; Gorza, Simon-Pierre; Delbeke, Jean; Nonclercq, Antoine

2018-02-01

In the context of near-infrared neurostimulation, we report on an experimental hybrid electrode allowing for simultaneous photonic or electrical neurostimulation and for electrical recording of evoked action potentials. The electrode includes three contacts and one optrode. The optrode is an opening in the cuff through which the tip of an optical fibre is held close to the epineurium. Two contacts provide action potential recording. The remaining contact, together with a remote subcutaneous electrode, is used for electric stimulation which allows periodical assessment of the viability of the nerve during the experiment. A 1470 nm light source was used to stimulate a mouse sciatic nerve. Neural action potentials were not successfully recorded because of the electrical noise so muscular activity was used to reflect the motor fibres stimulation. A recruitment curve was obtained by stimulating with photonic pulses of same power and increasing duration and recording the evoked muscular action potentials. Motor fibres can be recruited with radiant exposures between 0.05 and 0.23 J/cm2 for pulses in the 100 to 500 μs range. Successful stimulation at short duration and at a commercial wavelength is encouraging in the prospect of miniaturisation and practical applications. Motor fibres recruitment curve is a first step in an ongoing research work. Neural action potential acquisition will be improved, with aim to shed light on the mechanism of action potential initiation under photonic stimulation.

Morphological and functional differences between normal-tension and high-tension glaucoma.

PubMed

Häntzschel, Janek; Terai, Naim; Sorgenfrei, Friederike; Haustein, Michael; Pillunat, Karin; Pillunat, Lutz E

2013-08-01

To compare visual field (VF) and nerve fibre loss in patients with normal-tension (NTG) and high-tension glaucoma (HTG) at an equal level of glaucomatous structural damage of the optic nerve head (ONH). In a retrospective, pair-matched, comparative study, 126 eyes with NTG and 126 eyes with HTG were matched according to the same glaucomatous ONH damage based on rim volume, rim area and disc size measured by the Heidelberg Retina Tomograph (HRT III). Visual field by Humphrey perimetry and nerve fibre layer thickness measured by scanning laser polarimetry (GdxVCC) were compared between both groups. Based on the HRT, NTG and HTG displayed comparable structural damage of the ONH without a statistically significant difference between both groups (mean, NTG/HTG: disc area 2.32/2.32 mm², p =0.342; rim area 1.03/1.00 mm², p = 0.279; rim volume 0.2/0.19 mm³; p = 0.274). Eyes with NTG had significantly less VF damage than eyes with HTG (mean, NTG/HTG: mean deviation (MD) -3.69/-9.77 dB, p = 0.0001; pattern standard deviation (PSD) 4.80/7.17 dB, p = 0.0001). The nerve fibre layer of NTG patients was thicker than that of HTG patients (mean, NTG/HTG: GDx total: 46.9/44.0 μm, p = 0.073; GDx superior: 57.2/49.9 μm, p = 0.0001; GDx inferior: 54.9/49.7 μm, p = 0.001). At an equal level of glaucomatous structural damage of the ONH indicated by cupping, rim area and rim volume, NTG patients seem to have a less affected visual field and a better preserved nerve fibre layer than HTG patients. © 2013 The Authors. Acta Ophthalmologica © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by Blackwell Publishing Ltd.

The oculomotor system of decapod cephalopods: eye muscles, eye muscle nerves, and the oculomotor neurons in the central nervous system.

PubMed

Budelmann, B U; Young, J Z

1993-04-29

Fourteen extraocular eye muscles are described in the decapods Loligo and Sepioteuthis, and thirteen in Sepia; they are supplied by four eye muscle nerves. The main action of most of the muscles is a linear movement of the eyeball, only three muscles produce strong rotations. The arrangement, innervation and action of the decapod eye muscles are compared with those of the seven eye muscles and seven eye muscle nerves in Octopus. The extra muscles in decapods are attached to the anterior and superior faces of the eyes. At least, the anterior muscles, and presumably also the superior muscles, are concerned with convergent eye movements for binocular vision during fixation and capture of prey by the tentacles. The remaining muscles are rather similar in the two cephalopod groups. In decapods, the anterior muscles include conjunctive muscles; these cross the midline and each presumably moves both eyes at the same time during fixation. In the squids Loligo and Sepioteuthis there is an additional superior conjunctive muscle of perhaps similar function. Some of the anterior muscles are associated with a narrow moveable plate, the trochlear cartilage; it is attached to the eyeball by trochlear membranes. Centripetal cobalt fillings showed that all four eye muscle nerves have fibres that originate from somata in the ipsilateral anterior lateral pedal lobe, which is the oculomotor centre. The somata of the individual nerves show different but overlapping distributions. Bundles of small presumably afferent fibres were seen in two of the four nerves. They do not enter the anterior lateral pedal lobe but run to the ventral magnocellular lobe; some afferent fibres enter the brachio-palliovisceral connective and run perhaps as far as the palliovisceral lobe.

The effects of rearing light level and duration differences on the optic nerve, brain, and associated structures in developing zebrafish larvae: a light and transmission electron microscope study.

PubMed

Chapman, George B; Tarboush, Rania; Connaughton, Victoria P

2012-03-01

The ultrastructure of the optic nerve, brain, and some associated structures of larval zebrafish, grown under three different light regimens were studied. Fish grown under cyclic light (control), constant dark (CD), and constant light (CL) were studied for 4 and 8 days postfertilization (dpf). We also studied the control and CD fish at 15 dpf. The brains of the control and CL fish were larger at 4 dpf than at 8 dpf. In all 4 dpf fish, the brain occupied the entire expanse between the two retinas and the optic nerve extended the shortest distance between the retina and the brain. The 15 dpf zebrafish had the smallest brain size. Groups of skeletal muscle cells associated with the optic nerves became visible in all older larvae. In the 15 dpf larvae, bulges and dilations in the optic nerve occurred as it reached the brain and optic chiasms occurred proximal to the brain. Electron microscopy yielded information about myelinated and unmyelinated axons in the optic nerve, the dimensions of neurotubules, neurofilaments, and myofilaments, including a unique variation in actin myofilaments, and a confirmation of reported myosin myofilament changes (but with dimensions). We also describe the ultrastructure of a sheath-like structure that is confluent over the optic nerve and the brain, which has not been described before in zebrafish. Also presented are images of associated fibroblasts, epithelial cells lining the mouth, cartilage plates, blood vessels, nerve bundles, and skeletal muscle cells, most of which have not been previously described in the literature. Copyright © 2012 Wiley Periodicals, Inc.

Development of peptide-containing nerves in the human fetal prostate gland.

PubMed Central

Jen, P Y; Dixon, J S

1995-01-01

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l-ENK-IR nerves together with a few m-ENK-IR nerves. Occasional smooth muscle-associated varicose nerve fibres showed immunoreactivity for SP, CGRP, VIP or BOM although the majority of these types of nerve formed perivascular plexuses. Also at 26 wk numerous varicose nerve fibres were observed in association with the prostatic acini, the majority of such nerves containing NPY with a few showing immunoreactivity to VIP, l-ENK, SP or CGRP.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:7591978

Factors affecting finger and hand pain in workers with HAVS.

PubMed

House, R; Krajnak, K; Jiang, D

2016-06-01

Pain and its management are important aspects of hand-arm vibration syndrome (HAVS). To determine the factors associated with finger and hand pain in workers with HAVS and, specifically, to assess the impact of several neurological variables as well as the vascular component of HAVS, grip strength and age. We assessed men with HAVS at a hospital occupational medicine clinic over 2 years. Subjects scored finger and hand pain separately using the Borg Scale (0-10). The possible predictors we evaluated included the Stockholm Neurological Scale (SNS) and Stockholm Vascular Scale (SVS) stages, current perception threshold (CPT), carpal tunnel syndrome (CTS), ulnar neuropathy, grip strength and age. We carried out nerve conduction testing to confirm the presence of CTS and ulnar neuropathy and measured CPT in the fingers at 2000 Hz, 250 Hz and 5 Hz corresponding to A-beta (large myelinated), A-delta (small myelinated) and C (unmyelinated) fibres, respectively. We calculated Spearman rank correlations to examine the relation between finger and hand pain and possible predictor variables. Among the 134 subjects, the median (25th-75th percentile) pain scores were 6 (4-8) for the fingers and 5 (1-7) for the hands. We found statistically significant correlations with finger pain for the SVS stage (r = 0.239; P < 0.01) and CTS (r = 0.184; P < 0.05). The only statistically significant correlation identified for hand pain was a negative correlation with grip strength (r = -0.185; P < 0.05). Management of finger and hand pain in HAVS should focus on the correlates we have identified. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Components of action potential repolarization in cerebellar parallel fibres.

PubMed

Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

2014-11-15

Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

Focus on autonomic dysfunction in familial amyloidotic polyneuropathy (FAP).

PubMed

Obayashi, Konen; Ando, Yukio

2012-06-01

It is well known that autonomic dysfunction in familial amyloidotic polyneuropathy (FAP) is the most serious problem, because it restricts the daily life of these patients. The detail mechanisms of the onset are not well understood in FAP and domino liver transplantation-induced amyloid neuropathy. As autonomic disturbances play an important role in the symptomatology of FAP, further studies of autonomic dysfunction in these patients may lead the pathogenesis of FAP. Autonomic dysfunction is often observed before sensory and motor nerve dysfunction in FAP. This can be attributed to the morphological characteristics of the nerves. Unmyelinated, small myelinated, and large myelinated fibers tend to become impaired in that order. Although the reasons of susceptibility to amyloid infiltration and injury are not known, studies of autopsied FAP patients have revealed heavy infiltration of amyloid in autonomic ganglions. Moreover, spinal ganglion and posterior loot of the spine had severe amyloid deposits than did the anterior root of the spine or the motor nerves. It is well known that autonomic dysfunction is the most serious problem, because it restricts the daily life of FAP patients. However, we have four major questions about autonomic dysfunction in clinical. In this manuscript, we discuss about the answers of these questions.

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

PubMed

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

2003-07-01

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

[Acrodystrophic neuropathy in an alcoholic].

PubMed

Yamamura, Y; Hironaka, M; Shimoyama, M; Toyota, Y; Kurokawa, M; Kohriyama, T; Nakamura, S

1993-01-01

The patient was a 48-year-old alcoholic man with no contributory family history. At age 36 he had developed sensory dominant polyneuropathy with highly impaired temperature sensation and deep sensation in the lower extremities, recurrent ulcers of the toes, and sexual impotence. A sural nerve biopsy at this time revealed marked loss of myelinated fibers with relative preservation of the population of unmyelinated fibers. Subsequently, he developed muscle atrophy of the lower thighs, urinary incontinence, and Wernicke's encephalopathy, and became non-ambulatory at age 44. The peripheral nerve conduction findings suggested predominantly axonal degeneration. The entire course was characterized by alternative progression and partial recovery influenced by his alcohol intake and nutritional state. Alcoholic neuropathy is a major cause of solitary acrodystrophic neuropathy (ADN). Manifestations of autonomic and motor neuropathy are more marked in alcoholic ADN than in HSAN-I, and central nervous system involvement is the hallmark of alcoholic ADN. In the treatment of patients with alcoholic ADN, attention should be paid to diabetes mellitus, malnutritional state, and vitamin deficiency, which frequently complicate alcoholism.

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

PubMed

Sagara, M; Satoh, J; Wada, R; Yagihashi, S; Takahashi, K; Fukuzawa, M; Muto, G; Muto, Y; Toyota, T

1996-03-01

N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

Quantitative and qualitative morphology of rabbit retinal glia. A light microscopical study on cells both in situ and isolated by papaine.

PubMed

Reichenbach, A

1987-01-01

Rabbit retinal glia was studied by light microscopy of both stained sections of frozen retinae and enzymatically isolated cells. In the vast majority of this tissue, except for a small region around the optic nerve head, the glia consists solely of radial glia, i.e. Müller cells whose morphology was found to depend markedly on their topographic localization within the retina. Müller cells in the periphery are short and have thick vitreal processes bearing a single large endfoot. Central Müller cells are long and slender; through the thickening nerve fibre layer they send vitreal processes which are subdivided into several fine branches ending with multiple small endfeet. Müller cells in the retinal centre are far more closely packed than those in the periphery; everywhere, however, a constant ratio of Müller cells: neurons of about 1:15 was found, except for the juxta-optic nerve head region where this ratio is slightly reduced. Where the central retina reaches a thickness requiring Müller cell lengths of more than 130 micron, additional non-radial glial cells occur within the nerve fibre layer. The majority of these cells seem to be astrocytes. Their number per retinal area increases with the thickening of both the whole retina and the nerve fibre layer. The occurrence of these non-radial glial cells leads to an enhancement of the glia:neuron index in the retinal centre. Possible mechanisms of physiological control of gliogenesis are discussed.

Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in hairless mouse skin in vivo

PubMed Central

BUSSAU, L. J.; VO, L. T.; DELANEY, P. M.; PAPWORTH, G. D.; BARKLA, D. H.; KING, R. G.

1998-01-01

Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of the skin of hairless mice in vivo. Application of acridine orange enabled imaging of the layers of the epidermis. The corneocytes of the stratum corneum, the keratinocytes in the basal layers and redundant hair follicles were visualised at depths greater than 100 μm. Cellular and nuclear membranes of keratinocytes of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging of the skin after injection of FITC-dextran revealed an extensive network of blood vessels with a size range up to 20 μm. Blood cells could be seen moving through dermal vessels and the blood circulation through the dermal vascular bed was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves fibres around the hair follicles and subsurface blood vessels. Comparison was made between images obtained in vivo using FOCI and in vitro scanning electron microscopy and conventional histology. FOCI offers the potential to study dynamic events in vivo, such as blood flow, skin growth, nerve regeneration and many pathological processes, in ways which have not previously been possible. PMID:9643419

Intraepidermal nerve-fibre density as a biomarker of the course of neuropathy in patients with Type 2 diabetes mellitus.

PubMed

Divisova, S; Vlckova, E; Srotova, I; Kincova, S; Skorna, M; Dusek, L; Dubovy, P; Bednarik, J

2016-05-01

This paper aims to investigate whether intraepidermal nerve-fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type 2 diabetes mellitus. Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type 2 diabetes mellitus (median age 60 years, 17 men) with a short duration of diabetes (< 3 years) and good glucose control, and in 23 age- and sex-matched controls. The time intervals between biopsies were > 2 years (median 33.8 months). Eighteen patients with Type 2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy. At first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9 fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4 fibres/mm). The annual rate of intraepidermal nerve-fibre (IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean (se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P < 0.001] and similar to patients without polyneuropathy [12.16 (4.38)%]. The rate of IENF loss did not correlate with degree of glucose control. The annual rate of IENF loss in patients with Type 2 diabetes mellitus was several times higher than that of healthy participants, irrespective of the presence of signs or symptoms of diabetic polyneuropathy at initial evaluation. The change in IENFD is not linear and should be expressed as a proportion of initial IENFD to serve as a marker of the course of diabetic neuropathy. © 2015 Diabetes UK.

Development of sensory innervation in rat tibia: co-localization of CGRP and substance P with growth-associated protein 43 (GAP-43)

PubMed Central

Gajda, Mariusz; Litwin, Jan A; Cichocki, Tadeusz; Timmermans, Jean-Pierre; Adriaensen, Dirk

2005-01-01

The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16–21 and in neonates and juvenile individuals on postnatal days (PD) 1–28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes. PMID:16050900

[Met]- and [Leu]enkephalin-like immunoreactive cell bodies and nerve fibres in the coeliac ganglion of the cat.

PubMed

Julé, Y; Clerc, N; Niel, J P; Condamin, M

1986-06-01

The occurrence and distribution of methionine- and leucine-enkephalin-like immunoreactivity were investigated in the cat coeliac ganglion using either the indirect immunoperoxidase method or the peroxidase-antiperoxidase technique. Several antisera raised to methionine- and leucine-enkephalin were used. Their specificity was assessed by incubating sections of the coeliac ganglion with increasing dilutions of antisera and with antisera saturated with their respective antigen. The present study was performed both in untreated and in colchicine-treated cats. Immunoreactive methionine- and leucine-enkephalin-like cell bodies were only visualized in colchicine-treated cats. Two types of labeled cells were observed. The first type had a size similar to that of unlabeled principal ganglion cells. These labeled cells were numerous and scattered throughout the ganglion; they probably represented enkephalin-containing ganglion cells. The second type of immunoreactive cells were of a much smaller size. They were always gathered in small clusters of about 5-15 cells and were not numerous; they presumably represented enkephalin-containing small intensely fluorescent cells. Immunoreactive nerve fibres were mainly observed in untreated cats and accessorily in colchicine-treated cats. In untreated animals dense networks of methionine- and leucine-enkephalin-like immunoreactive fibres were found in the coeliac ganglion. These fibres had numerous varicosities which often closely surrounded unlabeled principal ganglion cells. In colchicine-treated cats some immunoreactive fibres surrounded labeled principal ganglion cell bodies. The present results establish for the first time the presence of enkephalin-like immunoreactive principal ganglion cells in a mammalian sympathetic prevertebral ganglion. The presence of enkephalin-containing principal ganglion cells, small intensely fluorescent cells and nerve terminals, supports an important role of enkephalins in the integrative synaptic activities of cat coeliac ganglion cells.

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

PubMed Central

Nishi, K.; Sakanashi, M.; Takenaka, F.

1974-01-01

1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

"Fast" and "slow" muscle fibres in hindlimb muscles of adult rats regenerate from intrinsically different satellite cells.

PubMed

Kalhovde, J M; Jerkovic, R; Sefland, I; Cordonnier, C; Calabria, E; Schiaffino, S; Lømo, T

2005-02-01

Myosin heavy chain (MyHC) expression was examined in regenerating fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of adult rats. Myotoxic bupivacaine was injected into SOL and EDL and the muscles were either denervated or neuromuscularly blocked by tetrodotoxin (TTX) on the sciatic nerve. Three to 10 or 30 days later, denervated SOL or EDL, or innervated but neuromuscularly blocked EDL received a slow 20 Hz stimulus pattern through electrodes implanted on the muscles or along the fibular nerve to EDL below the TTX block. In addition, denervated SOL and EDL received a fast 100 Hz stimulus pattern. Denervated EDL and SOL stimulated with the same slow stimulus pattern expressed different amounts of type 1 MyHC protein (8% versus 35% at 10 days, 13% versus 87% at 30 days). Stimulated denervated and stimulated innervated (TTX blocked) EDL expressed the same amounts of type 1, 2A, 2X and 2B MyHC proteins. Cross-sections treated for in situ hybridization and immunocytochemistry showed expression of type 1 MyHC in all SOL fibres but only in some scattered single or smaller groups of fibres in EDL. The results suggest that muscle fibres regenerate from intrinsically different satellite cells in EDL and SOL and within EDL. However, induction by different extrinsic factors arising in extracellular matrix or from muscle position and usage in the limb has not been excluded. No evidence for nerve-derived trophic influences was obtained.

Anatomical and neurohistological observations on the heart of the rose ringed parakeet, Psittacula krameri.

PubMed

Qayyum, M A; Shaad, F U

1976-01-01

Anatomy, histology and innervation of the heart of the rose ringed parakeet, Psittacula krameri have been studied in the present investigation. The sinuatrial node is found to be well-developed. It is located towards the right side of the cephalic end of the interatrial septum and composed of a few nucleated cells and a large fibrous mass. The atrioventricular node is poorly defined, present at the caudal end of the interatrial septum. The node is somewhat triangular in shape and is composed of elongated and multinucleated specialized fibres. The node is not covered by any connective tissue sheath. The poor development of the atrio ventricular node and the absence of any sheath around it may be correlated with the fast rate of the heart beat. The atrioventricular bundle is observed at the cephalic end of the interventricular septum. A branch from the right limb of the atrioventricular bundle is noted to pass directly into the right atrioventricular valve. The heart is richly innervated. Ganglion cells along with nerve fibres have been observed at the sulcus terminalis and the atrioventricular junction. A direct nervous connection could be observed between the sinuatrial and atrioventricular nodes. It is argued that the impulse which originates in the sinuatrial node would reach the atrioventricular node through the unspecialized muscle fibres and nerve fibres of the interatrial septum. Nerve cells could not be traced in the substance of the sinuatrial node, atrioventricular node and atrioventricular bundle.

Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow - Implication for treatment?

PubMed

Spang, C; Alfredson, H

2017-06-01

Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified. Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin and eosin, H and E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP). All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres. The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. IV.

Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow – Implication for treatment?

PubMed Central

Spang, C.; Alfredson, H.

2017-01-01

Background: Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified. Methods: Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin & eosin, H&E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP). Results: All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres. Conclusion: The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. Level of Evidence: IV. PMID:28574416

Combustion-derived nanoparticles, the neuroenteric system, cervical vagus, hyperphosphorylated alpha synuclein and tau in young Mexico City residents.

PubMed

Calderón-Garcidueñas, Lilian; Reynoso-Robles, Rafael; Pérez-Guillé, Beatriz; Mukherjee, Partha S; Gónzalez-Maciel, Angélica

2017-11-01

Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM 2.5 ), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls. Electron microscopy of epithelial, endothelial and neural cells and immunoreactivity of stomach and vagus to phosphorylated ɑ-synuclein Ser129 and Hyperphosphorylated-Tau (Htau) were evaluated and CDNPs measured in ENS. CDNPs were abundant in erythrocytes, unmyelinated submucosal, perivascular and intramuscular nerve fibers, ganglionic neurons and vagus nerves and associated with organelle pathology. ɑSyn and Htau were present in 25/27 MC gastric,15/26 vagus and 18/27 gastric and 2/26 vagus samples respectively. We strongly suggest CDNPs are penetrating and damaging the GI barrier and reaching preganglionic parasympathetic fibers and the vagus nerve. This work highlights the potential role of CDNPs in the neuroenteric hyperphosphorylated ɑ-Syn and tau pathology as seen in Parkinson and Alzheimer's diseases. Highly oxidative, ubiquitous CDNPs constitute a biologically plausible path into Parkinson's and Alzheimer's pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Electroneurographic findings in patients with solvent induced central nervous system dysfunction.

PubMed Central

Orbaek, P; Rosén, I; Svensson, K

1988-01-01

The function of the peripheral nervous system was examined in a group of 32 men aged 30-65 (mean 49) with diagnosed solvent induced chronic toxic encephalopathy. The subjects were examined at the time of diagnosis and 26 were re-examined after a follow up period of 22-72 months (mean 40) and compared with a group of 50 unexposed male workers aged 27-64 (mean 42) with appropriate adjustment for age. All subjects were carefully scrutinised for alcohol abuse and other neurological diseases. The results of motor fibre neurography disclosed no difference between the groups. Nevertheless, a significant decrease in motor conduction velocity was found in the patients at follow up. Sensory fibre neurography showed signs of slight axonal degeneration with significantly decreased sensory nerve action potential amplitudes in the median and sural nerves; these amplitudes increased during follow up. The duration of sensory nerve action potentials was longer in the exposed group for the median and the sural nerves. The percentage of late components was significantly higher in the median nerve. The warm-cold sensitivity in the exposed group also indicated a slight sensory dysfunction with statistically significant wider detection limits. PMID:2840109

Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study.

PubMed

Savini, G; Zanini, M; Carelli, V; Sadun, A A; Ross-Cisneros, F N; Barboni, P

2005-04-01

To investigate the correlation between retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) size in normal white subjects by means of optical coherence tomography (OCT). 54 eyes of 54 healthy subjects aged between 15 and 54 underwent peripapillary RNFL thickness measurement by a series of three circular scans with a 3.4 mm diameter (Stratus OCT, RNFL Thickness 3.4 acquisition protocol). ONH analysis was performed by means of six radial scans centred on the optic disc (Stratus OCT, Fast Optic Disc acquisition protocol). The mean RNFL values were correlated with the data obtained by ONH analysis. The superior, nasal, and inferior quadrant RNFL thickness showed a significant correlation with the optic disc area (R = 0.3822, p = 0.0043), (R = 0.3024, p = 0.026), (R = 0.4048, p = 0.0024) and the horizontal disc diameter (R = 0.2971, p = 0.0291), (R = 0.2752, p = 0.044), (R = 0.3970, p = 0.003). The superior and inferior quadrant RNFL thickness was also positively correlated with the vertical disc diameter (R = 0.3774, p = 0.0049), (R = 0.2793, p = 0.0408). A significant correlation was observed between the 360 degrees average RNFL thickness and the optic disc area and the vertical and horizontal disc diameters of the ONH (R = 0.4985, p = 0.0001), (R = 0.4454, p = 0.0007), (R = 0.4301, p = 0.0012). RNFL thickness measurements obtained by Stratus OCT increased significantly with an increase in optic disc size. It is not clear if eyes with large ONHs show a thicker RNFL as a result of an increased amount of nerve fibres or to the shorter distance between the circular scan and the optic disc edge.

The development of the experimental setup for measuring the cell membrane electrical potential by Sucrose-Gap Technique

NASA Astrophysics Data System (ADS)

Yuzhakov, AD; Nosarev, AV; Aleinik, AN

2017-11-01

This article describes the development of the experimental setup for measuring the cell membrane electrical potential by Double -Sucrose-Gap Technique. The double-gap isolation method allows the simultaneous measurement of electrical activity and tension output from contracting segments of muscle fibers. This technique has been widely used as a convenient tool for recording of the membrane activities from myelinated or unmyelinated nerves and muscle preparations. This device can be an effective way to provide undergraduate biomedical engineering students with invaluable experiences in neurophysiology. The installation design and its main characteristics are described. The advantages of the described device are the simplicity of the experiment, relatively low cost, the possibility of long-term experiment.

Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes.

PubMed

Duggan, A W; Schaible, H G; Hope, P J; Lang, C W

1992-05-08

Antibody microprobes bearing antibodies to the C-terminus of substance P (SP) were used to measure release of immunoreactive (ir) SP in the dorsal horn of barbiturate anaesthetized spinal cats. Electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve produced a relatively localised release of ir SP in the superficial dorsal horn. Prior microinjection of the peptidase inhibitors kelatorphan and enalaprilat in the dorsal horn resulted in ir SP being detected over the whole of the dorsal horn and the overlying dorsal column. This pattern had previously been observed with evoked release of ir neurokinin A and supports the proposal that a slow degradation results in a neuropeptide accessing many sites remote from sites of release.

The syndrome of `continuous muscle-fibre activity' cured: further studies

PubMed Central

Isaacs, Hyam; Heffron, J. J. A.

1974-01-01

Two cases suffering from the syndrome of `continuous muscle-fibre activity' have been followed-up for 14 years. These patients have gradually gone into remission and no longer require therapy. The results of recent histology, histochemistry, and electronmicroscopy, as well as sural nerve biopsy studies, are presented. The sarcoplasmic reticulum calcium binding activity and ATPase activity are normal. Images PMID:4281819

Peripheral vascular effects of bretylium tosylate in man.

PubMed

Blair, D A; Glover, W E; Kidd, B S; Roddie, I C

1960-09-01

After intra-arterial infusion of bretylium tosylate (12.5 mg.), the reflex changes in vasoconstrictor tone which normally occur in the forearm with body cooling, positive pressure breathing, the Valsalva manoeuvre and postural change were greatly reduced or abolished. Reflex vasodilatation mediated by cholinergic fibres in response to body heating or to emotional stress was little affected. It was concluded that bretylium can selectively block the activity of sympathetic noradrenergic fibres without causing a similar block of sympathetic cholinergic fibres. As the responses to intravenous or intra-arterial infusions of adrenaline or noradrenaline were not reduced after bretylium, it was concluded that bretylium interferes with the activity of noradrenergic fibres rather than with the activity of the noradrenaline released at the nerve ending. After bretylium infusion, forearm and hand blood flow did not often rise to levels characteristic of full release of vasoconstrictor tone. As infusion of bretylium into a nerve-blocked forearm resulted in a pronounced reduction in flow, it is concluded that bretylium also has a constrictor effect on blood vessels. The state of the vessels following an infusion of bretylium appears to depend on the balance between this constrictor action and the longer-acting sympathetic blocking effect.

The distribution and origin of a novel brain peptide, neuropeptide Y, in the spinal cord of several mammals.

PubMed

Gibson, S J; Polak, J M; Allen, J M; Adrian, T E; Kelly, J S; Bloom, S R

1984-07-20

The distribution of neuropeptide Y [NPY]-immunoreactive material was examined in the spinal cord and dorsal root ganglia of rat, guinea-pig, cat, marmoset, and horse. Considerable concentrations of NPY and similar distribution patterns of immunoreactive nerve fibres were found in the spinal cord of all species investigated. The dorsal root ganglia of the cat and the horse contained numerous immunoreactive nerve fibres, but in these species, as in the other three studied [rat, guinea-pig, marmoset], no positively stained cell bodies were found. Neuropeptide Y-immunoreactive nerves were observed at all levels of the spinal cord, being most concentrated in the dorsal horn. In the rat, guinea-pig, and marmoset, there was a marked increase of NPY-immunoreactive fibres in the lumbosacral regions of the spinal cord, and this was reflected by a considerable increase of extractable NPY. Estimations of NPY-immunoreactive material in the various regions of the rat spinal cord were as follows: cervical, 13.8 +/- 1.0; thoracic, 21.1 +/- 2.5; lumbar, 16.3 +/- 2.9; sacral, 92.4 +/- 8.5 pmol/gm wet weight of tissue +/- SEM. In the ventral portion of the guinea-pig spinal cord they were as follows: cervical, 7.1 +/- 1.2; thoracic, 8.2 +/- 3.6; lumbar, 22.6 +/- 7.0; sacral, 36.7 +/- 9.5 pmol/gm wet weight of tissue +/- SEM. Analysis of spinal cord extracts by reverse phase high performance liquid chromatography [HPLC] demonstrated that NPY-immunoreactive material elutes in the position of pure NPY standard. No changes in the concentration and distribution of the NPY-like material in the rat spinal cord were observed following a variety of surgical and pharmacological manipulations, including cervical rhizotomy, sciatic nerve section and ligation, and local application of capsaicin [50 mM] to one sciatic nerve. It is therefore suggested that most of the NPY-immunoreactive material in the spinal cord is derived either from intrinsic nerve cell bodies or from supraspinal tracts.

Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy

PubMed Central

Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F.

2015-01-01

Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies. PMID:26460719

The perception threshold counterpart to dynamic and static mechanical allodynia assessed using von Frey filaments in peripheral neuropathic pain patients.

PubMed

Landerholm, Åsa H; Hansson, Per T

2017-12-29

Background and aim Pain due to a usually non-painful mechanical stimulus, mechanical allodynia, is an oppressive symptom in subgroups of patients with neuropathic pain. Dynamic mechanical allodynia (DMA) is evoked by a normally innocuous light moving mechanical stimulus on the skin and static mechanical allodynia (SMA) by a sustained, normally innocuous pressure against the skin. DMA is claimed to be mediated by myelinated fibres and SMA by C-fibres. Also A-delta fibres have been implicated in the static subtype. A low intensity vertically applied stimulus of 1 second (s) is expected to activate predominantly rapidly adapting A-beta mechanoreceptors thus recruiting the same peripheral substrate as a horizontally moving brush on top of the skin. In patients with SMA we assumed an activation of Cbut also A-delta fibres from a static 10 s von Frey filament stimulus. The aim was to investigate if DMA and SMA could be assessed at perception threshold level using short or longer lasting usually non-painful von Frey filament prodding of the neuropathic skin. Patients and methods Eighteen patients with painful unilateral partial peripheral traumatic nerve injury suffering from SMA (n = 9) and/or DMA (n = 18) in a limb were studied. A compression/ischemia-induced (differential) nerve block in conjunction with repeated quantitative sensory testing of A-delta and C-fibre function using cold and warm stimuli was used to assess which nerve fibre population that contributes to pain at perception threshold level using 1 s (vF1) and 10 s (vF10) von Frey filament stimulation of the skin. Results The main outcome was the finding that elevation of vF1 and vF10 occurred simultaneously and significantly prior to an increase in the perception level to cold or warmth during the continuous nerve block. Single patients demonstrated a slight decrease in cold perception levels at the time of elevation of vF1 or vF10 and a possible contribution to mechanical allodynia from A-delta-fibres can therefore not completely be ruled out although the recorded alterations were minor. None of the patients reported an elevation of the perception level to warmth at the time of elevation of vF1 or vF10 excluding contribution from C-fibres. Further, only patients with clinically established SMA (n = 9) reported continuous pain to a sustained 10 s von Frey filament stimulation (vF10). Patients with only DMA (n = 9) reported pain merely for the initial 1-3 s of the total stimulus duration of 10 s and for a few seconds after the filament was lifted from the skin. Conclusions These findings support the role of A-beta fibres as peripheral mediators of both vF1 and vF10 although different receptor organs may be involved, i.e., rapidly (RA) and slowly (SA-I) adapting mechanoreceptors. Implications Techniques to quantify the different allodynias at perception threshold level deserve further attention as possible adjuncts to suprathreshold stimuli in intervention studies aimed at modifying these stimulus-evoked phenomena.

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

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.

Effect of Transcutaneous Electrical Nerve Stimulation on Sensation Thresholds in Patients with Painful Diabetic Neuropathy: An Observational Study

ERIC Educational Resources Information Center

Moharic, Metka

2010-01-01

Transcutaneous electrical nerve stimulation (TENS) is one of the therapies for painful neuropathy. Its analgesic mechanisms probably involve the gate control theory, the physiological block and the endogenous pain inhibitory system. The aim of the study was to determine whether TENS improves small fibre function diminished because of painful…

Dose-response toxicity studies on tributoxyethyl phosphate orally administered to Sprague-Dawley rats

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

Laham, S.; Szabo, J.; Long, G.

The response of the peripheral nervous system to various dose levels of tributoxyethyl phosphate (TBOP) was investigated in Sprague-Dawley rats. Groups of randomized female and male rats (10 rats/gender/dose level) were administered a single oral dose of TBOP (1.0 to 3.2 g/kg for females;1.0 to 9.0 g/kg for males). Physiological parameters were measured in surviving rats three weeks following TBOP administration. A significant reduction (p<0.05) in caudal nerve conduction velocity (NCV) was observed in both female and male rats. Light and electron microscopic examination of sciatic nerve sections showed degenerative changes in both myelinated and unmyelinated fibers of female (2.0more » g/kg) and male (6.8 g/kg) groups. Advanced degeneration was observed only in the highest dose level of both genders (3.2 g/kg for females; 8.0 and 9.0 g/kg for males). Although similar morphological changes were observed in both genders, females were more susceptible than males to the toxic effects of this compound.« less

Limits to the capacity of transplants of olfactory glia to promote axonal regrowth in the CNS.

PubMed

Gudiño-Cabrera, G; Pastor, A M; de la Cruz, R R; Delgado-García, J M; Nieto-Sampedro, M

2000-02-28

Olfactory bulb ensheathing cell (OBEC) transplants promoted axonal regeneration in the spinal cord dorsal root entry zone and in the corticospinal tract. However, OBECs failed to promote abducens internuclear neuron axon regeneration when transplanted at the site of nerve fibre transection. In experiments performed in both cats and rats, OBECs survived for up to 2 months, lining themselves up along the portion of the regrowing axons proximal to the interneuron cell body. However, OBECs migrated preferentially towards abducens somata, in the direction opposite to the oculomotor nucleus target. OBECs seem to promote nerve fibre regeneration only where preferred direction of glial migration coincides with the direction of axonal growth towards its target.

Changes of the vasculature and innervation in the anterior segment of the RCS rat eye.

PubMed

May, Christian Albrecht

2011-12-01

Investigating the anterior eye segment vasculature and innervation of dystrophic RCS rats, two major unique findings were observed: in the iris, young adult animals with retinal dystrophy showed an increase in substance P nerve fibres and a dilation of arterioles and capillaries. This finding continued during ageing. In the pars plana region, the surface covered by venules decreased continuously with age. In older animals, this decrease was parallelled by a local decrease of sympathetic TH-positive nerve fibres supplying these venules. For both conditions, no comparable data exists so far in the literature. They might point to a unique situation in the anterior eye segment of the dystrophic RCS rat. Copyright © 2011 Elsevier Ltd. All rights reserved.

Optic neuropathies: the tip of the neurodegeneration iceberg

PubMed Central

Carelli, Valerio; La Morgia, Chiara; Ross-Cisneros, Fred N.; Sadun, Alfredo A.

2017-01-01

Abstract The optic nerve and the cells that give origin to its 1.2 million axons, the retinal ganglion cells (RGCs), are particularly vulnerable to neurodegeneration related to mitochondrial dysfunction. Optic neuropathies may range from non-syndromic genetic entities, to rare syndromic multisystem diseases with optic atrophy such as mitochondrial encephalomyopathies, to age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease where optic nerve involvement has, until recently, been a relatively overlooked feature. New tools are available to thoroughly investigate optic nerve function, allowing unparalleled access to this part of the central nervous system. Understanding the molecular pathophysiology of RGC neurodegeneration and optic atrophy, is key to broadly understanding the pathogenesis of neurodegenerative disorders, for monitoring their progression in describing the natural history, and ultimately as outcome measures to evaluate therapies. In this review, the different layers, from molecular to anatomical, that may contribute to RGC neurodegeneration and optic atrophy are tackled in an integrated way, considering all relevant players. These include RGC dendrites, cell bodies and axons, the unmyelinated retinal nerve fiber layer and the myelinated post-laminar axons, as well as olygodendrocytes and astrocytes, looked for unconventional functions. Dysfunctional mitochondrial dynamics, transport, homeostatic control of mitobiogenesis and mitophagic removal, as well as specific propensity to apoptosis may target differently cell types and anatomical settings. Ultimately, we can envisage new investigative approaches and therapeutic options that will speed the early diagnosis of neurodegenerative diseases and their cure. PMID:28977448

BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury.

PubMed

Lopes, Cátia D F; Gonçalves, Nádia P; Gomes, Carla P; Saraiva, Maria J; Pêgo, Ana P

2017-03-01

Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.

The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn.

PubMed

Todd, A J; Hughes, D I; Polgár, E; Nagy, G G; Mackie, M; Ottersen, O P; Maxwell, D J

2003-01-01

Two vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid-lumbar spinal cord of the rat. The great majority (94-100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2-immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin- and enkephalin-containing boutons (including somatostatin-immunoreactive boutons that lacked calcitonin gene-related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present. We also investigated VGLUT expression in central terminals of primary afferents. Myelinated afferents were identified with cholera toxin B subunit; most of those in lamina I were VGLUT2-immunoreactive, whereas all those in deeper laminae were VGLUT1-immunoreactive, and some (in laminae III-VI) appeared to contain both transporters. However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2-immunoreactivity, or were not immunoreactive with either VGLUT antibody. As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter.

A Mathematical Evaluation of the Core Conductor Model

PubMed Central

Clark, John; Plonsey, Robert

1966-01-01

This paper is a mathematical evaluation of the core conductor model where its three dimensionality is taken into account. The problem considered is that of a single, active, unmyelinated nerve fiber situated in an extensive, homogeneous, conducting medium. Expressions for the various core conductor parameters have been derived in a mathematically rigorous manner according to the principles of electromagnetic theory. The purpose of employing mathematical rigor in this study is to bring to light the inherent assumptions of the one dimensional core conductor model, providing a method of evaluating the accuracy of this linear model. Based on the use of synthetic squid axon data, the conclusion of this study is that the linear core conductor model is a good approximation for internal but not external parameters. PMID:5903155

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.

Effects of a sensory branch to the posterior external ear canal: coughing, pain, Ramsay Hunt's syndrome and Hitselberger's sign.

PubMed

Mulazimoglu, S; Flury, R; Kapila, S; Linder, T

2017-04-01

A distinct nerve innervating the external auditory canal can often be identified in close relation to the facial nerve when gradually thinning the posterior canal wall. This nerve has been attributed to coughing during cerumen removal, neuralgic pain, Hitselberger's sign and vesicular eruptions described in Ramsay Hunt's syndrome. This study aimed to demonstrate the origin and clinical impact of this nerve. In patients with intractable otalgia or severe coughing whilst inserting a hearing aid, who responded temporarily to local anaesthesia, the symptoms could be resolved by sectioning a sensory branch to the posterior canal. In a temporal bone specimen, it was revealed that this nerve is predominantly a continuation of Arnold's nerve, also receiving fibres from the glossopharyngeal nerve and facial nerve. Histologically, the communicating branch from the facial nerve was confirmed. Surgeons should be aware of the posterior auricular sensory branch and its clinical implications.

Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.

PubMed

Yasui, M; Shiraishi, Y; Ozaki, N; Hayashi, K; Hori, K; Ichiyanagi, M; Sugiura, Y

2012-08-01

To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing. © 2011 European Federation of International Association for the Study of Pain Chapters.

Electrothermal Equivalent Three-Dimensional Finite-Element Model of a Single Neuron.

PubMed

Cinelli, Ilaria; Destrade, Michel; Duffy, Maeve; McHugh, Peter

2018-06-01

We propose a novel approach for modelling the interdependence of electrical and mechanical phenomena in nervous cells, by using electrothermal equivalences in finite element (FE) analysis so that existing thermomechanical tools can be applied. First, the equivalence between electrical and thermal properties of the nerve materials is established, and results of a pure heat conduction analysis performed in Abaqus CAE Software 6.13-3 are validated with analytical solutions for a range of steady and transient conditions. This validation includes the definition of equivalent active membrane properties that enable prediction of the action potential. Then, as a step toward fully coupled models, electromechanical coupling is implemented through the definition of equivalent piezoelectric properties of the nerve membrane using the thermal expansion coefficient, enabling prediction of the mechanical response of the nerve to the action potential. Results of the coupled electromechanical model are validated with previously published experimental results of deformation for squid giant axon, crab nerve fibre, and garfish olfactory nerve fibre. A simplified coupled electromechanical modelling approach is established through an electrothermal equivalent FE model of a nervous cell for biomedical applications. One of the key findings is the mechanical characterization of the neural activity in a coupled electromechanical domain, which provides insights into the electromechanical behaviour of nervous cells, such as thinning of the membrane. This is a first step toward modelling three-dimensional electromechanical alteration induced by trauma at nerve bundle, tissue, and organ levels.

Glucagon-like peptide 1 receptor (GLP-1R) expression by nerve fibres in inflammatory bowel disease and functional effects in cultured neurons.

PubMed

Anand, Uma; Yiangou, Yiangos; Akbar, Ayesha; Quick, Tom; MacQuillan, Anthony; Fox, Mike; Sinisi, Marco; Korchev, Yuri E; Jones, Ben; Bloom, Steve R; Anand, Praveen

2018-01-01

Glucagon like-peptide 1 receptor (GLP-1R) agonists diminish appetite and may contribute to the weight loss in inflammatory bowel disease (IBD). The aim of this study was to determine, for the first time, the expression of GLP-1R by colon nerve fibres in patients with IBD, and functional effects of its agonists in cultured rat and human sensory neurons. GLP-1R and other nerve markers were studied by immunohistochemistry in colon biopsies from patients with IBD (n = 16) and controls (n = 8), human dorsal root ganglia (DRG) tissue, and in GLP-1R transfected HEK293 cells. The morphological effects of incretin hormones oxyntomodulin, exendin-4 and glucagon were studied on neurite extension in cultured DRG neurons, and their functional effects on capsaicin and ATP signalling, using calcium imaging. Significantly increased numbers of colonic mucosal nerve fibres were observed in IBD biopsies expressing GLP-1R (p = 0.0013), the pan-neuronal marker PGP9.5 (p = 0.0008), and sensory neuropeptide CGRP (p = 0.0014). An increase of GLP-1R positive nerve fibres in IBD colon was confirmed with a different antibody to GLP-1R (p = 0.016). GLP-1R immunostaining was intensely positive in small and medium-sized neurons in human DRG, and in human and rat DRG cultured neurons. Co-localization of GLP-1R expression with neuronal markers in colon and DRG confirmed the neural expression of GLP-1R, and antibody specificity was confirmed in HEK293 cells transfected with the GLP-1R. Treatment with oxyntomodulin, exendin-4 and GLP-1 increased neurite length in cultured neurons compared with controls, but did not stimulate calcium influx directly, or affect capsaicin responses. However, exendin-4 significantly enhanced ATP responses in human DRG neurons. Our results show that increased GLP-1R innervation in IBD bowel could mediate enhanced visceral afferent signalling, and provide a peripheral target for therapeutic intervention. The differential effect of GLP-1R agonists on capsaicin and ATP responses in neurons suggest they may not affect pain mechanisms mediated by the capsaicin receptor TRPV1, but may enhance the effects of purinergic agonists.

Glucagon-like peptide 1 receptor (GLP-1R) expression by nerve fibres in inflammatory bowel disease and functional effects in cultured neurons

PubMed Central

Yiangou, Yiangos; Akbar, Ayesha; Quick, Tom; MacQuillan, Anthony; Fox, Mike; Sinisi, Marco; Korchev, Yuri E.; Jones, Ben; Bloom, Steve R.; Anand, Praveen

2018-01-01

Introduction Glucagon like-peptide 1 receptor (GLP-1R) agonists diminish appetite and may contribute to the weight loss in inflammatory bowel disease (IBD). Objectives The aim of this study was to determine, for the first time, the expression of GLP-1R by colon nerve fibres in patients with IBD, and functional effects of its agonists in cultured rat and human sensory neurons. Methods GLP-1R and other nerve markers were studied by immunohistochemistry in colon biopsies from patients with IBD (n = 16) and controls (n = 8), human dorsal root ganglia (DRG) tissue, and in GLP-1R transfected HEK293 cells. The morphological effects of incretin hormones oxyntomodulin, exendin-4 and glucagon were studied on neurite extension in cultured DRG neurons, and their functional effects on capsaicin and ATP signalling, using calcium imaging. Results Significantly increased numbers of colonic mucosal nerve fibres were observed in IBD biopsies expressing GLP-1R (p = 0.0013), the pan-neuronal marker PGP9.5 (p = 0.0008), and sensory neuropeptide CGRP (p = 0.0014). An increase of GLP-1R positive nerve fibres in IBD colon was confirmed with a different antibody to GLP-1R (p = 0.016). GLP-1R immunostaining was intensely positive in small and medium-sized neurons in human DRG, and in human and rat DRG cultured neurons. Co-localization of GLP-1R expression with neuronal markers in colon and DRG confirmed the neural expression of GLP-1R, and antibody specificity was confirmed in HEK293 cells transfected with the GLP-1R. Treatment with oxyntomodulin, exendin-4 and GLP-1 increased neurite length in cultured neurons compared with controls, but did not stimulate calcium influx directly, or affect capsaicin responses. However, exendin-4 significantly enhanced ATP responses in human DRG neurons. Conclusion Our results show that increased GLP-1R innervation in IBD bowel could mediate enhanced visceral afferent signalling, and provide a peripheral target for therapeutic intervention. The differential effect of GLP-1R agonists on capsaicin and ATP responses in neurons suggest they may not affect pain mechanisms mediated by the capsaicin receptor TRPV1, but may enhance the effects of purinergic agonists. PMID:29813107

Straatsma syndrome: Satisfactory amblyopia treatment. Report of two cases.

PubMed

Quezada-Del Cid, N C; Zimmermann-Paiz, Martin A; Ordoñez-Rivas, A M; Burgos-Elías, V Y; Marroquin-Sarti, M J

2018-06-01

The cases are presented on 2 female patients with Straatsma syndrome, with satisfactory treatment of amblyopia. The level of anisometropia and myelination of retinal nerve fibres were different in these two patients. However, both achieved 0.20 (logMAR) visual acuity with correction in both eyes following amblyopia treatment with ocular patching. Visual prognosis of amblyopia associated with myelination of retinal nerve fibres and anisometropia is poorer than anisometropic amblyopia without myelination. It is well known that the former is refractory to occlusive therapy. Despite having a poor prognosis, visual rehabilitation should be attempted. The two cases presented were successfully treated with eye-patching. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Innervation pattern of the preocular human central retinal artery.

PubMed

Bergua, Antonio; Kapsreiter, Markus; Neuhuber, Winfried L; Reitsamer, Herbert A; Schrödl, Falk

2013-05-01

The central retinal artery (CRA) is the main vessel for inner retinal oxygen and nutrition supply. While the intraocular branches lack autonomic innervation, the innervation pattern of the extra-ocular part of this vessel along its course within the optic nerve is poorly investigated. This part however is essential for maintenance of retinal blood supply, in physiological and pathological conditions. Therefore, the aim of this study was the characterization of the autonomic innervation of the preocular CRA in humans with morphological methods. Meeting the Declaration of Helsinki, eyes of body or cornea donors were processed for single or double immunohistochemistry against tyrosine hydroxilase (TH), dopamine-β-hydroxylase (DBH), choline acetyl-transferase (ChAT), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), and cytochemistry for NADPH-diaphorase (NADPH-d). For documentation, light-, fluorescence-, and confocal laser-scanning microscopy were used. TH and DBH immunoreactive nerve fibres were detected in the CRA vessel wall, although a distinct perivascular plexus was missing. Further, nerve fibres immunoreactive for ChAT and VAChT were found, while CGRP, SP, and VIP were not detected. NADPH-d staining revealed scattered nerve fibres in the adventitia of the CRA and in close vicinity; however, nNOS-immunostaining could not confirm this finding. The CRA receives adrenergic and cholinergic innervations, indicating sympathetic and parasympathetic components, respectively. Remarkably, a peptidergic primary afferent innervation was missing. Since clinical results suggest an autoregulation of intraretinal vessels, further studies are needed to clarify the impact of CRA innervation for retinal perfusion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability

PubMed Central

2010-01-01

Background Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG) to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study. Methods Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle. Results Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6) and 72% of muscles (n = 22) on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8) and 13% of muscles (n = 32) on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14) or muscles (n = 56) tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7) and 32% of muscles (n = 32) on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22) and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6). Conclusions Abnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve hyperexcitability, detectable on EMG on days 2 to 4 post-treatment. Objective EMG assessment of motor nerve excitability could compliment patient-reported symptomatic endpoints of acute oxaliplatin-induced neurotoxicity in future studies. PMID:20731872

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Changes in crossed spinal reflexes after peripheral nerve injury and repair.

PubMed

Valero-Cabré, Antoni; Navarro, Xavier

2002-04-01

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300-400%) and C2 (150-350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

Neuroprotective effects of a new skin care formulation following ultraviolet exposure.

PubMed

Fonseca, B L; dos Santos, B C; Martins, P; Bonorino, C; Corte, T W F; da Silva, V D; Bauer, M E

2012-02-01

Chronic ultraviolet (UV) exposure is a major environmental factor involved in extrinsic skin ageing (photo-ageing). Skin nerve fibres are significantly reduced in number following UV irradiation and new skincare compounds with neuroprotective effects are thus highly warranted. We developed a new skincare formulation from a plant extract and evaluated its neuroprotective effects of ex vivo UV irradiation. The new skincare emulsion was formulated from Echinacea purpurea extract and was enriched with antioxidants (patent no. PROV020110087075). Skin samples were obtained from 20 healthy patients enrolled for plastic surgery and were immediately treated with placebo (SPF 15) or test emulsions. Skin samples were exposed to UVA and UVB for 60 min. Nerve fibres were identified by immunofluorescence using a monoclonal antibody, anti-human CD56. Cell damage was quantified by image analysis. UVA and UVB significantly reduced (40-60%) densities of nerve endings in control samples treated with placebo (P < 0.001). Samples treated with test emulsion completely blocked UV-related effects on skin nerve endings. These neuroprotective effects were similarly observed regardless of age or tissue analysed (breast versus abdomen). Our new skincare formulation obtained from E. purpurea provides important neuroprotective effects of UV irradiation and could be used together with SPFs to prevent chronic deleterious effects of solar exposure. © 2011 Blackwell Publishing Ltd.

Relation between trinucleotide GAA repeat length and sensory neuropathy in Friedreich's ataxia.

PubMed

Santoro, L; De Michele, G; Perretti, A; Crisci, C; Cocozza, S; Cavalcanti, F; Ragno, M; Monticelli, A; Filla, A; Caruso, G

1999-01-01

To verify if GAA expansion size in Friedreich's ataxia could account for the severity of sensory neuropathy. Retrospective study of 56 patients with Friedreich's ataxia selected according to homozygosity for GAA expansion and availability of electrophysiological findings. Orthodromic sensory conduction velocity in the median nerve was available in all patients and that of the tibial nerve in 46 of them. Data of sural nerve biopsy and of a morphometric analysis were available in 12 of the selected patients. The sensory action potential amplitude at the wrist (wSAP) and at the medial malleolus (m mal SAP) and the percentage of myelinated fibres with diameter larger than 7, 9, and 11 microm in the sural nerve were correlated with disease duration and GAA expansion size on the shorter (GAA1) and larger (GAA2) expanded allele in each pair. Pearson's correlation test and stepwise multiple regression were used for statistical analysis. A significant inverse correlation between GAA1 size and wSAP, m mal SAP, and percentage of myelinated fibres was found. Stepwise multiple regression showed that GAA1 size significantly affects electrophysiological and morphometric data, whereas duration of disease has no effect. The data suggest that the severity of the sensory neuropathy is probably genetically determined and that it is not progressive.

Development of a voltage-dependent current noise algorithm for conductance-based stochastic modelling of auditory nerve fibres.

PubMed

Badenhorst, Werner; Hanekom, Tania; Hanekom, Johan J

2016-12-01

This study presents the development of an alternative noise current term and novel voltage-dependent current noise algorithm for conductance-based stochastic auditory nerve fibre (ANF) models. ANFs are known to have significant variance in threshold stimulus which affects temporal characteristics such as latency. This variance is primarily caused by the stochastic behaviour or microscopic fluctuations of the node of Ranvier's voltage-dependent sodium channels of which the intensity is a function of membrane voltage. Though easy to implement and low in computational cost, existing current noise models have two deficiencies: it is independent of membrane voltage, and it is unable to inherently determine the noise intensity required to produce in vivo measured discharge probability functions. The proposed algorithm overcomes these deficiencies while maintaining its low computational cost and ease of implementation compared to other conductance and Markovian-based stochastic models. The algorithm is applied to a Hodgkin-Huxley-based compartmental cat ANF model and validated via comparison of the threshold probability and latency distributions to measured cat ANF data. Simulation results show the algorithm's adherence to in vivo stochastic fibre characteristics such as an exponential relationship between the membrane noise and transmembrane voltage, a negative linear relationship between the log of the relative spread of the discharge probability and the log of the fibre diameter and a decrease in latency with an increase in stimulus intensity.

[Visual function evaluation in human immunodeficiency virus carriers].

PubMed

Solís-Castillo, A; Ramírez-Ponce, L A; Valdez-González, T; Seijo, E; Voorduin-Ramos, S; López-Star, E M

2011-04-01

To determine whether there are changes in the peripapillary nerve fibre layer, in colour vision, contrast sensitivity, dark adaptation and electroretinography changes in these patients who do not have infectious retinitis. We studied 52 patients without ocular pathology; the mean age was 35.88 years old. We observed less thickness in all quadrants, except the nasal. The colour vision was altered in 27.77% of the patients. The contrast sensitivity test showed high frequency alterations. There was no statistically significant difference in the electroretinography test or in dark adaptation. There are changes in the peripapillary nerve fibre layer thickness; also we found changes in colour vision, contrast sensitivity and a decreasing trend of the B wave in the electroreninogram. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Influence of neonatally administered capsaicin on baroreceptor and chemoreceptor reflexes in the adult rat.

PubMed Central

Bond, S. M.; Cervero, F.; McQueen, D. S.

1982-01-01

1 Baroreceptor and chemoreceptor reflex activity was studied in anaesthetized adult rats which had been treated neonatally with a single injection of capsaicin (50 mg/kg s.c.). 2 Pressor responses to bilateral carotid artery occlusion were significantly lower in capsaicin-treated rats compared with vehicle-treated controls. Pressor responses to intravenously injected noradrenaline were similar in the two groups of rats. 3 Resting respiratory minute volume and tidal volume were lower in anaesthetized capsaicin-treated animals than in vehicle-treated controls, but there was no significant difference in respiratory frequency. 4 The increases in respiration evoked by intravenous administration of the peripheral arterial chemoreceptor stimulant, sodium cyanide, or by breathing a hypoxic gas mixture, were significantly lower in capsaicin-treated rats compared with the controls. 5 It is concluded that baroreceptor and chemoreceptor reflex activity are significantly reduced in anaesthetized adult rats which had been treated neonatally with capsaicin, and that this is likely to result from the destruction of unmyelinated baro- and chemoreceptor afferent fibres. PMID:6182938

Distribution of cocaine- and amphetamine-regulated transcript in the hippocampal formation of the guinea pig and domestic pig.

PubMed

Kolenkiewicz, M; Robak, A; Równiak, M; Bogus-Nowakowska, K; Całka, J; Majewski, M

2009-02-01

This study provides a detailed description concerning the distribution of cocaineand amphetamine-regulated transcript (CART) subunits - CART(61-102) and rhCART(28-116) - in the hippocampal formation (HF) of the guinea pig and domestic pig, focussing on the dentate gyrus (DG) and hippocampus proper (HP). Although in both studied species CART-immunoreactive (CART-IR) neuronal somata and processes were present generally in the same layers, some species-specific differences were still found. In the granular layer (GL) of both species, the ovalshaped neurons and some thick varicose fibres were encountered. In the guinea pig there was an immunoreactive "band of dots", probably representing crosssectioned terminals within the DG molecular layer (MOL), whereas in the domestic pig, some varicose fibres were detected, thus suggesting a different orientation of, at least, some nerve terminals. Furthermore, some CART-positive cells and fibres were observed in the hilus (HL) of the guinea pig, whereas in the analogical part of the domestic pig only nerve terminals were labelled. In both species, in the pyramidal layer (PL) of the hippocampus proper, CART-IR triangular somata were observed in the CA3 sector, as well as some positive processes in MOL; however, a few immunoreactive perikarya were found only in the CA1 sector of the guinea pig. As regards the localization patterns of two isoforms of CART in the guinea pig, both peptide fragments were present simultaneously in each of the labelled neurons or fibres, whereas in the domestic pig three types of fibres may be distinguished within the area of the DG. In the hilus and MOL of the dentate gyrus, there were fibres expressing both isoforms of CART in their whole length (fibres of the first type). Fibres of the second type (in GL) coexpressed both peptides only on their short segments, and the last ones (in MOL) expressed solely rhCART(28-116). These results indicate that the distribution of the two CART isoforms are specifically related, thus the relationship between the two CART isoforms may imply different metabolic profiles of CART-expressing neurons.

Central projections and entries of capsaicin-sensitive muscle afferents.

PubMed

Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

1996-03-25

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Acute pandysautonomia: mass spectrometric and histopathological studies of the sympathetic nervous system during long term L-threo-3,4-dihydroxyphenylserine treatment.

PubMed Central

Ushiyama, M; Ikeda, S; Suzuki, T; Yazawa, M; Yanagisawa, N; Tsujino, S

1996-01-01

Stable isotope labelled L-threo-3,4-dihydroxyphenylserine (L-DOPS) infusion tests and histopathological studies of the rectal autonomic nerves were performed in a patient with acute pandysautonomia. A pronounced increase in blood pressure occurred and stable isotope labelled noradrenaline appeared in the plasma during L-DOPS infusion in the acute stage, but decreased during the next three years. Noradrenergic nerve fibres in the rectal mucosa showed no recovery, and so clinical improvement had occurred without apparent significant regeneration of the peripheral autonomic nerves. Images PMID:8676171

Study of long term structural and functional changes in medically controlled glaucoma

PubMed Central

Pandey, Achyut N; Sujata, S

2014-01-01

AIM Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. METHODS Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. RESULTS A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. CONCLUSION Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide. PMID:24634878

Study of long term structural and functional changes in medically controlled glaucoma.

PubMed

Pandey, Achyut N; Sujata, S

2014-01-01

Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide.

Morphology and innervation pattern of the feline urogenital junction.

PubMed

Wrobel, K H; Gürtler, A

2004-12-01

The feline urogenital junction is situated between the extratesticular rete and the spacious initial segments of the efferent ductules. The rete epithelium is cuboidal to low columnar. The rete cells forming the junction rest on a wavy basal lamina, display deep mutual invaginations, possess central nuclei with several infoldings and form a distinct border with the columnar epithelial cells of the initial segments of the ductuli efferentes. The epithelium of the initial segments is composed of ciliated cells and non-ciliated principal cells. The latter are the dominating type and characterized by an apical brush-border and a supranuclear endocytotic apparatus. The stroma of the extratesticular rete contains an abundance of collagen whereas contractile cells are here generally absent. In contrast, the initial segments of the efferent ductules are surrounded by elastic fibres and a layer of contractile cells. All nerves for the feline urogenital junction come from the nervus spermaticus superior. In the epididymal head, small nerve bundles deviate into the septa between the ductules. Single fibres establish a dense network within the muscular coat of the ductuli. At the transition to the extratesticular rete, this network ends abruptly. Nerve fibres in the confines of the rete are associated with blood vessels or proceed to the testicular interior, but establish no relationships with the rete epithelium or the myofibroblasts of the mediastinum. The nervous network in the walls of the efferent ductules and their initial segments is not only composed of sympathetic but also parasympathetic, non-myelinated fibres. Particularly noteworthy is the abundance of calcitonin gene-related peptide (CGRP)- and substance P (SP)-containing axons around the initial segments. Both neuroproteins are consistent markers for sensory neurones. Taken together, it can be assumed that the entry of seminal fluid and spermatozoa into the efferent ductules is controlled by a regulatory nervous chain provided with afferent and efferent components.

Innovative neurophysiological methods in itch research: long-latency evoked potentials after electrical and thermal stimulation in patients with atopic dermatitis.

PubMed

Yudina, Marina M; Toropina, Galina G; Lvov, Andrey; Gieler, Uwe

2011-10-01

The aim of this study was to examine the findings of innovative neurophysiological methods of itch research. Short-latency and pain-related somatosensory-evoked potentials after electrical stimulation, as well as long-latency evoked potentials after thermal stimulation were studied in 38 patients with atopic dermatitis (AD) and 26 healthy volunteers. Quantitative Sensory Testing of thermal perception was performed in 22 patients with AD from the main AD group and in 15 healthy volunteers. Brain hyperactivity to electrical stimuli, delayed thermal-evoked potentials and elevated thermal thresholds were revealed in patients with AD compared with healthy controls. The data indicate small nerve fibre dysfunction in patients with AD, which may contribute to the pathogenesis of AD and chronic itch. The study demonstrates objective approaches to assess the function of small nerve fibres in patients with chronic itch.

The therapeutic potential of renin angiotensin aldosterone system (RAAS) in chronic pain: from preclinical studies to clinical trials.

PubMed

Bessaguet, Flavien; Magy, Laurent; Desmoulière, Alexis; Demiot, Claire

2016-01-01

The prevalence rate of chronic pain is 15% to 25% in adults while the therapeutic arsenal is still insufficient, especially in relieving neuropathic pain. Peripheral pain transmission is conducted by the small Aδ and C sensory nerve fibres. They express elements from the renin-angiotensin-aldosterone system (RAAS), a well-known blood pressure regulator. Recently, studies have demonstrated the role of angiotensin II, its derivatives and aldosterone in the modulation of pain perception, by interacting with receptors expressed by sensory nerve fibres or through the central nervous system. Here, we assess the effects of RAAS modulators in the conduction of pain with molecular, preclinical and clinical approaches, in normal or pathological conditions. Currently, some clinical studies have been carried out on the pain-relieving effect of RAAS modulators and suggest their potential in the management of chronic, inflammatory or neuropathic pain.

Conduction velocity and refractory period of single motor nerve fibres in antecedent poliomyelitis.

PubMed Central

Borg, K; Borg, J

1987-01-01

The axonal conduction velocity and the axonal refractory period were determined using electromyographic techniques for 60 single motor units in 11 patients with antecedent poliomyelitis. The results were compared with previous observations in healthy subjects as well as subjects with motor neuron disease. In antecedent poliomyelitis there was a reduced proportion of nerve fibres with low conduction velocity as compared with the findings in healthy subjects. The mean value of the axonal conduction velocities in antecedent poliomyelitis (42.4 +/- 3.7 m/s, M +/- SD) was significantly higher (p less than 0.01) while in motor neuron disease the corresponding value (35.2 +/- 7.8 m/s) was significantly lower (p less than 0.005) than in healthy subjects (39.8 +/- 4.9 m/s). In antecedent poliomyelitis the conduction velocity and refractory period were related as in healthy subjects while abnormally long refractory periods were observed in motor neuron disease. Images PMID:3585356

Pain sensation during cold stimulation of the teeth: differential reflection of A delta and C fibre activity?

PubMed

Mengel, M K; Stiefenhofer, A E; Jyväsjärvi, E; Kniffki, K D

1993-11-01

Cold stimuli of varying intensities were randomly applied to upper middle incisors of 12 healthy young subjects for a mean duration of 2 min by individually adapted thermodes the temperatures of which ranged from +30 degrees C to -30 degrees C. The subjects were asked to rate the magnitude of their pain sensations during application of the stimuli by means of a linear potentiometer according to a category scale. After each stimulus, they were asked to describe the quality of their pain sensations. Cold stimulation of the teeth evoked pain sensations were reproducible that in subsequent trials and could be graded according to stimulation intensity. Below certain individually different threshold thermode temperatures the onset of a stimulus was followed, after a short latency (1.6 +/- 1 sec), by a sharp and shooting pain sensation which immediately decreased after reaching its maximum value while the stimulus was still present. The mean maxima of the pain intensities were correlated to the thermode temperature. In general, this first pain component was followed by a second one (latency: 29.9 +/- 6.3 sec) with a lower threshold temperature, less of an increase in rate and lower magnitude. This was described as a dull, burning pain which was difficult to localize. The human pain ratings are compared to recordings of intradental nerve fibres in the cat and, under the assumption that the response behaviour of human pulpal nerve fibres is comparable to that of the cat, we hypothesize that the first pain component is evoked by intradental A delta fibres exhibiting their typical phasic response behaviour and firing during the initial steep temperature decrease. After some seconds, intradental temperature reached values sufficient to evoke C-fibre activity associated with the second pain component.

Diabetic Foot Syndrome and Corneal Subbasal Nerve Plexus Changes in Congolese Patients with Type 2 Diabetes

PubMed Central

Schober, Hans-Christof; Stachs, Oliver; Baltrusch, Simone; Bambi, Marie Therese; Kilangalanga, Janvier; Winter, Karsten; Kundt, Guenther; Guthoff, Rudolf F.

2015-01-01

Background To study the severity of diabetic neuropathy, diabetic retinopathy and grades of diabetic foot syndrome for correlations with corneal subbasal nerve plexus (SBP) changes in Congolese patients with type 2 diabetes. Methodology/Principal Findings Twenty-eight type 2 diabetes patients with diabetes-related foot ulceration were recruited in a diabetic care unit in Kinshasa, Democratic Republic of Congo. Corneal SBP was investigated by confocal laser-scanning microscopy to analyse nerve fibre density (NFD) [µm/ µm²], number of branches [n] and number of connectivity points [n]. Foot ulceration was graded using the Wagner ulcer classification. Corneal sensitivity (Cochet-Bonnet), Neuropathy Symptom Score (NSS), Neuropathy Disability Score (NDS), ankle-brachial index (ABI) and ophthalmological status were evaluated. Foot ulceration was ranked as mild (Wagner 0-1: 13 patients/46.4%), moderate (Wagner 2-3: 10 patients/35.7%) and severe (Wagner 4-5: 5 patients/17.9%). The correlation between Wagner Score and NFD (p=0.017, r = - 0,454), NDS and NFD (p=0,039, r = - 0.400) as well as Wagner Score and HbA1c (p=0,007, r = - 0.477) was stated. Significant differences in confocal SBP parameters were observed between Wagner 0-1 and Wagner 4 5 (number of branches (p=0.012), number of connectivity points (p=0.001), nerve fibre density (p=0.033)) and ABI (p=0.030), and between Wagner 2-3 and Wagner 4-5 (number of branches (p=0.003), number of connectivity points (p=0.005) and nerve fibre density (p=0.014)). Differences in NDS (p=0.001) and corneal sensation (p=0.032) were significant between Wagner 0-1 and Wagner 2-3. Patients with diabetic retinopathy had significantly longer diabetes duration (p=0.03) and higher NDS (p=0.01), but showed no differences in SBP morphology or corneal sensation. Conclusions/Significance While confirming the diabetic aetiology of foot ulceration due to medial arterial calcification, this study indicates that the grade of diabetic foot syndrome correlates with corneal SBP changes and corneal sensation in patients in sub-Saharan Africa. PMID:25811186

Towards Ultra-High Resolution Fibre Tract Mapping of the Human Brain – Registration of Polarised Light Images and Reorientation of Fibre Vectors

PubMed Central

Palm, Christoph; Axer, Markus; Gräßel, David; Dammers, Jürgen; Lindemeyer, Johannes; Zilles, Karl; Pietrzyk, Uwe; Amunts, Katrin

2009-01-01

Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography. PMID:20461231

Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block

PubMed Central

Brenneis, C; Kistner, K; Puopolo, M; Jo, S; Roberson, DP; Sisignano, M; Segal, D; Cobos, EJ; Wainger, BJ; Labocha, S; Ferreirós, N; Hehn, C; Tran, J; Geisslinger, G; Reeh, PW; Bean, BP; Woolf, C J

2014-01-01

Background and Purpose: Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314. Experimental Approach: We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed. Key Results: Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314. Conclusions and Implications: Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful. PMID:24117225

Causes of peroneal neuropathy associated with orthopaedic leg lengthening in different canine models.

PubMed

Shchudlo, Natalia A; Varsegova, Tatyana N; Shchudlo, Mikhail M; Stepanov, Mikhail A; Yemanov, Andrey A

2018-05-25

Peroneal neuropathy is one of the complications of orthopaedic leg lengthening. Methods of treatment include slowing of distraction and decompression both of which may lead to additional complications. The purpose of this study was to analyse the changes in histologic peroneal nerve structure during experimental orthopaedic lengthening using various modes of manual or automatic distraction. The obtained data provide the basis for better understanding of peroneal neuropathy pathogenesis and refinement of prophylaxis and preventive treatment protocols. Four experimental models of canine leg lengthening using the Ilizarov fixator were studied: 1 (n = 10)-manual distraction-1 mm/day divided into four increments; 2 (n = 12)-automatic distraction-1 mm/day in 60 increments, 3 (n = 9) and 4 (n = 9)-increased rate of high frequency automatic distraction: 3 mm/day in 120 and 180 increments, respectively. In peroneal nerves semi-thin sections cross-sectional fascicular areas, content of adipocytes in epineurium, endoneurial vascularisation, morphometric parameters of nerve fibres were assessed by computerised analysis at the end of distraction and of consolidation periods and 30 days after fixator removal. In Groups 1-2 massive nerve fibre degeneration along with epineural vessels obliteration was revealed in two cases from 22, whereas in Groups 3-4 there were 10 from 18 (p < 0.01). Injuries of perineurium and endoneurial vessels were noted in Group 3, and long-lasting thinning of nerve fascicles in Group 4. The decrease in epineurial fat tissue was revealed in all groups, more drastic in 3. Modifications and injuries of nerve sheaths and blood vessels depending on distraction rate and frequency contribute to peroneal neuropathy. Its mechanical, circulatory and metabolic causes are discussed.

Alterations of the outer retina in non-arteritic anterior ischaemic optic neuropathy detected using spectral-domain optical coherence tomography.

PubMed

Ackermann, Philipp; Brachert, Maike; Albrecht, Philipp; Ringelstein, Marius; Finis, David; Geerling, Gerd; Aktas, Orhan; Guthoff, Rainer

2017-07-01

A characteristic disease pattern may be reflected by retinal layer thickness changes in non-arteritic anterior ischaemic optic neuropathy measured using spectraldomain optical coherence tomography. Retinal layer segmentation is enabled by advanced software. In this study, retinal layer thicknesses in acute and chronic non-arteritic anterior ischaemic optic neuropathy were compared. A single-centre cross-sectional analysis was used. A total of 27 patients (20 age-matched healthy eyes) were included: 14 with acute (<7 days) and 13 patients with chronic non-arteritic anterior ischaemic optic neuropathy. Macular volume and 12° peripapillary ring optical coherence tomography scans were used. The peripapillary thicknesses of the following layers were determined by manual segmentation: retinal nerve fibres, ganglion cells + inner plexiform layer, inner nuclear layer + outer plexiform layer, outer nuclear layer + inner segments of the photoreceptors and outer segments of the photoreceptors to Bruch's membrane. Macular retinal layer thicknesses were automatically determined in volume cubes centred on the fovea. Peripapillary retinal swelling in acute nonarteritic anterior ischaemic optic neuropathy was attributable to retinal nerve fibre layer, ganglion cell layer/inner plexiform layer and outer nuclear layer/segments of the photoreceptors thickening. In chronic cases, peripapillary retinal nerve fibre layer, macular ganglion cell layer and inner plexiform layer thinning were observed. In acute non-arteritic anterior ischaemic optic neuropathy, the inner and outer peripapillary retinal layers are affected by thickness changes. In chronic cases, atrophy of the ganglion cells and their axons and dendrites is evident by inner retinal layer thinning. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Evaluation of intraepidermal nerve fibres in the skin of normal and atopic dogs.

PubMed

Laprais, Aurore; Dunston, Stanley M; Torres, Sheila M F; Favrot, Claude; Olivry, Thierry

2017-08-01

Interest in intraepidermal nerve fibres (IENFs) is rising in human medicine, because variations in fibre density occur in some diseases and these neurites might contribute to disease pathogenesis. An increase in IENF density is seen in human atopic dermatitis (AD); there are no such data in atopic dogs. To compare the prevalence of IENFs in normal and atopic canine skin. Eight millimetre skin punch biopsies were taken from six sites of 25 healthy dogs without dermatitis and compared to lesional and nonlesional skin samples of dogs with AD (23 and 14 dogs, respectively). Thirty micrometre-thick paraffin-embedded sections were stained by indirect immunofluorescence for neuronal beta-3 tubulin. Only sections with detectable dermal nerves were then screened for the presence of IENFs. IENFs were identified in all 25 normal nasal planum sections, but in only one biopsy collected from each of the normal canine haired skin (NCHS) sites. As there was no significant difference in IENF prevalence between NCHS areas, they were grouped together. The rate of detection of IENFs was significantly higher (one-tailed Fisher's test, P = 0.004) in lesional AD specimens (18 of 23; 78%) than in nonlesional AD (four of 14; 29%) and NCHS specimens (four of 111; 4%, P < 0.0001). The prevalence of IENF detection in nonlesional AD samples was significantly higher than in normal canine skin (P = 0.006). IENFs are detected more commonly in canine AD than in normal haired skin; these results are comparable to those seen for human AD. © 2017 ESVD and ACVD.

Irreversible modification of sodium channel inactivation in toad myelinated nerve fibres by the oxidant chloramine-T.

PubMed Central

Wang, G K

1984-01-01

The effects of externally applied chloramine-T on the excitability of single toad myelinated nerve fibres were studied. Chloramine-T is a mild oxidant which reacts specifically with the cysteine and methionine residues of proteins. Chloramine-T prolongs the action potential of a single myelinated fibre by more than 1000-fold. This effect is concentration- and time-dependent; higher concentrations and longer incubation times increase prolongation. Under voltage-clamp conditions, sodium channel inactivation is markedly inhibited by chloramine-T while sodium channel activation remains normal. Prolonged depolarization of the membrane leads to a maintained sodium current. The maintained sodium currents show activation kinetics, dependence on membrane potential, and reversal potentials which are similar to those of normal, inactivating sodium currents in untreated fibres. Both the maintained and the peak sodium currents are equally inhibited by tetrodotoxin. After partial removal of sodium inactivation by brief exposures to chloramine-T, the voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by about 20 mV, even after correction for the non-inactivating component contributed by the maintained current. The phenomena described here imply that cysteine or methionine residues are critical for the sodium channel inactivation processes. The two different modifications of inactivation, its removal shown by the maintained current, and the shift in the voltage-dependence of the remaining inactivatable channels, reveal that at least two separate residues are modified by chloramine-T. PMID:6321714

DIDMOAD syndrome with megacystis and megaureter.

PubMed Central

Chu, P.; Staff, W. G.; Morris, J. A.; Polak, J. M.

1986-01-01

A case of DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and nerve deafness) is described. There was unusually severe urinary tract dilatation which led to an ileal conduit diversion. Immunohistological study of the bladder wall and ureter revealed a marked diminution in nerve fibres, which may have been primary or secondary to the muscle hypertrophy. The possible pathogenesis of the urinary tract dilatation is discussed in relation to this finding. Images Figure 1 Figure 2 Figure 3 PMID:3809079

Risk factors for progressive axonal degeneration of the retinal nerve fibre layer in multiple sclerosis patients.

PubMed

Garcia-Martin, Elena; Pueyo, Victoria; Almarcegui, Carmen; Martin, Jesus; Ara, Jose R; Sancho, Eva; Pablo, Luis E; Dolz, Isabel; Fernandez, Javier

2011-11-01

To quantify structural and functional degeneration in the retinal nerve fibre layer (RNFL) of patients with multiple sclerosis (MS) over a 2-year time period, and to analyse the effect of prior optic neuritis (ON) as well as the duration and incidence of MS relapses. 166 MS patients and 120 healthy controls underwent assessment of visual acuity and colour vision, visual field examination, optical coherence tomography, scanning laser polarimetry and visual evoked potentials (VEPs). All subjects were re-evaluated after a period of 12 and 24 months. Changes in the optic nerve were detected by structural measurements but not by functional assessments. Changes registered in MS patients were greater than changes in healthy controls (p<0.05). Eyes with previous ON showed a greater reduction of parameters in the baseline evaluation, but RNFL atrophy was not significantly greater in the longitudinal study. Patients with MS relapses showed a greater reduction of RNFL thickness and VEP amplitude compared with non-relapsing cases. Patients with and without treatment showed similar measurement reduction, but the non-treated group had a significantly higher increase in Expanded Disability Status Scale (p=0.029). MS causes progressive axonal loss in the optic nerve, regardless of a history of ON. This ganglion cell atrophy occurs in all eyes but is more marked in MS eyes than in healthy eyes.

Expression of the diabetes risk gene wolframin (WFS1) in the human retina

PubMed Central

Schmidt-Kastner, Rainald; Kreczmanski, Pawel; Preising, Markus; Diederen, Roselie; Schmitz, Christoph; Reis, Danielle; Blanks, Janet; Dorey, C. Kathleen

2009-01-01

Wolfram syndrome 1 (WFS1, OMIM 222300), a rare genetic disorder characterized by optic nerve atrophy, deafness, diabetes insipidus and diabetes mellitus, is caused by mutations of WFS1, encoding WFS1/wolframin. Non-syndromic WFS1 variants are associated with the risk of diabetes mellitus due to altered function of wolframin in pancreatic islet cells, expanding the importance of wolframin. This study extends a previous report for the monkey retina, using immunohistochemistry to localize wolframin on cryostat and paraffin sections of human retina. In addition, the human retinal pigment epithelial (RPE) cell line termed ARPE-19 and retinas from both pigmented and albino mice were studied to assess wolframin localization. In the human retina, wolframin was expressed in retinal ganglion cells, optic axons and the proximal optic nerve. Wolframin expression in the human retinal pigment epithelium (RPE) was confirmed with intense cytoplasmic labeling in ARPE-19 cells. Strong labeling of the RPE was also found in the albino mouse retina. Cryostat sections of the mouse retina showed a more extended pattern of wolframin labeling, including the inner nuclear layer (INL) and photoreceptor inner segments, confirming the recent report of Kawano et al. (J. Comp. Neurol. 2008: 510, 1-23). Absence of these cells in the human specimens despite the use of human-specific antibodies to wolframin may be related to delayed fixation. Loss of wolframin function in RGCs and the unmyelinated portion of retinal axons could explain optic nerve atrophy in Wolfram Syndrome 1. PMID:19523951

Pirt contributes to uterine contraction-induced pain in mice.

PubMed

Wang, Changming; Wang, Zhongli; Yang, Yan; Zhu, Chan; Wu, Guanyi; Yu, Guang; Jian, Tunyu; Yang, Niuniu; Shi, Hao; Tang, Min; He, Qian; Lan, Lei; Liu, Qin; Guan, Yun; Dong, Xinzhong; Duan, Jinao; Tang, Zongxiang

2015-09-17

Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin into female mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt (+/+) and Pirt (-/-) mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt (-/-) mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt (+/+) and Pirt (-/-) mice. We found that the writhing responses were less intensive in Pirt (-/-) mice than in Pirt (+/+) mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrograde-labeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin-responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt (-/-) mice. Taken together, we speculate that Pirt plays an important role in mice uterine contraction-induced pain.

Optic nerve lesion following neuroborreliosis: a case report.

PubMed

Burkhard, C; Gleichmann, M; Wilhelm, H

2001-01-01

Neuroborreliosis may cause various neuro-ophthalmological complications. We describe a case with a bilateral optic neuropathy. A 58-year-old female developed facial paresis six weeks after an insect bite. One week later she developed bilateral optic disc swelling with haemorrhages and nerve fibre bundle defects in the lower visual field of the left eye. In CSF and serum, raised IgM and IgG titres to Borrelia burgdorferi were found. Systemic antibiotic treatment led to improvement of the vision and facial paresis, but not all visual field defects resolved, probably due to ischemic lesions of the optic disc. In optic nerve lesions due to neuroborreliosis it is difficult to distinguish between inflammatory and ischemic lesions. This patient demonstrated features of an ischemic optic nerve lesion.

Chronic non-freezing cold injury results in neuropathic pain due to a sensory neuropathy

PubMed Central

Vale, Tom A; Symmonds, Mkael; Polydefkis, Michael; Byrnes, Kelly; Rice, Andrew S C; Themistocleous, Andreas C; Bennett, David L H

2017-01-01

Abstract Non-freezing cold injury develops after sustained exposure to cold temperatures, resulting in tissue cooling but not freezing. This can result in persistent sensory disturbance of the hands and feet including numbness, paraesthesia and chronic pain. Both vascular and neurological aetiologies of this pain have been suggested but remain unproven. We prospectively approached patients referred for clinical assessment of chronic pain following non-freezing cold injury between 12 February 2014 and 30 November 2016. Of 47 patients approached, 42 consented to undergo detailed neurological evaluations including: questionnaires to detail pain location and characteristics, structured neurological examination, quantitative sensory testing, nerve conduction studies and skin biopsy for intraepidermal nerve fibre assessment. Of the 42 study participants, all had experienced non-freezing cold injury while serving in the UK armed services and the majority were of African descent (76.2%) and male (95.2%). Many participants reported multiple exposures to cold. The median time between initial injury and referral was 3.72 years. Pain was principally localized to the hands and the feet, neuropathic in nature and in all study participants associated with cold hypersensitivity. Clinical examination and quantitative sensory testing were consistent with a sensory neuropathy. In all cases, large fibre nerve conduction studies were normal. The intraepidermal nerve fibre density was markedly reduced with 90.5% of participants having a count at or below the 0.05 centile of published normative controls. Using the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain grading for neuropathic pain, 100% had probable and 95.2% definite neuropathic pain. Chronic non-freezing cold injury is a disabling neuropathic pain disorder due to a sensory neuropathy. Why some individuals develop an acute painful sensory neuropathy on sustained cold exposure is not yet known, but individuals of African descent appear vulnerable. Screening tools, such as the DN4 questionnaire, and treatment algorithms for neuropathic pain should now be used in the management of these patients. PMID:28969380

Photogrammetric 3d Acquisition and Analysis of Medicamentous Induced Pilomotor Reflex ("goose Bumps")

NASA Astrophysics Data System (ADS)

Schneider, D.; Hecht, A.

2016-06-01

In a current study at the University Hospital Dresden, Department of Neurology, the autonomous function of nerve fibres of the human skin is investigated. For this purpose, a specific medicament is applied on a small area of the skin of a test person which results in a local reaction (goose bumps). Based on the extent of the area, where the stimulation of the nerve fibres is visible, it can be concluded how the nerve function of the skin works. The aim of the investigation described in the paper is to generate 3D data of these goose bumps. Therefore, the paper analyses and compares different photogrammetric surface measurement techniques in regard to their suitability for the 3D acquisition of silicone imprints of the human skin. Furthermore, an appropriate processing procedure for analysing the recorded point cloud data is developed and presented. It was experimentally proven that by using (low-cost) photogrammetric techniques medicamentous induced goose bumps can be acquired in three dimensions and can be analysed almost fully automatically from the perspective of medical research questions. The relative accuracy was determined with 1% (RMSE) of the area resp. the volume of an individual goose bump.

Response of the gut neuroendocrine system of Leuciscus cephalus (L.) to the presence of Pomphorhynchus laevis Müller, 1776 (Acanthocephala).

PubMed

Bosi, G; Domeneghini, C; Arrighi, S; Giari, L; Simoni, E; Dezfuli, B S

2005-04-01

Immunohistochemical tests were applied to sections of intestine of uninfected and Pomphorhynchus laevis Muller-infected chub, Leuciscus cephalus (L.) using 15 different antisera. Nerve cell bodies and fibres immunoreactive (IR) to the anti-bombesin, -Cholecystokinin-8 (CCK-8), -galanin, -Gastrin-Releasing Peptide (-GRP), -Nitric Oxide Synthase (-NOS), -Substance P (-SP), and -Vasoactive Intestinal Peptide (-VIP) sera were observed in the myenteric plexus of uninfected chub. The density of nerve components immunoreactive to these antisera was high in the intestine of the infected fish, especially near the site of attachment. Moreover, numerous nerve fibres, immunoreactive to anti-bombesin, -GRP, -galanin, -SP, and -VIP sera, were encountered in the connective tissue capsule surrounding the bulb and proboscis of P. laevis. The occurrence of P. laevis in the chub gut significantly increased the number of endocrine cells per intestinal fold immunoreactive to galanin, met-enkephalin and leu-enkephalin antisera. CCK-8, Neuropeptide Y and glucagon-like immunoreactive cells were less numerous in the intestine of infected chub. A large number of cells in the tunica propria-submucosa of L. cephalus infected with P. laevis were immunoreactive to anti-serotonin and -leu-enkephalin sera.

Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs

PubMed Central

Canning, Brendan J; Mazzone, Stuart B; Meeker, Sonya N; Mori, Nanako; Reynolds, Sandra M; Undem, Bradley J

2004-01-01

We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea-pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin-sensitive afferent neurones (both Aδ- and C-fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin-insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Aδ-fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well-defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex. PMID:15004208

Neuropeptide Y in the human male genital tract.

PubMed

Adrian, T E; Gu, J; Allen, J M; Tatemoto, K; Polak, J M; Bloom, S R

1984-12-24

Neuropeptide Y (NPY) was found in high concentrations in the male genital tract. NPY levels were highest in the seminal vesicles, prostate, corpus cavernosum and vas deferens, where large numbers of immunoreactive nerve fibres were detected. Considerable quantities were also found in the epididymis and spongiosum. Lower concentrations were found in the glans penis, testis and foreskin. The presence of a large number of nerves containing NPY suggest that this active neuropeptide may play a role in control of genital function.

Unmyelinated tactile cutaneous nerves signal erotic sensations.

PubMed

Jönsson, Emma H; Backlund Wasling, Helena; Wagnbeck, Vicktoria; Dimitriadis, Menelaos; Georgiadis, Janniko R; Olausson, Håkan; Croy, Ilona

2015-06-01

Intrapersonal touch is a powerful tool for communicating emotions and can among many things evoke feelings of eroticism and sexual arousal. The peripheral neural mechanisms of erotic touch signaling have been less studied. C tactile afferents (unmyelinated low-threshold mechanoreceptors), known to underpin pleasant aspects of touch processing, have been posited to play an important role. In two studies, we investigated the relationship between C tactile activation and the perception of erotic and pleasant touch, using tactile brushing stimulation. In total, 66 healthy subjects (37 women, age range 19-51 years) were examined. In study 1 (n = 20), five different stroking velocities were applied to the forearm and the inner thigh. The participants answered questions about partnership, mood, and touch. In study 2 (n = 46), the same five stroking velocities were applied to the forearm. The participants answered questions about partnership, touch, and sexuality. Both touch eroticism and pleasantness were rated significantly higher for C tactile optimal velocities compared with suboptimal velocities. No difference was found between the ratings of the thigh and the forearm. The velocity-dependent rating curves of pleasantness, intensity, and eroticism differed from each other. Pleasantness was best explained by a quadratic fit, intensity by a linear fit, and eroticism by both. A linear transformation of pleasantness and intensity predicted the observed eroticism ratings reliably. Eroticism ratings were negatively correlated with length of relationship. Touch was rated most erotic when perceived as pleasant and weak. In human hairy skin, perception of pleasantness is correlated with the firing rate of C tactile afferents, and perception of intensity is correlated with the firing rate of Aβ afferents. Accordingly, eroticism may be perceived most readily for touch stimuli that induce high activity in C tactile fibers and low activity in Aβ fibers. © 2015 International Society for Sexual Medicine.

Use of a Novel High-Resolution Magnetic Resonance Neurography Protocol to Detect Abnormal Dorsal Root Ganglia in Sjögren Patients With Neuropathic Pain

PubMed Central

Birnbaum, Julius; Duncan, Trisha; Owoyemi, Kristie; Wang, Kenneth C.; Carrino, John; Chhabra, Avneesh

2014-01-01

Abstract The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional “stocking-and-glove” distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system—the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain. We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients whose neuropathic pain resolved with intravenous immunoglobulin (IVIg) therapy had improvement of MRN DRG abnormalities. We have developed a novel MRN protocol that can detect DRG abnormalities in SS patients with neuropathic pain who do not have markers of peripheral neuropathy. We found that SS patients with MRN DRG abnormalities had statistically significant, increased IENFD on skin biopsy studies, which may suggest a relationship between trophic mediators and neuropathic pain. Given that our literature review has demonstrated that many SS neuropathic pain patients do not have a neuropathy, our findings suggest an important niche for this MRN DRG technique in the evaluation of broader subsets of SS neuropathic pain patients who may not have underlying neuropathies. The improvement of MRN DRG abnormalities in patients with IVIg-induced remission of neuropathic pain suggests that our MRN protocol may be capturing reversible, immune-mediated mechanisms targeting the DRG. PMID:24797167

Retinal Nerve Fiber Layer Thickness in Children With ADHD.

PubMed

Hergüner, Arzu; Alpfidan, İsmail; Yar, Ahmet; Erdoğan, Erkan; Metin, Özge; Sakarya, Yaşar; Hergüner, Sabri

2018-05-01

The current study aims to compare retinal nerve fiber layer (RNFL) thickness, macular thickness, and macular volume between children with ADHD and a control group. The study group included children with ADHD and the control group consisted of age- and gender-matched participants without any psychiatric disorder. In all participants, RNFL thickness, macular thickness, and macular volume were measured by using spectral domain-optical coherence tomography (SD-OCT). ADHD symptom severity was evaluated by using parent-report measures, including Conners' Parent Rating Scale-Revised: Short Form (CPRS-R: S) and the Strengths and Difficulties Questionnaire: Parent Form (SDQ: P). We compared 90 eyes of 45 children with ADHD and 90 eyes of 45 controls. ADHD group had significantly lower RNFL thickness only in nasal quadrant than the controls. The remaining RNFL quadrants, macular thickness, and volume were not significantly different between groups. There was a reverse correlation between RNFL thickness and ADHD symptom severity. This is the first study examining the RNFL thickness in ADHD. Our findings showed that nasal RNFL thickness was lower, indicating reduced unmyelinated axons in the retina of children with ADHD. The results of this study support the evidence that ADHD involves a lag in cortical maturation and this is measurable in the retina.

Region-specific ischemia, neovascularization and macular oedema in treatment-naïve proliferative diabetic retinopathy.

PubMed

Lange, Jason; Hadziahmetovic, Majda; Zhang, Jingfa; Li, Weiye

2018-02-07

Region-specific pathology in proliferative diabetic retinopathy enhances our understanding and management of this disease. To investigate non-perfusion, neovascularization and macular oedema. A cross-sectional, observational, non-randomized study. Consecutive 43 eyes of 27 treatment-naïve patients. Ultra-widefield fluorescein angiography for studying specific zones, that is, far-peripheral zone, mid-peripheral zone and central retina (cr), and spectral-domain optical coherence tomography for analysing thickness of macular layers. Non-perfusion index (NPI) and neovascularization index (NVI) in different zones, thickness of cr, retinal nerve fibre layer, ganglion cell layer (GCL), inner nuclear layer (INL) and outer plexiform layer in parafoveal regions. The NPI of far-periphery and NVI of mid-periphery were the highest by one-way analysis of variance testing. Ischemic retina defined as high NPI in far-periphery was significantly related to macular oedema via a binary classification approach (P < 0.05). The ischemic retina was correlated with a decreased thickness of both retinal nerve fibre and GCL (P < 0.05); macular oedema was correlated with increased INL thickness (P < 0.0001). The region-specific correlation of NPI of far-periphery and NVI of mid-periphery, but not with central retinal thickness, suggests different pathogeneses of neovascularization and macular oedema. Retinal nerve fibre layer and GCL, both biomarkers of diabetic retinal neuronopathy, are associated with retinal ischemia, but not with macular oedema, suggesting that diabetic microangiopathy and neuronopathy possess distinct pathogenic pathways. The strong correlation between macular oedema and INL indicates that intracellular oedema is a determining factor of diabetic macular oedema. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

PubMed

Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B

2017-10-01

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment.

PubMed

Mahelkova, Gabriela; Jirsova, Katerina; Seidler Stangova, Petra; Palos, Michalis; Vesela, Viera; Fales, Ivan; Jiraskova, Nada; Dotrelova, Dagmar

2017-05-01

In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. © 2016 Optometry Australia.

Ganglion cell-inner plexiform layer and retinal nerve fibre layer changes within the macula in retinitis pigmentosa: a spectral domain optical coherence tomography study.

PubMed

Yoon, Chang Ki; Yu, Hyeong Gon

2018-03-01

To investigate how macular ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thicknesses within the macula change with retinitis pigmentosa (RP) severity. Spectral domain optical coherence tomography (SD-OCT) was used to examine 177 patients with RP and 177 normal controls. An optical coherence tomography (OCT) line scan was used to grade RP severity. Retinitis pigmentosa (RP) was categorized as more advanced if there was no identifiable inner segment ellipsoid (ISe) band (NISE) and as less advanced if an ISe band could be identified and peripheral loss of ISe was apparent (IISE). Ganglion cell-inner plexiform layer (GCIPL) and RNFL thicknesses were manually measured on OCT images and analysed. Pearson's correlation analyses were used to examine correlations between GCIPL thickness, RNFL thickness, visual acuity (VA) and visual field extent in patients and controls. Ganglion cell-inner plexiform layer (GCIPL) was significantly thicker in IISE than in control eyes (p < 0.001), but significantly thinner in NISE than in IISE eyes (p < 0.001) in both horizontal and vertical OCT scans. Retinal nerve fibre layer (RNFL) was significantly thicker in eyes with IISE and NISE than in control eyes in both horizontal and vertical meridians (all p < 0.001). Ganglion cell-inner plexiform layer (GCIPL) thickness showed a weak positive correlation with vision, and RNFL thickness showed a weak negative correlation with vision and visual field extent. Based on these results, the inner retina, including the GCIPL and RNFL, maintains its gross integrity longer than the photoreceptor layer in RP. Additionally, thickening of the inner retina may have some functional implications in patients with RP. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges.

PubMed

De Col, Roberto; Messlinger, Karl; Carr, Richard W

2008-02-15

Axonal conduction velocity varies according to the level of preceding impulse activity. In unmyelinated axons this typically results in a slowing of conduction velocity and a parallel increase in threshold. It is currently held that Na(+)-K(+)-ATPase-dependent axonal hyperpolarization is responsible for this slowing but this has long been equivocal. We therefore examined conduction velocity changes during repetitive activation of single unmyelinated axons innervating the rat cranial meninges. In direct contradiction to the currently accepted postulate, Na(+)-K(+)-ATPase blockade actually enhanced activity-induced conduction velocity slowing, while the degree of velocity slowing was curtailed in the presence of lidocaine (10-300 microm) and carbamazepine (30-500 microm) but not tetrodotoxin (TTX, 10-80 nm). This suggests that a change in the number of available sodium channels is the most prominent factor responsible for activity-induced changes in conduction velocity in unmyelinated axons. At moderate stimulus frequencies, axonal conduction velocity is determined by an interaction between residual sodium channel inactivation following each impulse and the retrieval of channels from inactivation by a concomitant Na(+)-K(+)-ATPase-mediated hyperpolarization. Since the process is primarily dependent upon sodium channel availability, tracking conduction velocity provides a means of accessing relative changes in the excitability of nociceptive neurons.

Diabetic peripheral neuropathy assessment through texture based analysis of corneal nerve images

NASA Astrophysics Data System (ADS)

Silva, Susana F.; Gouveia, Sofia; Gomes, Leonor; Negrão, Luís; João Quadrado, Maria; Domingues, José Paulo; Morgado, António Miguel

2015-05-01

Diabetic peripheral neuropathy (DPN) is one common complication of diabetes. Early diagnosis of DPN often fails due to the non-availability of a simple, reliable, non-invasive method. Several published studies show that corneal confocal microscopy (CCM) can identify small nerve fibre damage and quantify the severity of DPN, using nerve morphometric parameters. Here, we used image texture features, extracted from corneal sub-basal nerve plexus images, obtained in vivo by CCM, to identify DPN patients, using classification techniques. A SVM classifier using image texture features was used to identify (DPN vs. No DPN) DPN patients. The accuracies were 80.6%, when excluding diabetic patients without neuropathy, and 73.5%, when including diabetic patients without diabetic neuropathy jointly with healthy controls. The results suggest that texture analysis might be used as a complementing technique for DPN diagnosis, without requiring nerve segmentation in CCM images. The results also suggest that this technique has enough sensitivity to detect early disorders in the corneal nerves of diabetic patients.

The afferent pathways of discogenic low-back pain. Evaluation of L2 spinal nerve infiltration.

PubMed

Nakamura, S I; Takahashi, K; Takahashi, Y; Yamagata, M; Moriya, H

1996-07-01

The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value.

An immunohistochemical screening of neurochemical markers in fungiform papillae and taste buds of the anterior rat tongue.

PubMed

Astbäck, J; Arvidson, K; Johansson, O

1997-02-01

The occurrence and distribution of several neurochemical markers were investigated. Numerous nerve fibres were shown, using antibodies to protein gene product (PGP) 9.5, neurone-specific enolase, calcitonin gene-related peptide (CGRP), substance P. neurokinin A or protein S-100. The presence of vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI), neuropeptide tyrosine, dopamine-beta-hydroxylase (DBH), cholecystokinin/gastrin, glutamate and galanin was more scarce. Nerve fibres containing these above-mentioned markers were found at several locations, i.e. in the epithelium, connective tissue, and around blood vessels. In the taste buds, numerous PGP 9.5, neurone-specific enolase-, CGRP-, substance P-, neurokinin A- and protein S-100-containing structures were found, but few VIP and galanin ones. No immunoreactivity was found with antibodies against somatostatin, bombesin, enkephalin or dynorphin. These findings extend knowledge about the general as well as the neurochemical messenger-based innervation of rat fungiform papillae, forming a firm basis for future functional investigations of normal, experimental and also clinical materials.

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node

PubMed Central

Appel, W. C.; Vincenzi, F. F.

1970-01-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres. 2. In the presence of 2 × 10-4 g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered. 3. In the presence of 5 × 10-6 g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected. 4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium. 5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission. PMID:5492897

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node.

PubMed

Appel, W C; Vincenzi, F F

1970-10-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres.2. In the presence of 2 x 10(-4) g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered.3. In the presence of 5 x 10(-6) g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected.4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium.5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission.

Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs.

PubMed

Cui, Yi; Yao, Yao; Zhao, Yannan; Xiao, Zhifeng; Cao, Zongfu; Han, Sufang; Li, Xing; Huan, Yong; Pan, Juli; Dai, Jianwu

2018-05-01

Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5-cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC-MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC-MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC-MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC-MSCs might have therapeutic potential for the treatment of peripheral nerve injury. Copyright © 2018 John Wiley & Sons, Ltd.

Peripapillary schisis in open-angle glaucoma.

PubMed

Dhingra, N; Manoharan, R; Gill, S; Nagar, M

2017-03-01

PurposeTo report clinical features, topographic findings and outcome of 10 eyes with peripapillary schisis in open-angle glaucoma.Patients and methodsA retrospective review of patients with open-angle glaucoma who were noted to have peripapillary schisis on optical coherence tomography (OCT) were included. Serial peripapillary and macula infrared and OCT images, visual acuity, visual fields, and schisis appearance were reviewed.ResultsTen eyes of nine patients with open-angle glaucoma were detected to have the presence of peripapillary schisis. Nerve fibre layer schisis was detected in all eyes and one eye had an associated macular schisis. None of the eyes had an acquired pit of the optic nerve or pathological myopia. The mean intraocular pressures at detection was 18.3±4.3 mm Hg and the schisis resolved in four eyes after a mean follow-up of 21.2±8.8 months. Visual field worsening was noted in 4 of the 10 eyes and the resolution of schisis resulted in significant reduction in the retinal nerve fibre layer (RNFL) thickness.ConclusionsPeripapillary schisis detected during the normal course of open-angle glaucoma can resolve spontaneously and rarely involves the macula. Its resolution leads to reduction in RNFL thickness; therefore, caution is advised while interpreting serial scans.

Tachykinin antagonists have potent local anaesthetic actions.

PubMed

Post, C; Butterworth, J F; Strichartz, G R; Karlsson, J A; Persson, C G

1985-11-19

Contrary to what would have been expected, an antagonist of substance P (SP) [Arg5,D-Trp7,9]SP-(5-11) inhibited the neurogenic contraction of isolated guinea-pig hilus bronchi more readily than a contraction produced by exogenous SP. Furthermore, it has previously been shown that a tachykinin antagonist given intrathecally produced motor blockade as do local anaesthetic drugs. We therefore examined whether tachykinin antagonists had a depressant action on axonal neurotransmission. The compound action potential (APc) of the frog isolated sciatic nerve was suppressed in a concentration-dependent manner by the tachykinin antagonists [D-Pro2,D-Trp7,9]SP and [Arg5,D-Trp7,9]Sp-(5-11), both being about 4 times more potent than lidocaine. SP itself was without effect. Similarly in the rat isolated sciatic nerve [D-Pro2,D-Trp7,9]SP suppressed the APc. It was more potent in the A alpha- than in the C-fibres. SP did not affect conduction in either fibre type. In conscious guinea-pigs [D-Pro2,D-Trp7,9]SP injected adjacent to the sciatic nerve was found to block motor but not sensory functions of the limb. Thus, commonly used tachykinin antagonists, but not SP itself, have potent local anaesthetic properties. This should be considered when these agents are employed as pharmacological tools.

Gross and microscopic observations on the lingual structure of the Florida Manatee Trichechus manatus latirostris.

PubMed

Levin, M J; Pfeiffer, C J

2002-10-01

The tongue of the Florida manatee (Trichechus manatus latirostris) was studied macroscopically, light and electron microscopically. The tongue was slender, muscular and firmly fixed in the oral cavity; only the cranial tip was free and mobile. Numerous filiform papillae were distributed over the dorsal surface of the rostral tongue. Multiple raised, round fungiform-like papillae were distributed over most of the dorsum. Typical fungiform papillae were restricted to the lateral margins of the tongue. Foliate papillae, presenting as multi-fossulate openings, were noted on the caudolateral margins. Open pits were located on the dorsocaudal surface and lateral walls. Microscopic examination showed that most of the lingual dorsum was covered with a thick stratified squamous epithelium. Open pits led to well-developed mucous salivary glands. Glands within the foliate papillae were mostly mucous, although some seromucous glands were present. Taste buds were restricted to the epithelium of the foliate papillae. Throughout the tongue, striated muscle was abundant below the epithelium. Blood vessels, lymph channels and nerve fibres were freely distributed throughout the intermuscular stroma. Nerve fibres reacted positively with neurone specific enolase (NSE) antibody throughout the tongue, including nerve bundles, glands and taste buds. Clear to translucent vacuoles were found juxtaposed to nuclei in the stratum spinosum in the foliate papillae epithelium.

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons near the implanted electrode shanks, along with dense cellular accumulations near the implant site. Scanning electron microscopy (SEM) showed alterations of the electrode insulation and deformation of electrode shanks. Significance. We describe a comprehensive testing platform with applicability to electrodes that record from the peripheral nerves. This study assesses the long term safety and performance of electrodes in the peripheral nerves using a rodent model. Under this animal test platform, FMA electrodes record single unit action potentials but have limited chronic reliability due to structural weaknesses. Future work will apply these methods to other commercially-available and novel peripheral electrode technologies. This research was carried out in the Division of Biomedical Physics, Office of Science and Engineering Laboratory, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.

Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.

PubMed

Braak, H; Rüb, U; Gai, W P; Del Tredici, K

2003-05-01

The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.

Evaluation of the lamina cribrosa in patients with diabetes mellitus using enhanced depth imaging spectral-domain optical coherence tomography.

PubMed

Akkaya, Serkan; Küçük, Bekir; Doğan, Hatice Karaköse; Can, Ertuğrul

2018-06-01

To compare the lamina cribrosa thickness and anterior lamina cribrosa depth between patients with and without diabetes mellitus and to investigate the effect of metabolic control and duration of diabetes mellitus on lamina cribrosa thickness and anterior lamina cribrosa depth using enhanced depth imaging spectral-domain optical coherence tomography. A total of 70 patients were enrolled in this cross-sectional study and were divided into the diabetes and control groups. Intraocular pressure, circumpapillary retinal nerve fibre layer thickness, anterior lamina cribrosa depth and lamina cribrosa thickness were compared between the groups. In the control group, the mean intraocular pressure was 14.6 ± 3.1 (mean ± standard deviation) mmHg, mean circumpapillary retinal nerve fibre layer thickness was 105.41 ± 5.86 μm, mean anterior lamina cribrosa depth was 420.3 ± 90.2 μm and mean lamina cribrosa thickness was 248.5 ± 5.4 μm. In the diabetes group, the mean intraocular pressure was 13.9 ± 2.2 mmHg, mean circumpapillary retinal nerve fibre layer thickness was 101.37 ± 10.97 μm, mean anterior lamina cribrosa depth was 351.4 ± 58.6 μm and mean lamina cribrosa thickness was 271.6 ± 33.9 μm. Lamina cribrosa thickness was significantly higher ( p < 0.001) and anterior lamina cribrosa depth was significantly lower ( p = 0.003) in the diabetes group. There was no statistical difference between the groups with regard to age, spherical equivalent, axial length, circumpapillary retinal nerve fibre layer thickness and intraocular pressure ( p  = 0.69, 0.26, 0.47, 0.06 and 0.46, respectively). Lamina cribrosa thickness and anterior lamina cribrosa depth were not significantly correlated with duration of diabetes mellitus (lamina cribrosa thickness: r = -0.078, p = 0.643; anterior lamina cribrosa depth: r = -0.062, p = 0.710) or HbA1c levels (lamina cribrosa thickness: r = -0.078, p = 0.596; anterior lamina cribrosa depth: r = -0.228, p = 0.169). The results of this study showed that the optical coherence tomography measurement of lamina cribrosa revealed thicker and more anteriorly positioned lamina cribrosa for patients with diabetes mellitus compared with those for healthy controls.

Elevation of plasma 1-deoxy-sphingolipids in type 2 diabetes mellitus: a susceptibility to neuropathy?

PubMed

Dohrn, M F; Othman, A; Hirshman, S K; Bode, H; Alecu, I; Fähndrich, E; Karges, W; Weis, J; Schulz, J B; Hornemann, T; Claeys, K G

2015-05-01

Diabetic distal sensorimotor polyneuropathy (DSPN) is a frequent, disabling complication of diabetes mellitus. There is increasing evidence that sphingolipids play a role in insulin resistance and type 2 diabetes (T2DM). Whether neurotoxic 1-deoxy-sphingolipids are elevated in DSPN patients' plasma and whether levels correlate to the DSPN stage were examined. The plasma profile of 12 sphingoid bases in patients with DSPN and T2DM(n = 39) were cross-sectionally compared to other nerve disorders including chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 13), transthyretin-related familial amyloid polyneuropathy (FAP) (n = 10), amyotrophic lateral sclerosis (ALS) (n = 13) and small fibre neuropathy (n = 12) by liquid chromatography mass spectrometry. Correlations to the DSPN stage were additionally performed. Furthermore, the sphingoid base distribution in sural nerve specimens was measured in patients with DSPN (n = 6) compared to CIDP (n = 3). A significantly increased amount of 1-deoxy-sphingolipids [1-deoxy-sphinganine (0.11 ± 0.06 μmol/l), 1-deoxy-sphingosine (0.24 ± 0.16 μmol/l)] in patients with DSPN was observed compared to age-matched healthy controls (0.06 ± 0.03 μmol/l; 0.12 ± 0.05 μmol/l) and to the other groups. (Para)clinical parameters including sensory loss, neuropathic pain, weakness, vibration perception, nerve conduction velocity, sensory nerve action potentials (sural nerve) and duration of T2DM did not correlate with plasma 1-deoxy-sphingolipid levels, neither did the clinical stage according to the Dyck classification for DSPN. Sphingolipid levels in sural nerve biopsies showed no differences between DSPN and CIDP. Contrarily, patients with a small fibre neuropathy had decreased C₂₀-sphingosine plasma levels. 1-deoxy-sphingolipid plasma levels are significantly elevated in DSPN. They are already detectable in early disease stages but do not correlate with the clinical course. Further knowledge on 1-deoxy-sphingolipids might lead to a better pathophysiological understanding and future treatment options in DSPN. © 2015 EAN.

Neurophysiological aspects of peripheral neuropathies.

PubMed

MacKenzie, R A; Skuse, N F; Lethlean, A K

1976-01-01

1. Eighty-eight intrafascicular neural recordings were obtained in 10 normal subjects, 5 patients with axonal degeneration and 11 patients with demyelinating neuropathy. 2. Stimulus levels required for perception and fibre activation were higher in neuropathic subjects. Fibres transmitting touch perception had significantly lower conduction velocities in both patient groups, but were very much lower in the group with demyelinating neuropahty than the group with axonal degeneration. Maximum electrical stimulation evoked dispersed fibre responses in the axonal degeneration group and more dispersed, slowly conducting fibre potentials in the demyelinating group. In patients with hypertrophic Charcot-Marie-Tooth disorder, usually only a small group of slowly conducting low amplitude potentials was recorded. 3. Delivery of a train of supramaximal stimuli caused prolongation of latency and dispersion of fibre potentials in all microneurographic recordings. The changes were significantly greater in the axonal neuropathy group than in normals, and recovery was slower. The demyelinating neuropathies showed significantly greater changes than both the normal and the axonal neuropathy groups, and post-tetanic conduction slowing became even more marked after limb temperature was raised. 4. Surface SAP recordings showed normal refractory period in chronic axonal neuropathy but significant latency prolongation occurred in demyelinating neuropathy. 5. It is concluded that both receptor and nerve fibre abnormalities contribute to sensory dysfunction in degenerative and demyelinating neuropathies.

Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges

PubMed Central

De Col, Roberto; Messlinger, Karl; Carr, Richard W

2008-01-01

Axonal conduction velocity varies according to the level of preceding impulse activity. In unmyelinated axons this typically results in a slowing of conduction velocity and a parallel increase in threshold. It is currently held that Na+–K+-ATPase-dependent axonal hyperpolarization is responsible for this slowing but this has long been equivocal. We therefore examined conduction velocity changes during repetitive activation of single unmyelinated axons innervating the rat cranial meninges. In direct contradiction to the currently accepted postulate, Na+–K+-ATPase blockade actually enhanced activity-induced conduction velocity slowing, while the degree of velocity slowing was curtailed in the presence of lidocaine (10–300 μm) and carbamazepine (30–500 μm) but not tetrodotoxin (TTX, 10–80 nm). This suggests that a change in the number of available sodium channels is the most prominent factor responsible for activity-induced changes in conduction velocity in unmyelinated axons. At moderate stimulus frequencies, axonal conduction velocity is determined by an interaction between residual sodium channel inactivation following each impulse and the retrieval of channels from inactivation by a concomitant Na+–K+-ATPase-mediated hyperpolarization. Since the process is primarily dependent upon sodium channel availability, tracking conduction velocity provides a means of accessing relative changes in the excitability of nociceptive neurons. PMID:18096592

The course of the buccal nerve: relationships with the temporalis muscle during the prenatal period

PubMed Central

MÉRIDA-VELASCO, J. R.; RODRÍGUEZ-VÁZQUEZ, J. F.; CUADRA, C.; MÉRIDA-VELASCO, J. A.; JIMÉNEZ-COLLADO, J.

2001-01-01

The aim of this study was to describe the course of the buccal nerve and its relationships with the temporalis muscle during the prenatal period. Serial sections of 90 human fetal specimens ranging from 9 to 17 wk development were studied by light microscopy. Each fetal specimen was studied on both right and left sides, making a total of 180 cases for study. A 3-D reconstruction of the region analysed in one of the specimens was made. In 89 cases the buccal nerve was located medial to the temporalis muscle; in 73 cases it penetrated the muscle; in 15 cases it lay in a canal formed by the muscle fibres and was covered by fascia, and finally, in 3 cases it was a branch of the inferior alveolar nerve. The study has revealed that in a large number of cases the buccal nerve maintains an intimate association with the temporalis muscle. PMID:11327204

Hereditary sensory and autonomic neuropathy type I in a Chinese family: British C133W mutation exists in the Chinese.

PubMed

Bi, Hongyan; Gao, Yunying; Yao, Sheng; Dong, Mingrui; Headley, Alexander Peter; Yuan, Yun

2007-10-01

Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disorder of the peripheral nervous system characterized by marked progressive sensory loss, with variable autonomic and motor involvement. The HSAN I locus maps to chromosome 9q22.1-22.3 and is caused by mutations in the gene coding for serine palmitoyltransferase long chain base subunit 1 (SPTLC1). Sequencing in HSAN I families have previously identified mutations in exons 5, 6 and 13 of this gene. Here we report the clinical, electrophysiological and pathological findings of a proband in a Chinese family with HSAN I. The affected members showed almost typical clinical features. Electrophysiological findings showed an axonal, predominantly sensory, neuropathy with motor and autonomic involvement. Sural nerve biopsy showed loss of myelinated and unmyelinated fibers. SPTLC1 mutational analysis revealed the C133W mutation, a mutation common in British HSAN I families.

Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

PubMed Central

Namer, Barbara; Ørstavik, Kirstin; Schmidt, Roland; Mair, Norbert; Kleggetveit, Inge Petter; Zeidler, Maximillian; Martha, Theresa; Jorum, Ellen; Schmelz, Martin; Kalpachidou, Theodora; Kress, Michaela; Langeslag, Michiel

2017-01-01

The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons. PMID:28769867

Treatment with anti-TNF alpha protects against the neuropathy induced by the proteasome inhibitor bortezomib in a mouse model.

PubMed

Alé, Albert; Bruna, Jordi; Morell, Marta; van de Velde, Helgi; Monbaliu, Johan; Navarro, Xavier; Udina, Esther

2014-03-01

Bortezomib (BTZ), a proteasome inhibitor, is an effective anti-neoplastic drug used in the treatment of multiple myeloma and mantle cell lymphoma. However, it can induce a reversible peripheral neuropathy that may lead to treatment discontinuation. The mechanism through which BTZ exerts toxic effects in peripheral neurons is not clear. Release of proinflammatory cytokines after nerve damage can induce neurodegeneration, but the effects of BTZ on cytokine expression in neurons are unknown, although BTZ modulates the expression of cytokines, such as TNF-α and IL-6, in tumor cells. The aim of this study was to evaluate the expression and the role of these cytokines on the course of BTZ induced neuropathy in mice. IL-6, TNF-α, TGF-β1 and IL-1β were up-regulated in dorsal root ganglia but TNF-α and IL-6 increased faster and higher. Then, we studied the potential neuroprotective effect of selective antibodies anti-TNF-α and anti-IL-6 on the evolution of the neuropathy. Treatment with anti-TNF-α but not with anti-IL-6 significantly prevented the decrease of sensory nerve action potentials amplitude and the loss of myelinated and unmyelinated fibers. We conclude that monoclonal antibodies directed against TNF-α may be a suitable neuroprotective therapy against the neurotoxicity induced by BTZ. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study.

PubMed

Dalmolin, Gerusa D; Bannister, Kirsty; Gonçalves, Leonor; Sikandar, Shafaq; Patel, Ryan; Cordeiro, Marta do Nascimento; Gomez, Marcus Vinícius; Ferreira, Juliano; Dickenson, Anthony H

2017-07-01

Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Tx3-3 (0.3-100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

Peripheral neuropathy in children with type 1 diabetes.

PubMed

Louraki, M; Karayianni, C; Kanaka-Gantenbein, C; Katsalouli, M; Karavanaki, K

2012-10-01

Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Bone marrow-derived mesenchymal stem/stromal cells reverse the sensorial diabetic neuropathy via modulation of spinal neuroinflammatory cascades.

PubMed

Evangelista, Afrânio Ferreira; Vannier-Santos, Marcos André; de Assis Silva, Gessica Sabrina; Silva, Daniela Nascimento; Juiz, Paulo José Lima; Nonaka, Carolina Kymie Vasques; Dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira; Villarreal, Cristiane Flora

2018-06-22

Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here, we evaluated the therapeutic effects of MSC on spinal neuroinflammation, as well as on ultrastructural aspects of the peripheral nerve in DN-associated sensorial dysfunction. C57Bl/6 mice were treated with bone marrow-derived MSC (1 × 10 6 ), conditioned medium from MSC cultures (CM-MSC) or vehicle by endovenous route following the onset of streptozotocin (STZ)-induced diabetes. Paw mechanical and thermal nociceptive thresholds were evaluated by using von Frey filaments and Hargreaves test, respectively. Morphological and morphometric analysis of the sciatic nerve was performed by light microscopy and transmission electron microscopy. Mediators and markers of neuroinflammation in the spinal cord were measured by radioimmunoassay, real-time PCR, and immunofluorescence analyses. Diabetic mice presented behavioral signs of sensory neuropathy, mechanical allodynia, and heat hypoalgesia, which were completely reversed by a single administration of MSC or CM-MSC. The ultrastructural analysis of the sciatic nerve showed that diabetic mice exhibited morphological and morphometric alterations, considered hallmarks of DN, such as degenerative changes in axons and myelin sheath, and reduced area and density of unmyelinated fibers. In MSC-treated mice, these structural alterations were markedly less commonly observed and/or less pronounced. Moreover, MSC transplantation inhibited multiple parameters of spinal neuroinflammation found in diabetic mice, causing the reduction of activated astrocytes and microglia, oxidative stress signals, galectin-3, IL-1β, and TNF-α production. Conversely, MSC increased the levels of anti-inflammatory cytokines, IL-10, and TGF-β. The present study described the modulatory effects of MSC on spinal cord neuroinflammation in diabetic mice, suggesting new mechanisms by which MSC can improve DN.

Cell- and stage-specific localization of galectin-3, a β-galactoside-binding lectin, in a mouse model of experimental autoimmune encephalomyelitis.

PubMed

Itabashi, Tetsuya; Arima, Yasunobu; Kamimura, Daisuke; Higuchi, Kotaro; Bando, Yoshio; Takahashi-Iwanaga, Hiromi; Murakami, Masaaki; Watanabe, Masahiko; Iwanaga, Toshihiko; Nio-Kobayashi, Junko

2018-06-16

Multiple sclerosis (MS) is an autoimmune disease in which pathogenic T cells play an important role, and an experimental autoimmune encephalomyelitis (EAE) is used as an animal model of MS. Galectins are β-galactoside-binding lectins and involved in various physiological and pathological events. Among fifteen members of galectins, galectin-1, -8, and -9 play immunosuppressive roles in MS and EAE; however, the role of galectin-3 (gal-3) is complex and controversial. We examined expression of gal-3 in the spinal cord and nerve roots of EAE mice. No immunohistochemical signals were detected in naïve mice, whereas gal-3 appeared at lower lumbar levels of the spinal cord and nerve roots in EAE mice. In the spinal cord, gal-3-positive cells were activated microglia and/or infiltrating macrophages, which were round in shape and intensified for the lysosomal enzyme, cathepsin D, indicating elevated phagocytic activity. Gal-3-positive cells in the spinal cord were most abundant during the peak symptomatic period. In the recovery period, they disappeared from the spinal parenchyma but remained at moderate levels in the pia mater. Interestingly, gal-3-positive cells selectively appeared in ventral, but not dorsal, nerve roots running through the spinal canal, with expression peaking during the recovery period. In ventral nerve roots, the major cell type expressing gal-3 was a specific population of Schwann cells that surround unmyelinated axons and express the biosynthetic enzyme for l-serine, a potent neurotrophic amino acid. Gal-3 was also induced in Iba1/F4/80-positive macrophages, which engulf damaged myelin and axon debris. Thus, gal-3 is induced in distinct cell types that are engaged in removal of damaged axons and cell debris and axon regeneration and remyelination, suggesting a potential neuroprotective role of gal-3 in EAE mice. Copyright © 2018. Published by Elsevier Ltd.

Inhibitory motoneurons in arthropod motor control: organisation, function, evolution.

PubMed

Wolf, Harald

2014-08-01

Miniaturisation of somatic cells in animals is limited, for reasons ranging from the accommodation of organelles to surface-to-volume ratio. Consequently, muscle and nerve cells vary in diameters by about two orders of magnitude, in animals covering 12 orders of magnitude in body mass. Small animals thus have to control their behaviour with few muscle fibres and neurons. Hexapod leg muscles, for instance, may consist of a single to a few 100 fibres, and they are controlled by one to, rarely, 19 motoneurons. A typical mammal has thousands of fibres per muscle supplied by hundreds of motoneurons for comparable behavioural performances. Arthopods--crustaceans, hexapods, spiders, and their kin--are on average much smaller than vertebrates, and they possess inhibitory motoneurons for a motor control strategy that allows a broad performance spectrum despite necessarily small cell numbers. This arthropod motor control strategy is reviewed from functional and evolutionary perspectives and its components are described with a focus on inhibitory motoneurons. Inhibitory motoneurons are particularly interesting for a number of reasons: evolutionary and phylogenetic comparison of functional specialisations, evolutionary and developmental origin and diversification, and muscle fibre recruitment strategies.

Localization of nitric oxide synthase and NADPH-diaphorase in guinea pig and human cochleae.

PubMed

Ruan, R S; Leong, S K; Yeoh, K H

1997-01-01

The distributions of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and nitric oxide synthase (NOS) in mammalian cochlea were studied at light and electron microscope levels by NADPH-d histochemistry and brain NOS (bNOS) immunohistochemistry. The cochleae from 15 albino guinea pigs were perilymphatically fixed with 2% periodate-lysine-paraformaldehyde, decalcified in 10% EDTA and processed for light and electron microscopy after NADPH-d or NOS staining in frozen and vibratome sections respectively. One human cochlea was available for light microscope examination of NADPH-d or bNOS stained sections. Light microscope results revealed that type I neurons and nerve fibers of the spiral ganglion cells were labeled by bNOS immunohistochemistry as well as NADPH-d histochemistry in both guinea pig and human cochleae. At subcellular level, NADPH-d reaction product was localized in the mitochondria of the neuronal cytoplasm and axoplasm and in the cytoplasm of the vascular endothelium. The immunoreaction products of bNOS were evenly distributed in the neuronal cytoplasm and axoplasm. Myelinated and unmyelinated fibers in the intraganglionic spiral bundle and the inner spiral and inner radial fibers below the inner hair cells were labeled for bNOS. The nerve endings below the outer hair cells were not stained. NOS immunoreaction product was also found in the outer hair cells, Schwann cells of myelinated nerve fibers, Deiter's cells, pillar cells and the tympanic lamina cells. No difference was found in the staining pattern of both NADPH-d and NOS reaction products between human and guinea pig cochleae at the light microscope level. The results suggest that NO plays an important role in the maintenance of auditory function in the mammal.

In vivo confocal microscopic investigation of the cornea after autologous implantation of lenticules obtained through small incision lenticule extraction for treatment of hyperopia.

PubMed

Li, Meiyan; Li, Meng; Sun, Ling; Han, Tian; Ding, Lan; Xiang, Jun; Zhou, Xingtao

2018-01-01

To investigate re-innervation in the implanted lenticule, as well as changes to the cornea, after correcting hyperopia with an autologous implantation of a lenticule obtained through small incision lenticule extraction (SMILE). This study retrospectively analysed re-innervation in the implanted lenticule, as well as microscopic morphological changes in the corneal architecture of the recipient cornea in five patients (with myopia in one eye and hyperopia in the contralateral eye) who received SMILE in the myopic eye and femtosecond laser in situ keratomileusis (FS-LASIK) combined with lenticule implantation in the contralateral hyperopic eye. Re-innervation in the implanted lenticule, as well as microscopic morphological changes in corneal architecture, were evaluated by in vivo confocal microscopy. One patient was examined at postoperative week six, two were examined at postoperative month two, one was examined at postoperative month nine, and one was examined at postoperative month 12. Partial subbasal nerve fibre regeneration was detected in two patients (Case 4 who was examined at postoperative month nine and Case 5 who was examined at postoperative month 12). Regenerated and branched nerve fibres were detected in the implanted lenticule in Case 5 who was examined at postoperative month 12. Both the anterior and posterior interfaces showed an absence or decrease of keratocytes and the presence of small particles of various brightnesses. Keratocytes in the implanted lenticule presented abnormal morphology in size and shape after surgery in all treated eyes, but showed partial morphological recovery in two patients (Case 4 who was examined at postoperative month nine and Case 5 who was examined at postoperative month 12). These preliminary findings suggest that nerve fibres will regenerate into the implanted lenticule after autologous lenticule implantation. Keratocytes in lenticules demonstrated a gradual return to a normal morphology. © 2017 Optometry Australia.

Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers.

PubMed

Friberg, D; Gazelius, B; Hökfelt, T; Nordlander, B

1997-07-23

Habitual snoring precedes obstructive sleep apnea (OSA), but the pathophysiological mechanisms behind progression are still unclear. The patency of upper airways depends on a reflexogen mechanism reacting on negative intrapharyngeal pressure at inspiration, probably mediated by mucosal receptors, i.e., via afferent nerve endings. Such nerves contain a specific nerve protein, protein-gene product 9.5 (PGP 9.5) and in some cases substance P (SP) and calcitonin gene-related (CGRP). Biopsies of the soft palatial mucosa were obtained from non-smoking men ten OSA patients, 11 habitual snorers and 11 non-snoring controls. The specimens were immunohistochemically analyzed for PGP 9.5, SP and CGRP. As compared to controls, an increased number of PGP-, SP- and CGRP-immunoreactive nerves were demonstrated in the mucosa in 9/10 OSA patients and 4/11 snorers, in addition to varicose nerve endings in the papillae and epithelium. Using double staining methodology, it could be shown that SP- and CGRP-like immunoreactivities (LIs) often coexisted in these fibres, as did CGRP- and PGP 9.5-LIs. The increased density in sensory nerve terminals are interpreted to indicate an afferent nerve lesion. Our results support the hypothesis of a progressive neurogenic lesion as a contributory factor to the collapse of upper airways during sleep in OSA patients.

Nociception at the diabetic foot, an uncharted territory

PubMed Central

Chantelau, Ernst A

2015-01-01

The diabetic foot is characterised by painless foot ulceration and/or arthropathy; it is a typical complication of painless diabetic neuropathy. Neuropathy depletes the foot skin of intraepidermal nerve fibre endings of the afferent A-delta and C-fibres, which are mostly nociceptors and excitable by noxious stimuli only. However, some of them are cold or warm receptors whose functions in diabetic neuropathy have frequently been reported. Hence, it is well established by quantitative sensory testing that thermal detection thresholds at the foot skin increase during the course of painless diabetic neuropathy. Pain perception (nociception), by contrast, has rarely been studied. Recent pilot studies of pinprick pain at plantar digital skinfolds showed that the perception threshold was always above the upper limit of measurement of 512 mN (equivalent to 51.2 g) at the diabetic foot. However, deep pressure pain perception threshold at musculus abductor hallucis was beyond 1400 kPa (equivalent to 14 kg; limit of measurement) only in every fifth case. These discrepancies of pain perception between forefoot and hindfoot, and between skin and muscle, demand further study. Measuring nociception at the feet in diabetes opens promising clinical perspectives. A critical nociception threshold may be quantified (probably corresponding to a critical number of intraepidermal nerve fibre endings), beyond which the individual risk of a diabetic foot rises appreciably. Staging of diabetic neuropathy according to nociception thresholds at the feet is highly desirable as guidance to an individualised injury prevention strategy. PMID:25897350

Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise

PubMed Central

Gundersen, Kristian

2011-01-01

Muscle fibres have different properties with respect to force, contraction speed, endurance, oxidative/glycolytic capacity etc. Although adult muscle fibres are normally post-mitotic with little turnover of cells, the physiological properties of the pre-existing fibres can be changed in the adult animal upon changes in usage such as after exercise. The signal to change is mainly conveyed by alterations in the patterns of nerve-evoked electrical activity, and is to a large extent due to switches in the expression of genes. Thus, an excitation-transcription coupling must exist. It is suggested that changes in nerve-evoked muscle activity lead to a variety of activity correlates such as increases in free intracellular Ca2+ levels caused by influx across the cell membrane and/or release from the sarcoplasmatic reticulum, concentrations of metabolites such as lipids and ADP, hypoxia and mechanical stress. Such correlates are detected by sensors such as protein kinase C (PKC), calmodulin, AMP-activated kinase (AMPK), peroxisome proliferator-activated receptor δ (PPARδ), and oxygen dependent prolyl hydroxylases that trigger intracellular signaling cascades. These complex cascades involve several transcription factors such as nuclear factor of activated T-cells (NFAT), myocyte enhancer factor 2 (MEF2), myogenic differentiation factor (myoD), myogenin, PPARδ, and sine oculis homeobox 1/eyes absent 1 (Six1/Eya1). These factors might act indirectly by inducing gene products that act back on the cascade, or as ultimate transcription factors binding to and transactivating/repressing genes for the fast and slow isoforms of various contractile proteins and of metabolic enzymes. The determination of size and force is even more complex as this involves not only intracellular signaling within the muscle fibres, but also muscle stem cells called satellite cells. Intercellular signaling substances such as myostatin and insulin-like growth factor 1 (IGF-1) seem to act in a paracrine fashion. Induction of hypertrophy is accompanied by the satellite cells fusing to myofibres and thereby increasing the capacity for protein synthesis. These extra nuclei seem to remain part of the fibre even during subsequent atrophy as a form of muscle memory facilitating retraining. In addition to changes in myonuclear number during hypertrophy, changes in muscle fibre size seem to be caused by alterations in transcription, translation (per nucleus) and protein degradation. PMID:21040371

Investigation of the Expression of Myogenic Transcription Factors, microRNAs and Muscle-Specific E3 Ubiquitin Ligases in the Medial Gastrocnemius and Soleus Muscles following Peripheral Nerve Injury

PubMed Central

Wiberg, Rebecca; Jonsson, Samuel; Novikova, Liudmila N.; Kingham, Paul J.

2015-01-01

Despite surgical innovation, the sensory and motor outcome after a peripheral nerve injury remains incomplete. One contributing factor to the poor outcome is prolonged denervation of the target organ, leading to apoptosis of both mature myofibres and satellite cells with subsequent replacement of the muscle tissue with fibrotic scar and adipose tissue. In this study, we investigated the expression of myogenic transcription factors, muscle specific microRNAs and muscle-specific E3 ubiquitin ligases at several time points following denervation in two different muscles, the gastrocnemius (containing predominantly fast type fibres) and soleus (slow type) muscles, since these molecules may influence the degree of atrophy following denervation. Both muscles exhibited significant atrophy (compared with the contra-lateral sides) at 7 days following either a nerve transection or crush injury. In the crush model, the soleus muscle showed significantly increased muscle weights at days 14 and 28 which was not the case for the gastrocnemius muscle which continued to atrophy. There was a significantly more pronounced up-regulation of MyoD expression in the denervated soleus muscle compared with the gastrocnemius muscle. Conversely, myogenin was more markedly elevated in the gastrocnemius versus soleus muscles. The muscles also showed significantly contrasting transcriptional regulation of the microRNAs miR-1 and miR-206. MuRF1 and Atrogin-1 showed the highest levels of expression in the denervated gastrocnemius muscle. This study provides further insights regarding the intracellular regulatory molecules that generate and maintain distinct patterns of gene expression in different fibre types following peripheral nerve injury. PMID:26691660

Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs

PubMed Central

Mazzone, Stuart B; Mori, Nanako; Canning, Brendan J

2005-01-01

Cough initiated from the trachea and larynx in anaesthetized guinea-pigs is mediated by capsaicin-insensitive, mechanically sensitive vagal afferent neurones. Tachykinin-containing, capsaicin-sensitive C-fibres also innervate the airways and have been implicated in the cough reflex. Capsaicin-sensitive nerves act centrally and synergistically to modify reflex bronchospasm initiated by airway mechanoreceptor stimulation. The hypothesis that polymodal mechanoreceptors and capsaicin-sensitive afferent nerves similarly interact centrally to regulate coughing was addressed in this study. Cough was evoked from the tracheal mucosa either electrically (16 Hz, 10 s trains, 1–10 V) or by citric acid (0.001–2 m). Neither capsaicin nor bradykinin evoked a cough when applied to the trachea of anaesthetized guinea-pigs, but they substantially reduced the electrical threshold for initiating the cough reflex. The TRPV1 receptor antagonist capsazepine prevented the increased cough sensitivity induced by capsaicin. These effects of topically applied capsaicin and bradykinin were not due to interactions between afferent nerve subtypes within the tracheal wall or a direct effect on the cough receptors, as they were mimicked by nebulizing 1 mg ml−1 bradykinin into the lower airways and by microinjecting 0.5 nmol capsaicin into nucleus of the solitary tract (nTS). Citric acid-induced coughing was also potentiated by inhalation of bradykinin. The effects of tracheal capsaicin challenge on cough were mimicked by microinjecting substance P (0.5–5 nmol) into the nTS and prevented by intracerebroventricular administration (20 nmol h−1) of the neurokinin receptor antagonists CP99994 or SB223412. Tracheal application of these antagonists was without effect. C-fibre activation may thus sensitize the cough reflex via central mechanisms. PMID:16051625

β‐Endorphin, Met‐enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis

PubMed Central

Mousa, Shaaban A; Straub, Rainer H; Schäfer, Michael; Stein, Christoph

2007-01-01

Objective Intra‐articularly applied opioid agonists or antagonists modulate pain after knee surgery and in chronic arthritis. Therefore, the expression of β‐endorphin (END), Met‐enkephalin (ENK), and μ and δ opioid receptors (ORs) within synovium of patients with joint trauma (JT), osteoarthritis (OA) and rheumatoid arthritis (RA) were examined. Methods Synovial samples were subjected to double immunohistochemical analysis of opioid peptides with immune cell markers, and of ORs with the neuronal markers calcitonin gene‐related peptide (CGRP) and tyrosine hydroxylase (TH). Results END and ENK were expressed by macrophage‐like (CD68+) and fibroblast‐like (CD68−) cells within synovial lining layers of all disorders. In the sublining layers, END and ENK were mostly expressed by granulocytes in patients with JT, and by macrophages/monocytes, lymphocytes and plasma cells in those with OA and RA. Overall, END‐ and ENK‐immunoreactive (IR) cells were more abundant in patients with RA than in those with OA and JT. ORs were found on nerve fibres and immune cells in all patients. OR‐IR nerve fibres were significantly more abundant in patients with RA than in those with OA and JT. μORs and δORs were coexpressed with CGRP but not with TH. Conclusions Parallel to the severity of inflammation, END and ENK in immune cells and their receptors on sensory nerve terminals are more abundant in patients with RA than in those with JT and OA. These findings are consistent with the notion that, with prolonged and enhanced inflammation, the immune and peripheral nervous systems upregulate sensory nerves expressing ORs and their ligands to counterbalance pain and inflammation. PMID:17324971

Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy

PubMed Central

Panaite, Petrica-Adrian; Kuntzer, Thierry; Gourdon, Geneviève; Lobrinus, Johannes Alexander; Barakat-Walter, Ibtissam

2013-01-01

SUMMARY Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs) and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding mechanisms of respiratory deficiency should guide pharmaceutical and clinical research towards better therapy for the respiratory deficits associated with DM1. PMID:23180777

[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.

The role of precisely matching fascicles in the quick recovery of nerve function in long peripheral nerve defects

PubMed Central

Yan, Liwei; Yao, Zhi; Lin, Tao; Zhu, Qingtang; Qi, Jian; Gu, Liqiang; Fang, Jintao; Zhou, Xiang

2017-01-01

Peripheral nerve injury therapy in the clinic remains less than satisfactory. The gold standard of treatment for long peripheral nerve defects is autologous nerve grafts; however, numerous clinical complications are associated with this treatment. As tissue engineering has developed, tissue-engineered nerve grafts (TENGs) have shown potential applications as alternatives to autologous nerve grafts. To verify the important role of the biomimetic pathway of fascicle design in TENGs, we designed an animal model to study the role of the precise matching of fascicles in the effectiveness of nerve function recovery. 24 Sprague-Dawley rats were divided randomly into three groups (eight/group) that corresponded to 100% fascicle matching (100%FM), 50%FM and 0%FM. We selected Sprague–Dawley rat long-gap (15 mm) sciatic nerve defects. In the 6 weeks after surgery, we found that the 100%FM group showed the most effective functional recovery among the three groups. The 100%FM group showed better functional recovery on the basis of the sciatic functional index than the 50%FM and 0%FM groups. According to histological evaluation, the 100%FM group showed more regenerating nerve fibres. Moreover, in terms of the prevention of muscle atrophy, the 100%FM group showed excellent physiological outcomes. The 100%FM as tissue-engineered scaffolds can enhance nerve regeneration and effective functional recovery after the repair of large nerve defects. The results of this study provide a theoretical basis for future TENG designs including biomimetic fascicle pathways for repairing long nerve defects. PMID:28914740

Small fibre neuropathy in mitochondrial diseases explored with sudoscan.

PubMed

Luigetti, Marco; Primiano, Guido; Cuccagna, Cristina; Bernardo, Daniela; Sauchelli, Donato; Vollono, Catello; Servidei, Serenella

2018-06-01

Polyneuropathy in mitochondrial diseases (MDs) is relatively common and widely investigated, but few data are instead reported about small fibres involvement. In order to investigate the involvement of small fibres in MDs we performed extensive neurophysiological test (nerve conduction studies; sympathetic skin response; sudoscan) in 27 patients with genetic diagnosis of MD (7 m.3243A > G; 4 m.8344A > G; 9 single mtDNA deletion; 7 multiple mtDNA deletions). NCS showed a polyneuropathy in 11/27 cases (41%). The incidence was very high in POLG1 (100%), m.8344A > G (75%) and m.3243A > G (43%), while only 11% of patients with single deletion had evidence of large fibres involvement. Sympathetic skin response was abnormal only in three patients (one progressive external ophthalmoplegia with single mtDNA deletion; one patient with m.3243A > G mutation; one patient with POLG1 mutation). Sudoscan revealed the presence of an autonomic small fibres dysfunction in 9/27 cases (33%), most of them (7/9) carrying a single mtDNA deletion. Sudoscan data were also confirmed in a sub-group of patients by laser evoked potentials study. Considering only patients with single mtDNA deletion 7/9 (78%) showed abnormal results at sudoscan. Small fibre neuropathy is another feature to investigate in mitochondrial diseases and seems specifically associated with the presence of single mtDNA deletion. The correct identification through specific neurophysiological tests of small fibres involvement in MDs represents another tile in this challenging diagnosis. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Histopathological examination of nerve samples from pure neural leprosy patients: obtaining maximum information to improve diagnostic efficiency.

PubMed

Antunes, Sérgio Luiz Gomes; Chimelli, Leila; Jardim, Márcia Rodrigues; Vital, Robson Teixeira; Nery, José Augusto da Costa; Corte-Real, Suzana; Hacker, Mariana Andréa Vilas Boas; Sarno, Euzenir Nunes

2012-03-01

Nerve biopsy examination is an important auxiliary procedure for diagnosing pure neural leprosy (PNL). When acid-fast bacilli (AFB) are not detected in the nerve sample, the value of other nonspecific histological alterations should be considered along with pertinent clinical, electroneuromyographical and laboratory data (the detection of Mycobacterium leprae DNA with polymerase chain reaction and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a possible or probable PNL diagnosis. Three hundred forty nerve samples [144 from PNL patients and 196 from patients with non-leprosy peripheral neuropathies (NLN)] were examined. Both AFB-negative and AFB-positive PNL samples had more frequent histopathological alterations (epithelioid granulomas, mononuclear infiltrates, fibrosis, perineurial and subperineurial oedema and decreased numbers of myelinated fibres) than the NLN group. Multivariate analysis revealed that independently, mononuclear infiltrate and perineurial fibrosis were more common in the PNL group and were able to correctly classify AFB-negative PNL samples. These results indicate that even in the absence of AFB, these histopathological nerve alterations may justify a PNL diagnosis when observed in conjunction with pertinent clinical, epidemiological and laboratory data.

Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.

PubMed

Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A

1992-10-01

The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened.

Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview.

PubMed

Navarro, Xavier

2016-02-01

Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutic strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibres, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and also to perform morphological studies of the injured nerve and the reinnervated targets. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Todd, Faraday and the electrical basis of brain activity.

PubMed

Reynolds, Edward

2007-10-01

The origins of our understanding of brain electricity and electrical discharges in epilepsy can be traced to Robert Bentley Todd (1809-60). Todd was influenced by his contemporary in London, Michael Faraday (1791-1867), who in the 1830 s and 1840 s was laying the foundations of our modern understanding of electromagnetism. Todd's concept of nervous polarity, generated in nerve vesicles and transmitted in nerve fibres (neurons in later terminology), was confirmed a century later by the Nobel Prize-winning work of Hodgkin and Huxley, who demonstrated the ionic basis of neuro-transmission, involving the same ions which had had been discovered by Faraday's mentor, Sir Humphry Davy (1778-1829).

Neuromuscular block after intra-arterially injected acetylcholine

PubMed Central

Pinelli, P.; Tonali, P.; Gambi, D.

1973-01-01

It has been suggested that the effect of ACTH in myasthenia gravis may be ascribed to an action involving neuromuscular transmission which favours repolarization processes, with a tendency towards hyperpolarization of the membranes of muscle fibres and motor nerve endings. A similar mechanism has been postulated for the action of ACTH in epilepsy (Klein, 1970). A direct or indirect action on nerve membrane would interfere with depolarization. There is evidence of raised concentration of intracellular potassium and increased outflow of sodium ions which would cause hyperpolarization of the membrane. This paper studies the effect of ACTH on the late block of neuromuscular transmission caused by acetylcholine (ACTH). Images PMID:4350704

Thulium fibre laser nerve stimulation and its application in human pain research

NASA Astrophysics Data System (ADS)

Warnaby, Catherine E.

Experimental pain induction, in combination with psychophysical and functional imaging techniques, allows the controlled study of the mechanisms, pathways and brain areas involved in the processing of noxious stimuli. Laser nerve stimulation provides an excellent stimulus that selectively activates the Adelta and C nociceptors with only low concurrent activity in the warmth system. Thulium fibre laser systems, operating near 2mum, offer several advantages over other pain stimulators including the CO[2] and Tm:YAG laser systems. These advantages include direct absorption at the location of the nociceptors, reduced likelihood of tissue damage, improved compatibility with fMRI, and wavelength tunability. The main aims of the thesis were to apply an initial thulium fibre laser system to pain activation studies in healthy subjects and confirm the potential advantages. A 1D finite difference photothermal model confirmed that thulium fibre laser radiation is absorbed throughout the expected location of the nociceptors and produces a lower surface temperature than CO[2] radiation. In order to produce a temperature rise of 9°C at 150mum, thulium radiation induces a surface temperature rise of 12°C compared to 21°C surface temperature rise using CO[2] radiation. The use of thulium fibre radiation greatly reduces the likelihood of tissue damage and first-degree burns when compared to CO[2] radiation. The spatial temperature gradient and the surface temperature rise were also found to be strongly dependent on the thulium fibre laser emission wavelength, which implies that wavelength tuning may be used to obtain the optimum stimulus wavelength in the 2mum region. The 5W initial fibre laser system was fully characterised before application to human pain studies and was shown to have excellent reproducibility of the stimulus parameters, with short-term and long-term deviations of the pulse energy of 5% and 8% of the mean respectively. The thulium fibre laser emits radiation over a 38nm wavelength range from 2.006-2.044mum. The initial system was used successfully to elicit painful sensations and laser evoked potentials (LEPs), which showed the expected dependence on the laser stimulus parameters. In agreement with the modelled results, beam diameters from 5-8mm for a 150ms pulse duration were found to elicit painful responses while minimising tissue damage. Psychophysical assessment of the pain threshold energy and energy density in ten volunteers, using the modified staircase technique and the method of constant stimuli, also showed the expected dependence on the laser beam diameter over this range. The topographical distribution of the LEPs elicited by the thulium fibre laser and a CO[2] pain stimulator were found to be very similar. However, statistically significant differences in the peak latencies of the LEP components were observed. The peak latency of the N2, P2 and P3 components elicited by the thulium fibre laser were found to be longer by 44ms, 52ms and 78ms respectively than those elicited by the CO[2] laser across five volunteers. These latency differences are believed to be due to the difference in beam diameter of the two stimuli, which produces an increase in local spatial summation for the CO[2] laser stimuli. The effectiveness of the thulium fibre laser as a controlled pain stimulator for human pain research has been confirmed. Using the current thulium fibre laser stimulation system, the optimum stimulus parameters are provided by a beam diameter of 6mm and a pulse duration of 150ms. However, further application of the current system to human pain research is limited by the available output power and the delivery of the thulium radiation to the subject. Suggestions are made for further work using an improved thulium fibre laser system with an increased output power of 20W, optical fibre delivery and wavelength tuning.

Influence of atypical retardation pattern on the peripapillary retinal nerve fibre distribution assessed by scanning laser polarimetry and optical coherence tomography.

PubMed

Schrems, W A; Laemmer, R; Hoesl, L M; Horn, F K; Mardin, C Y; Kruse, F E; Tornow, R P

2011-10-01

To investigate the influence of atypical retardation pattern (ARP) on the distribution of peripapillary retinal nerve fibre layer (RNFL) thickness measured with scanning laser polarimetry in healthy individuals and to compare these results with RNFL thickness from spectral domain optical coherence tomography (OCT) in the same subjects. 120 healthy subjects were investigated in this study. All volunteers received detailed ophthalmological examination, GDx variable corneal compensation (VCC) and Spectralis-OCT. The subjects were divided into four subgroups according to their typical scan score (TSS): very typical with TSS=100, typical with 99 ≥ TSS ≥ 91, less typical with 90 ≥ TSS ≥ 81 and atypical with TSS ≤ 80. Deviations from very typical normal values were calculated for 32 sectors for each group. There was a systematic variation of the RNFL thickness deviation around the optic nerve head in the atypical group for the GDxVCC results. The highest percentage deviation of about 96% appeared temporal with decreasing deviation towards the superior and inferior sectors, and nasal sectors exhibited a deviation of 30%. Percentage deviations from very typical RNFL values decreased with increasing TSS. No systematic variation could be found if the RNFL thickness deviation between different TSS-groups was compared with the OCT results. The ARP has a major impact on the peripapillary RNFL distribution assessed by GDx VCC; thus, the TSS should be included in the standard printout.

Correlation between central corneal thickness and visual field defects, cup to disc ratio and retinal nerve fiber layer thickness in primary open angle glaucoma patients.

PubMed

Sarfraz, Muhammad Haroon; Mehboob, Mohammad Asim; Haq, Rana Intisar Ul

2017-01-01

To evaluate the correlation between Central Corneal Thickness (CCT) and Visual Field (VF) defect parameters like Mean Deviation (MD) and Pattern Standard Deviation (PSD), Cup-to-Disc Ratio (CDR) and Retinal Nerve Fibre Layer Thickness (RNFL-T) in Primary Open-Angle Glaucoma (POAG) patients. This cross sectional study was conducted at Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi from September 2015 to September 2016. Sixty eyes of 30 patients with diagnosed POAG were analysed. Correlation of CCT with other variables was studied. Mean age of study population was 43.13±7.54 years. Out of 30 patients, 19 (63.33%) were males and 11 (36.67%) were females. Mean CCT, MD, PSD, CDR and RNFL-T of study population was 528.57±25.47µm, -9.11±3.07, 6.93±2.73, 0.63±0.13 and 77.79±10.44µm respectively. There was significant correlation of CCT with MD, PSD and CDR (r=-0.52, p<0.001; r=-0.59, p<0.001;r=-0.41, p=0.001 respectively). The correlation of CCT with RNFL-T was not statistically significant (r=-0.14, p=0.284). Central corneal thickness had significant correlation with visual field parameters like mean deviation and pattern standard deviation, as well as with cup-to-disc ratio. However, central corneal thickness had no significant relationship with retinal nerve fibre layer thickness.

Neuroanatomy and neurophysiology related to sexual dysfunction in male neurogenic patients with lesions to the spinal cord or peripheral nerves.

PubMed

Everaert, K; de Waard, W I Q; Van Hoof, T; Kiekens, C; Mulliez, T; D'herde, C

2010-03-01

Review article. The neuroanatomy and physiology of psychogenic erection, cholinergic versus adrenergic innervation of emission and the predictability of outcome of vibration and electroejaculation require a review and synthesis. University Hospital Belgium. We reviewed the literature with PubMed 1973-2008. Erection, emission and ejaculation are separate phenomena and have different innervations. It is important to realize, which are the afferents and efferents and where the motor neuron of the end organ is located. When interpreting a specific lesion it is important to understand if postsynaptic fibres are intact or not. Afferents of erection, emission and ejaculation are the pudendal nerve and descending pathways from the brain. Erection is cholinergic and NO-mediated. Emission starts cholinergically (as a secretion) and ends sympathetically (as a contraction). Ejaculation is mainly adrenergic and somatic. For vibratory-evoked ejaculation, the reflex arch must be complete; for electroejaculation, the postsynaptic neurons (paravertebral ganglia) must be intact. Afferents of erection, emission and ejaculation are the pudendal nerve and descending pathways from the brain. Erection is cholinergic and NO-mediated. Emission starts cholinergically (as a secretion) and ends sympathetically (as a contraction). Ejaculation is mainly adrenergic and somatic. In neurogenic disease, a good knowledge of neuroanatomy and physiology makes understanding of sexual dysfunction possible and predictable. The minimal requirement for the success of penile vibration is a preserved reflex arch and the minimal requirement for the success of electroejaculation is the existence of intact post-ganglionic fibres.

Diuretic‐sensitive electroneutral Na+ movement and temperature effects on central axons

PubMed Central

Kanagaratnam, Meneka; Pendleton, Christopher; Souza, Danilo Almeida; Pettit, Joseph; Howells, James

2017-01-01

Key points Optic nerve axons get less excitable with warming.F‐fibre latency does not shorten at temperatures above 30°C.Action potential amplitude falls when the Na+‐pump is blocked, an effect speeded by warming.Diuretics reduce the rate of action potential fall in the presence of ouabain.Our data are consistent with electroneutral entry of Na+ occurring in axons and contributing to setting the resting potential. Abstract Raising the temperature of optic nerve from room temperature to near physiological has effects on the threshold, refractoriness and superexcitability of the shortest latency (fast, F) nerve fibres, consistent with hyperpolarization. The temperature dependence of peak impulse latency was weakened at temperatures above 30°C suggesting a temperature‐sensitive process that slows impulse propagation. The amplitude of the supramaximal compound action potential gets larger on warming, whereas in the presence of bumetanide and amiloride (blockers of electroneutral Na+ movement), the action potential amplitude consistently falls. This suggests a warming‐induced hyperpolarization that is reduced by blocking electroneutral Na+ movement. In the presence of ouabain, the action potential collapses. This collapse is speeded by warming, and exposure to bumetanide and amiloride slows the temperature‐dependent amplitude decline, consistent with a warming‐induced increase in electroneutral Na+ entry. Blocking electroneutral Na+ movement is predicted to be useful in the treatment of temperature‐dependent symptoms under conditions with reduced safety factor (Uhthoff's phenomenon) and provide a route to neuroprotection. PMID:28213919

Inhibitory effect of troglitazone on diabetic neuropathy in streptozotocin-induced diabetic rats.

PubMed

Qiang, X; Satoh, J; Sagara, M; Fukuzawa, M; Masuda, T; Sakata, Y; Muto, G; Muto, Y; Takahashi, K; Toyota, T

1998-11-01

Free-radical scavengers and inhibitors of tumour necrosis factor-alpha (TNF-alpha) such as N-acetylcysteine and pentoxifylline have been shown to inhibit the development of peripheral neuropathy in streptozotocin(STZ)-induced diabetic rats. In this study we examined the effect of troglitazone, an anti-diabetic thiazolidinedione, on diabetic neuropathy, since it also is a free-radical scavenger and a TNF-alpha inhibitor. Rats were fed powder chow mixed with troglitazone at 0.5% and 0.125% ad libitum. Although blood glucose concentrations were remarkably higher and body weight lower in diabetic than in nondiabetic rats, troglitazone had no effect on these throughout the 24-week experiment. Serum lipoperoxide concentrations, tibial nerve lipoperoxide content and serum TNF-alpha activity induced by lipopolysaccharide was increased in diabetic rats, but inhibited in troglitazone-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve slowed in diabetic rats, compared with that in nondiabetic rats. On the other hand, the slowed MNCV was (p < 0.05-0.01) inhibited after weeks 12 and 16 of the experiment in diabetic rats treated with high and low doses of troglitazone, respectively. Morphometric analysis showed that troglitazone suppressed the decrease of the myelinated fibre area (p < 0.05), axon/myelin ratio (p < 0.01) and fascicular area (p < 0.05) and suppressed the increase of myelinated fibre density (p < 0.001) in diabetic rats. These results indicate that troglitazone has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats irrespective of blood glucose concentrations.

A history of the optic nerve and its diseases.

PubMed

Reeves, C; Taylor, D

2004-11-01

We will trace the history of ideas about optic nerve anatomy and function in the Western world from the ancient Greeks to the early 20th century and show how these influenced causal theories of optic nerve diseases. Greek and Roman humoral physiology needed a hollow optic nerve, the obstruction of which prevented the flow of visual spirit to and from the brain and resulted in blindness. Medieval physicians understood that the presence of a fixed dilated pupil indicated optic nerve obstruction, preventing the passage of visual spirit, and that cataract surgery in such cases would not restore sight. During the Renaissance, the organ of vision was transferred from the lens to the optic nerve, which was generally believed to be on the axis of the eye. The acuity of central vision (at the optic disc) was explained by the concentration of visual spirit where the optic nerve met the retina. The growth of anatomy and influence of mechanical philosophy from the 17th century led to visual spirit being replaced with the concept of nerve force, which later became associated with electricity travelling along nerve fibres. This coincided with discourse about the nature of the nervous system and a shift in orientation from understanding illness holistically in terms of an individual's humoral imbalance to the concept of organ-based diseases. Both the microscope and the ophthalmoscope allowed visualisation of the optic nerve, but problems of interpretation persisted until conceptual transformations in medical science were made.

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

PubMed

Schild, John H; Kunze, Diana L

2012-12-24

Voltage gated ion channels (VGC) make possible the frequency coding of arterial pressure and the neurotransmission of this information along myelinated and unmyelinated fiber pathways. Although many of the same VGC isoforms are expressed in both fiber types, it is the relative expression of each that defines the unique discharge properties of myelinated A-type and unmyelinated C-type baroreceptors. For example, the fast inward Na⁺ current is a major determinant of the action potential threshold and the regenerative transmembrane current needed to sustain repetitive discharge. In A-type baroreceptors the TTX-sensitive Na(v)1.7 VGC contributes to the whole cell Na⁺ current. Na(v)1.7 is expressed at a lower density in C-type neurons and in conjunction with TTX-insensitive Na(v)1.8 and Na(v)1.9 VGC. As a result, action potentials of A-type neurons have firing thresholds that are 15-20 mV more negative and upstroke velocities that are 5-10 times faster than unmyelinated C-type neurons. A more depolarized threshold in conjunction with a broader complement of non-inactivating K(V) VGC subtypes produces C-type action potentials that are 3-4 times longer in duration than A-type neurons and at markedly lower levels of cell excitability. Unmyelinated baroreceptors also express KCa1.1 which provides approximately 25% of the total outward K⁺ current. KCa1.1 plays a critically important role in shaping the action potential profile of C-type neurons and strongly impacts neuronal excitability. A-type neurons do not functionally express the KCa1.1 channel despite having a whole cell Ca(V) current quite similar to that of C-type neurons. As a result, A-type neurons do not have the frequency-dependent braking forces of KCa1.1. Lack of a KCa current and only a limited complement of non-inactivating K(V) VGC in addition to a hyperpolarization activated HCN1 current that is nearly 10 times larger than in C-type neurons leads to elevated levels of discharge in A-type neurons, a hallmark of myelinated baroreceptors. Interestingly, HCN2 and HCN4 expression levels are comparable in both fiber types. Collectively, such apportion of VGC constrains the neural coding of myelinated A-type baroreceptors to low threshold, high frequency, high fidelity discharge but with a limited capacity for neuromodulation of afferent bandwidth. Unmyelinated C-type baroreceptors require greater depolarizing forces for spike initiation and have a low frequency discharge profile that is often poorly correlated with the physiological stimulus. But the complement of VGC in C-type neurons provides far greater capacity for neuromodulation of cell excitability than can be obtained from A-type baroreceptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Serotonin modulates substance P-induced plasma extravasation and vasodilatation in rat skin by an action through capsaicin-sensitive primary afferent nerves.

PubMed

Khalil, Z; Helme, R D

1990-09-17

Using a blister model of inflammation in the rat hind footpad, the present study was undertaken to examine the ability of serotonin (5-HT) to modulate an inflammatory reaction manifested as plasma extravasation and vasodilatation induced by the neuropeptide substance P (SP). In addition, the role of primary afferent sensory nerve fibres in these modulatory effects was studied in capsaicin pretreated rats. Using a protocol of simultaneous perfusion of amine and peptide over the blister base, no major modulatory effect was observed. On the other hand, using a protocol of sequential perfusion, 5-HT was found to extend the plasma extravasation and vasodilatation responses to SP. 5-HT maintained the plasma extravasation response to SP after cessation of stimulation (during the post-stimulation period). On the other hand, it extended the vasodilatation response to SP during the actual stimulation period by preventing the occurrence of tachyphylaxis. These modulatory effects were absent in capsacin-pretreated rats. The present study provides evidence for the first time in vivo to suggest that serotonin can modulate an inflammatory response to SP via a mechanism that involves capsaicin-sensitive sensory fibres.

Focal myositis: A review.

PubMed

Devic, P; Gallay, L; Streichenberger, N; Petiot, P

2016-11-01

Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK. Copyright © 2016 Elsevier B.V. All rights reserved.

Pulse-dose radiofrequency treatment in pain management-initial experience.

PubMed

Ojango, Christine; Raguso, Mario; Fiori, Roberto; Masala, Salvatore

2018-05-01

Radiofrequency procedures have been used for treating various chronic pain conditions for decades. These minimally invasive percutaneous treatments employ an alternating electrical current with oscillating radiofrequency wavelengths to eliminate or alter pain signals from the targeted site. The aim of the continuous radiofrequency procedure is to increase the temperature sufficiently to create an irreversible thermal lesion on nerve fibres and thus permanently interrupt pain signals. The pulsed radiofrequency procedure utilises short pulses of radiofrequency current with intervals of longer pauses to avert a temperature increase to the level of permanent tissue damage. The goal of these pulses is to alter the processing of pain signals, but to avoid relevant structural damage to nerve fibres, as seen in the continuous radiofrequency procedure. The pulse-dose radiofrequency procedure is a technical improvement of the pulsed radiofrequency technique in which the delivery mode of the current is adapted. During the pulse-dose radiofrequency procedure thermal damage is avoided. In addition, the amplitude and width of the consecutive pulses are kept the same. The method ensures that each delivered pulse keeps the same characteristics and therefore the dose is similar between patients. The current review outlines the pulse-dose radiofrequency procedure and presents our institution's chronic pain management studies.

Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage.

PubMed

Hood, D C; Harizman, N; Kanadani, F N; Grippo, T M; Baharestani, S; Greenstein, V C; Liebmann, J M; Ritch, R

2007-07-01

To assess the accuracy of optical coherence tomography (OCT) in detecting damage to a hemifield, patients with hemifield defects confirmed on both static automated perimetry (SAP) and multifocal visual evoked potentials (mfVEP) were studied. Eyes of 40 patients with concomitant SAP and mfVEP glaucomatous loss and 25 controls underwent OCT retinal nerve fibre layer (RNFL), mfVEP and 24-2 SAP tests. For the mfVEP and 24-2 SAP, a hemifield was defined as abnormal based upon cluster criteria. On OCT, a hemifield was considered abnormal if one of the five clock hour sectors (3 and 9 o'clock excluded) was at <1% (red) or two were at <5% (yellow). Seventy seven (43%) of the hemifields were abnormal on both mfVEP and SAP tests. The OCT was abnormal for 73 (95%) of these. Only 1 (1%) of the 100 hemifields of the controls was abnormal on OCT. Sensitivity/specificity (one eye per person) was 95/98%. The OCT RNFL test accurately detects abnormal hemifields confirmed on both subjective and objective functional tests. Identifying abnormal hemifields with a criterion of 1 red (1%) or 2 yellow (5%) clock hours may prove useful in clinical practice.

Mechanobiological dysregulation of the epidermis and dermis in skin disorders and in degeneration

PubMed Central

Ogawa, Rei; Hsu, Chao-Kai

2013-01-01

During growth and development, the skin expands to cover the growing skeleton and soft tissues by constantly responding to the intrinsic forces of underlying skeletal growth as well as to the extrinsic mechanical forces from body movements and external supports. Mechanical forces can be perceived by two types of skin receptors: (1) cellular mechanoreceptors/mechanosensors, such as the cytoskeleton, cell adhesion molecules and mechanosensitive (MS) ion channels, and (2) sensory nerve fibres that produce the somatic sensation of mechanical force. Skin disorders in which there is an abnormality of collagen [e.g. Ehlers–Danlos syndrome (EDS)] or elastic (e.g. cutis laxa) fibres or a malfunction of cutaneous nerve fibres (e.g. neurofibroma, leprosy and diabetes mellitus) are also characterized to some extent by deficiencies in mechanobiological processes. Recent studies have shown that mechanotransduction is crucial for skin development, especially hemidesmosome maturation, which implies that the pathogenesis of skin disorders such as bullous pemphigoid is related to skin mechanobiology. Similarly, autoimmune diseases, including scleroderma and mixed connective tissue disease, and pathological scarring in the form of keloids and hypertrophic scars would seem to be clearly associated with the mechanobiological dysfunction of the skin. Finally, skin ageing can also be considered as a degenerative process associated with mechanobiological dysfunction. Clinically, a therapeutic strategy involving mechanoreceptors or MS nociceptor inhibition or acceleration together with a reduction or augmentation in the relevant mechanical forces is likely to be successful. The development of novel approaches such as these will allow the treatment of a broad range of cutaneous diseases. PMID:23672502

Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

PubMed Central

Anand, P.; Bley, K.

2011-01-01

Summary Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies. PMID:21852280

Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea-pig airways.

PubMed Central

Ricco, M M; Kummer, W; Biglari, B; Myers, A C; Undem, B J

1996-01-01

1. The present study addressed the hypothesis that jugular and nodose vagal ganglia contain the somata of functionally and anatomically distinct airway afferent fibres. 2. Anatomical investigations were performed by injecting guinea-pig airways with the neuronal tracer Fast Blue. The animals were killed 7 days later, and the ganglia were removed and immunostained with antisera against substance P (SP) and neurofilament protein (NF). In the nodose ganglion, NF-immunoreactive neurones accounted for about 98% of the Fast Blue-labelled cells while in the jugular ganglion they accounted for approximately 48%. SP and NF immunoreactivity was never (n = 100) observed in the same cell suggesting that the antisera labelled distinct populations. 3. Electrophysiological investigations were performed using an in vitro guinea-pig tracheal and bronchial preparation with intact afferent vagal pathways, including nodose and jugular ganglia. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in either ganglion. 4. The nodose ganglion contained the somata of mainly fast-conducting tracheal A delta fibres whereas the jugular ganglion contained equal numbers of C fibre and A delta fibre tracheal afferent somata. The nodose A delta neurones adapted rapidly to mechanical stimulation, had relatively low mechanical thresholds, were not activated by capsaicin and adapted rapidly to a hyperosmotic stimulus. By contrast, jugular A delta and C fibres adapted slowly to mechanical stimulation, were often activated by capsaicin, had higher mechanical thresholds and displayed a slow adaptation to a hyperosmotic stimulus. 5. The anatomical, physiological and pharmacological data provide evidence to support the contention that the vagal ganglionic source of the fibre supplying the airways ultimately dictates its neurochemical and physiological phenotype. Images Figure 1 PMID:8910234

Cutaneous reflexes in small muscles of the hand

PubMed Central

Caccia, M. R.; McComas, A. J.; Upton, A. R. M.; Blogg, T.

1973-01-01

A study has been made of the responses of motoneurones innervating small muscles of the hand to electrical and mechanical stimulation of the skin. Both excitatory and inhibitory effects could be observed in the same muscle after a single stimulus to a given area of skin. The earliest excitatory and inhibitory responses are probably mediated by group III and the smaller group II afferent nerve fibres. A later inhibition results from activity in the larger group II fibres which are connected to cutaneous mechanoreceptors, especially those in the tips of the fingers and thumb. This late inhibitory reflex may operate through the fusimotor system. The possible roles of these reflexes are discussed in relation to previous investigations in man and the cat. PMID:4272546

Reorganization of the human central nervous system.

PubMed

Schalow, G; Zäch, G A

2000-10-01

The key strategies on which the discovery of the functional organization of the central nervous system (CNS) under physiologic and pathophysiologic conditions have been based included (1) our measurements of phase and frequency coordination between the firings of alpha- and gamma-motoneurons and secondary muscle spindle afferents in the human spinal cord, (2) knowledge on CNS reorganization derived upon the improvement of the functions of the lesioned CNS in our patients in the short-term memory and the long-term memory (reorganization), and (3) the dynamic pattern approach for re-learning rhythmic coordinated behavior. The theory of self-organization and pattern formation in nonequilibrium systems is explicitly related to our measurements of the natural firing patterns of sets of identified single neurons in the human spinal premotor network and re-learned coordinated movements following spinal cord and brain lesions. Therapy induced cell proliferation, and maybe, neurogenesis seem to contribute to the host of structural changes during the process of re-learning of the lesioned CNS. So far, coordinated functions like movements could substantially be improved in every of the more than 100 patients with a CNS lesion by applying coordination dynamic therapy. As suggested by the data of our patients on re-learning, the human CNS seems to have a second integrative strategy for learning, re-learning, storing and recalling, which makes an essential contribution of the functional plasticity following a CNS lesion. A method has been developed by us for the simultaneous recording with wire electrodes of extracellular action potentials from single human afferent and efferent nerve fibres of undamaged sacral nerve roots. A classification scheme of the nerve fibres in the human peripheral nervous system (PNS) could be set up in which the individual classes of nerve fibres are characterized by group conduction velocities and group nerve fibre diameters. Natural impulse patterns of several identified single afferent and efferent nerve fibres (motoneuron axons) were extracted from multi-unit impulse patterns, and human CNS functions could be analyzed under physiologic and pathophysiologic conditions. With our discovery of premotor spinal oscillators it became possible to judge upon CNS neuronal network organization based on the firing patterns of these spinal oscillators and their driving afferents. Since motoneurons fire occasionally for low activation and oscillatory for high activation, the coherent organization of subnetworks to generate macroscopic function is very complex and for the time being, may be best described by the theory of coordination dynamics. Since oscillatory firing has also been observed by us in single motor unit firing patterns measured electromyographically, it seems possible to follow up therapeutic intervention in patients with spinal cord and brain lesions not only based on the activity levels and phases of motor programs during locomotion but also based on the physiologic and pathophysiologic firing patterns and recruitment of spinal oscillators. The improvement of the coordination dynamics of the CNS can be partly measured directly by rhythmicity upon the patient performing rhythmic movements coordinated up to milliseconds. Since rhythmic dynamic, coordinated, stereotyped movements are mainly located in the spinal cord and only little supraspinal drive is necessary to initiate, maintain, and terminate them, rhythmic, dynamic, coordinated movements were used in therapy to enforce reorganization of the lesioned CNS by improving the self-organization and relative coordination of spinal oscillators (and their interactions with occasionally firing motoneurons) which became pathologic in their firing following CNS lesion. Paraparetic, tetraparetic spinal cord and brain-lesioned patients re-learned running and other movements by an oscillator formation and coordination dynamic therapy. Our development in neurorehabilitation is in accordance with those of theoretical and computational neurosciences which deal with the self-organization of neuronal networks. In particular, jumping on a springboard 'in-phase' and in 'anti-phase' to re-learn phase relations of oscillator coupling can be understood in the framework of the Haken-Kelso-Bunz coordination dynamic model. By introducing broken symmetry, intention, learning and spasticity in the landscape of the potential function of the integrated CNS activity, the change in self-organization becomes understandable. Movement patterns re-learned by oscillator formation and coordination dynamic therapy evolve from reorganization and regeneration of the lesioned CNS by cooperative and competitive interplay between intrinsic coordination dynamics, extrinsic therapy related inputs with physiologic re-afferent input, including intention, motivation, supervised learning, interpersonal coordination, and genetic constraints including neurogenesis. (ABSTRACT TRUNCATED)

Fatal persistent pulmonary hypertension presenting late in the neonatal period.

PubMed Central

Raine, J; Hislop, A A; Redington, A N; Haworth, S G; Shinebourne, E A

1991-01-01

Two cases of fatal idiopathic persistent pulmonary hypertension presented late in the neonatal period. Lungs were examined histologically by light and electron microscopy, and immunocytochemical studies were used to identify nerves. There was extension of medial smooth muscle distally along the arterial pathway so that most precapillary arteries had completely muscular walls, which in some cases completely obliterated the vessel lumen. Enlarged endothelial cells also contributed to the reduction in the size of the lumen. Nerve fibres accompanying muscular arteries were found in the alveolar region, more distal than is normal. The predominant neuropeptide was the vasoconstrictor tyrosine. Possible aetiological factors in persistent pulmonary hypertension of the newborn are increased muscularity of the peripheral pulmonary arteries antenatally, an increase in the number of vasoconstrictor nerves, or an imbalance in the production of leukotrienes and prostacyclins in the perinatal period. Images Figure 1 Figure 2 Figure 3 PMID:2025031

[Polyneuropathy in diabetes type 1].

PubMed

Wilczyńska, Małgorzata

2002-01-01

Diabetic neuropathy is a clinical state of nerve damage caused by hyperglicaemia, raised activation of polyol pathway, oxydative stress, changes in endoneurial arteries and myelinated fibres. Patient complains of pain and paresthesiae in hands and limbs. The feelings of pain, temperature, touch, vibration are significantly reduced. The changes may also concern cranial nerves (IIII, IV, VI, VII), intracostal nerves, hands and limbs (Garland and Tavemer syndrome). Autonomic neuropathy concerns the impairment of autonomic functions of cardio-vascular, gastro-intestinal, uro-genital and other systems. The treatment concerns the improvement of diabetes metabolic control. Antiinflammatory antisteroid drugs are widely used but their usefulness is limited. Antidepressive drugs are the most often used group. The improvement is observed after 6 months of treatment. The side effects - orthostatic hypotension, heart rhythm disturbation and obstipation are harmful for the patients with coronary heart disease. In the cases of persistent pain the oral antiepileptic drugs may be used or cream with capsaicin for skin surface.

Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation.

PubMed

Chavolla-Calderón, Mara; Bayer, Meggan K; Fontán, J Julio Pérez

2003-04-01

Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex-mediated and stretch-mediated injuries. Reconstitution of PPT-A gene-deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene-deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract.

Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation

PubMed Central

Chavolla-Calderón, Mara; Bayer, Meggan K.; Fontán, J. Julio Pérez

2003-01-01

Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex–mediated and stretch-mediated injuries. Reconstitution of PPT-A gene–deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene–deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract. PMID:12671046

The effect of the mammalian neuropeptide, gastrin-releasing peptide (GRP), on gastrointestinal and pancreatic hormone secretion in man.

PubMed

Wood, S M; Jung, R T; Webster, J D; Ghatei, M A; Adrian, T E; Yanaihara, N; Yanaihara, C; Bloom, S R

1983-10-01

Gastrin-releasing peptide, a newly isolated mammalian peptide similar in its structure and actions to the amphibian peptide, bombesin, has recently been localized to nerves in the brain, gut and pancreas. The present study investigates its effects on gut and pancreatic peptides in man. Intravenous infusion of 0.7 and 2.9 pmol min-1 kg-1 produced significant elevation of plasma gastrin, cholecystokinin-like immunoreactivity and neurotensin. It was found also to potentiate glucose-dependent insulin secretion. Its specific location in nerve fibres in the proximal gut and pancreas and its selective effect on gastroenteropancreatic peptides may favour its role as a physiological regulatory neuropeptide.

A nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle.

PubMed

van Bolhuis, A I; Holsheimer, J; Savelberg, H H

2001-05-30

Electrical stimulation of peripheral nerve results in a motor-unit recruitment order opposite to that attained by natural neural control, i.e. from large, fast-fatiguing to progressively smaller, fatigue-resistant motor-units. Yet animal studies involving physiological exercise protocols of low intensity and long duration require minimal fatigue. The present study sought to apply a nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle. Two pulse generators were used, independently supplying short supramaximal cathodal stimulating pulses (0.5 ms) and long subthreshold cathodal inactivating pulses (1.5 s) to the sciatic nerve. Propagation of action potentials was selectively blocked in nerve fibres of different diameter by adjusting the strength of the inactivating current. A tensile-testing machine was used to gauge isometric muscle force of the plantaris and both heads of the gastrocnemius muscle. The order of motor-unit recruitment was estimated from twitch characteristics, i.e. peak force and relaxation time. The results showed prolonged relaxation at lower twitch peak forces as the intensity of the inactivating current increased, indicating a reduction of the number of large motor-units to force production. It is shown that the nerve stimulation method described is effective in mimicking physiological muscle control.

Spontaneous action potentials and neural coding in unmyelinated axons.

PubMed

O'Donnell, Cian; van Rossum, Mark C W

2015-04-01

The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.

The impact of fibre orientation on T1-relaxation and apparent tissue water content in white matter.

PubMed

Schyboll, Felix; Jaekel, Uwe; Weber, Bernd; Neeb, Heiko

2018-02-20

Recent MRI studies have shown that the orientation of nerve fibres relative to the main magnetic field affects the R 2 *(= 1/T 2 *) relaxation rate in white matter (WM) structures. The underlying physical causes have been discussed in several studies but are still not completely understood. However, understanding these effects in detail is of great importance since this might serve as a basis for the development of new diagnostic tools and/or improve quantitative susceptibility mapping techniques. Therefore, in addition to the known angular dependence of R 2 *, the current study investigates the relationship between fibre orientation and the longitudinal relaxation rate, R 1 (= 1/T 1 ), as well as the apparent water content. For a group of 16 healthy subjects, a series of gradient echo, echo-planar and diffusion weighted images were acquired at 3T from which the decay rates, the apparent water content and the diffusion direction were reconstructed. The diffusion weighted data were used to determine the angle between the principle fibre direction and the main magnetic field to examine the angular dependence of R 1 and apparent water content. The obtained results demonstrate that both parameters depend on the fibre orientation and exhibit a positive correlation with the angle between fibre direction and main magnetic field. These observations could be helpful to improve and/or constrain existing biophysical models of brain microstructure by imposing additional constraints resulting from the observed angular dependence R 1 and apparent water content in white matter.

Mutations in COA7 cause spinocerebellar ataxia with axonal neuropathy.

PubMed

Higuchi, Yujiro; Okunushi, Ryuta; Hara, Taichi; Hashiguchi, Akihiro; Yuan, Junhui; Yoshimura, Akiko; Murayama, Kei; Ohtake, Akira; Ando, Masahiro; Hiramatsu, Yu; Ishihara, Satoshi; Tanabe, Hajime; Okamoto, Yuji; Matsuura, Eiji; Ueda, Takehiro; Toda, Tatsushi; Yamashita, Sumimasa; Yamada, Kenichiro; Koide, Takashi; Yaguchi, Hiroaki; Mitsui, Jun; Ishiura, Hiroyuki; Yoshimura, Jun; Doi, Koichiro; Morishita, Shinichi; Sato, Ken; Nakagawa, Masanori; Yamaguchi, Masamitsu; Tsuji, Shoji; Takashima, Hiroshi

2018-06-01

Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT. We also found that all four patients had characteristic neurological features of peripheral neuropathy and ataxia with cerebellar atrophy, and some patients showed leukoencephalopathy or spinal cord atrophy on MRI scans. Validated mutations were located at highly conserved residues among different species and segregated with the disease in each family. Nerve conduction studies showed axonal sensorimotor neuropathy. Sural nerve biopsies showed chronic axonal degeneration with a marked loss of large and medium myelinated fibres. An immunohistochemical assay with an anti-COA7 antibody in the sural nerve from the control patient showed the positive expression of COA7 in the cytoplasm of Schwann cells. We also observed mildly elevated serum creatine kinase levels in all patients and the presence of a few ragged-red fibres and some cytochrome c oxidase-negative fibres in a muscle biopsy obtained from one patient, which was suggestive of subclinical mitochondrial myopathy. Mitochondrial respiratory chain enzyme assay in skin fibroblasts from the three patients showed a definitive decrease in complex I or complex IV. Immunocytochemical analysis of subcellular localization in HeLa cells indicated that mutant COA7 proteins as well as wild-type COA7 were localized in mitochondria, which suggests that mutant COA7 does not affect the mitochondrial recruitment and may affect the stability or localization of COA7 interaction partners in the mitochondria. In addition, Drosophila COA7 (dCOA7) knockdown models showed rough eye phenotype, reduced lifespan, impaired locomotive ability and shortened synaptic branches of motor neurons. Our results suggest that loss-of-function COA7 mutation is responsible for the phenotype of the presented patients, and this new entity of disease would be referred to as spinocerebellar ataxia with axonal neuropathy type 3.

Autonomic innervation of immune organs and neuroimmune modulation.

PubMed

Mignini, F; Streccioni, V; Amenta, F

2003-02-01

1. Increasing evidence indicates the occurrence of functional interconnections between immune and nervous systems, although data available on the mechanisms of this bi-directional cross-talking are frequently incomplete and not always focussed on their relevance for neuroimmune modulation. 2. Primary (bone marrow and thymus) and secondary (spleen and lymph nodes) lymphoid organs are supplied with an autonomic (mainly sympathetic) efferent innervation and with an afferent sensory innervation. Anatomical studies have revealed origin, pattern of distribution and targets of nerve fibre populations supplying lymphoid organs. 3. Classic (catecholamines and acetylcholine) and peptide transmitters of neural and non-neural origin are released in the lymphoid microenvironment and contribute to neuroimmune modulation. Neuropeptide Y, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide represent the neuropeptides most involved in neuroimmune modulation. 4. Immune cells and immune organs express specific receptors for (neuro)transmitters. These receptors have been shown to respond in vivo and/or in vitro to the neural substances and their manipulation can alter immune responses. Changes in immune function can also influence the distribution of nerves and the expression of neural receptors in lymphoid organs. 5. Data on different populations of nerve fibres supplying immune organs and their role in providing a link between nervous and immune systems are reviewed. Anatomical connections between nervous and immune systems represent the structural support of the complex network of immune responses. A detailed knowledge of interactions between nervous and immune systems may represent an important basis for the development of strategies for treating pathologies in which altered neuroimmune cross-talking may be involved.

Immunomodulation of afferent neurons in guinea-pig isolated airway.

PubMed

Riccio, M M; Myers, A C; Undem, B J

1996-03-01

1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P < 0.005). Mechanical sensitivities of afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) from non-immunized control guinea-pig airways were unaffected by antigen (n = 13). 4. Antigen did not overtly cause action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in excitability persisted beyond the duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent nerve terminals projecting from the airway and thus may contribute to the pathophysiology of allergic airway diseases.

Gamma loop contributing to maximal voluntary contractions in man.

PubMed Central

Hagbarth, K E; Kunesch, E J; Nordin, M; Schmidt, R; Wallin, E U

1986-01-01

A local anaesthetic drug was injected around the peroneal nerve in healthy subjects in order to investigate whether the resulting loss in foot dorsiflexion power in part depended on a gamma-fibre block preventing 'internal' activation of spindle end-organs and thereby depriving the alpha-motoneurones of an excitatory spindle inflow during contraction. The motor outcome of maximal dorsiflexion efforts was assessed by measuring firing rates of individual motor units in the anterior tibial (t.a.) muscle, mean voltage e.m.g. from the pretibial muscles, dorsiflexion force and range of voluntary foot dorsiflexion movements. The tests were performed with and without peripheral conditioning stimuli, such as agonist or antagonist muscle vibration or imposed stretch of the contracting muscles. As compared to control values of t.a. motor unit firing rates in maximal isometric voluntary contractions, the firing rates were lower and more irregular during maximal dorsiflexion efforts performed during subtotal peroneal nerve blocks. During the development of paresis a gradual reduction of motor unit firing rates was observed before the units ceased responding to the voluntary commands. This change in motor unit behaviour was accompanied by a reduction of the mean voltage e.m.g. activity in the pretibial muscles. At a given stage of anaesthesia the e.m.g. responses to maximal voluntary efforts were more affected than the responses evoked by electric nerve stimuli delivered proximal to the block, indicating that impaired impulse transmission in alpha motor fibres was not the sole cause of the paresis. The inability to generate high and regular motor unit firing rates during peroneal nerve blocks was accentuated by vibration applied over the antagonistic calf muscles. By contrast, in eight out of ten experiments agonist stretch or vibration caused an enhancement of motor unit firing during the maximal force tasks. The reverse effects of agonist and antagonist vibration on the ability to activate the paretic muscles were evidenced also by alterations induced in mean voltage e.m.g. activity, dorsiflexion force and range of dorsiflexion movements. The autogenetic excitatory and the reciprocal inhibitory effects of muscle vibration rose in strength as the vibration frequency was raised from 90 to 165 Hz. Reflex effects on maximal voluntary contraction strength similar to those observed during partial nerve blocks were not seen under normal conditions when the nerve supply was intact.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3612576

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

PubMed

Dusch, M; van der Ham, J; Weinkauf, B; Benrath, J; Rukwied, R; Ringkamp, M; Schmelz, M; Treede, R-D; Baumgärtner, U

2016-05-01

Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 μV vs. 24.6 ± 1.7 μV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors. © 2015 European Pain Federation - EFIC®

Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy

PubMed Central

Nicotra, Alessia; Newman, Claus; Johnson, Martin; Eremin, Oleg; Friede, Tim; Malik, Omar; Nicholas, Richard

2016-01-01

Background Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life. Methods Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment. Results Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)). Conclusions We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation. PMID:27100829

NO nerves in a tapeworm. NADPH-diaphorase histochemistry in adult Hymenolepis diminuta.

PubMed

Gustafsson, M K; Lindholm, A M; Terenina, N B; Reuter, M

1996-12-01

The free radical nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS), has recently been discovered to function as a neuronal messenger. The presence of NOS was detected in the nervous system of adult Hymenolepis diminuta with NADPH-diaphorase (NADPH-d) histochemistry. The NADPH-d histochemical reaction is regarded as a selective marker for NOS in neuronal tissue. NADPH-d staining was observed in nerve fibres in the main and minor nerve cords and the transverse ring commissures, and in cell bodies in the brain commissure, along the main nerve cords, in the suckers and the rostellar sac. NADPH-d staining was also observed in the wall of the internal seminal vesicle and the genital atrium. The pattern of NADPH-d staining was compared with that of the 5-HT immunoreactive nervous elements. The NADPH-d staining reaction and the 5-HT immunoreactivity occur in separate sets of neurons. This is the first time the NADPH-d reaction has been demonstrated in the nervous system of a flatworm, indicating that NOS is present and that NO can be produced at this level of evolution.

Distribution of enkephalin-like immunoreactivity in the cat digestive tract.

PubMed

Bagnol, D; Henry, M; Cupo, A; Julé, Y

1997-05-12

Immunohistochemical investigations were carried out to determine the pattern of distribution of methionine- and leucine-enkephalin-like materials in the cat pylorus, duodenum, ileum and proximal and distal colon. The present results indicate that leucine-enkephalin-like materials are less densely distributed than methionine-enkephalin-like materials, but that the two patterns of distribution show some similarities. Considerable regional differences exist however in the distribution of these enkephalin-like materials in the muscular layers. In the duodenum, ileum and proximal colon, the immunoreactivity was mainly confined to the myenteric plexus and the circular muscle layer, where it was present in nerve cell bodies and in numerous fibres. In the longitudinal muscle and submucous layers, a few immunoreactive fibres were observed which sometimes surrounded blood vessels. In the pylorus and the distal colon, however, numerous immunoreactive fibres were observed in the longitudinal and circular muscle layers; the immunoreactivity was detected in the cell bodies of numerous myenteric plexus neurons but those of only a few submucous plexus neurons. In addition, the pylorus tissues contained immunoreactive plexi which were localized either within the longitudinal muscle or between the serosa and the longitudinal muscle layer. These plexi were connected to the myenteric plexus by immunoreactive nerve strands. In all the small intestinal segments studied, numerous immunoreactive varicosities were present in the deep muscular plexus, in the inner part of the circular muscle layer. Our results suggest that in cats, the nervous control of external muscular layers mediated by enkephalins shows regional differences. In the pylorus and the distal colon, it involves both the longitudinal and circular muscle layers, whereas in other intestinal segments, only the circular muscle layer is involved.

Evolutionary origins of taste buds: phylogenetic analysis of purinergic neurotransmission in epithelial chemosensors

PubMed Central

Kirino, Masato; Parnes, Jason; Hansen, Anne; Kiyohara, Sadao; Finger, Thomas E.

2013-01-01

Taste buds are gustatory endorgans which use an uncommon purinergic signalling system to transmit information to afferent gustatory nerve fibres. In mammals, ATP is a crucial neurotransmitter released by the taste cells to activate the afferent nerve fibres. Taste buds in mammals display a characteristic, highly specific ecto-ATPase (NTPDase2) activity, suggesting a role in inactivation of the neurotransmitter. The purpose of this study was to test whether the presence of markers of purinergic signalling characterize taste buds in anamniote vertebrates and to test whether similar purinergic systems are employed by other exteroceptive chemosensory systems. The species examined include several teleosts, elasmobranchs, lampreys and hagfish, the last of which lacks vertebrate-type taste buds. For comparison, Schreiner organs of hagfish and solitary chemosensory cells (SCCs) of teleosts, both of which are epidermal chemosensory end organs, were also examined because they might be evolutionarily related to taste buds. Ecto-ATPase activity was evident in elongate cells in all fish taste buds, including teleosts, elasmobranchs and lampreys. Neither SCCs nor Schreiner organs show specific ecto-ATPase activity, suggesting that purinergic signalling is not crucial in those systems as it is for taste buds. These findings suggest that the taste system did not originate from SCCs but arose independently in early vertebrates. PMID:23466675

Evolutionary origins of taste buds: phylogenetic analysis of purinergic neurotransmission in epithelial chemosensors.

PubMed

Kirino, Masato; Parnes, Jason; Hansen, Anne; Kiyohara, Sadao; Finger, Thomas E

2013-03-06

Taste buds are gustatory endorgans which use an uncommon purinergic signalling system to transmit information to afferent gustatory nerve fibres. In mammals, ATP is a crucial neurotransmitter released by the taste cells to activate the afferent nerve fibres. Taste buds in mammals display a characteristic, highly specific ecto-ATPase (NTPDase2) activity, suggesting a role in inactivation of the neurotransmitter. The purpose of this study was to test whether the presence of markers of purinergic signalling characterize taste buds in anamniote vertebrates and to test whether similar purinergic systems are employed by other exteroceptive chemosensory systems. The species examined include several teleosts, elasmobranchs, lampreys and hagfish, the last of which lacks vertebrate-type taste buds. For comparison, Schreiner organs of hagfish and solitary chemosensory cells (SCCs) of teleosts, both of which are epidermal chemosensory end organs, were also examined because they might be evolutionarily related to taste buds. Ecto-ATPase activity was evident in elongate cells in all fish taste buds, including teleosts, elasmobranchs and lampreys. Neither SCCs nor Schreiner organs show specific ecto-ATPase activity, suggesting that purinergic signalling is not crucial in those systems as it is for taste buds. These findings suggest that the taste system did not originate from SCCs but arose independently in early vertebrates.

Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage

PubMed Central

Hood, D C; Harizman, N; Kanadani, F N; Grippo, T M; Baharestani, S; Greenstein, V C; Liebmann, J M; Ritch, R

2007-01-01

Aim To assess the accuracy of optical coherence tomography (OCT) in detecting damage to a hemifield, patients with hemifield defects confirmed on both static automated perimetry (SAP) and multifocal visual evoked potentials (mfVEP) were studied. Methods Eyes of 40 patients with concomitant SAP and mfVEP glaucomatous loss and 25 controls underwent OCT retinal nerve fibre layer (RNFL), mfVEP and 24‐2 SAP tests. For the mfVEP and 24‐2 SAP, a hemifield was defined as abnormal based upon cluster criteria. On OCT, a hemifield was considered abnormal if one of the five clock hour sectors (3 and 9 o'clock excluded) was at <1% (red) or two were at <5% (yellow). Results Seventy seven (43%) of the hemifields were abnormal on both mfVEP and SAP tests. The OCT was abnormal for 73 (95%) of these. Only 1 (1%) of the 100 hemifields of the controls was abnormal on OCT. Sensitivity/specificity (one eye per person) was 95/98%. Conclusions The OCT RNFL test accurately detects abnormal hemifields confirmed on both subjective and objective functional tests. Identifying abnormal hemifields with a criterion of 1 red (1%) or 2 yellow (5%) clock hours may prove useful in clinical practice. PMID:17301118

The epistellar body and what followed from its discovery.

PubMed

Young, J Z

1990-07-01

The sequence of discoveries that has followed the investigation of this small yellow spot shows the value of studies begun out of "mere curiosity". The spot occurs on the stellate ganglion of octopods. It proved to be an enclosed sac, perhaps a gland. The search for it in squids and cuttlefishes led to the discovery of the giant nerve fibres. At first they were thought to be veins but we soon showed that they were nerve fibres concerned with jet propulsion. Their action potentials, membranes and synapses have been used for thousand of studies, including those that led to the Hodkin Huxley equations. They have been the basis of much of modern neuroscience. The epistellar body itself proved not to be a gland but a photoreceptor. Comparable photosensitive vesicles are especially large in the heads of deep-sea squids. In the mesopelagic ones they allow the squid to conceal itself by counterillumination, matching its own light output to the light coming from above. In bathypelagic squids the vesicles are enormous and probably keep the animals in the dark, where they breed. The function of the epistellar body, lying within the mantle of octopods is still unknown. It may act in the transparent larval stage to trigger the ejection of luminous plankton, which would be a hazard.

Cold-evoked potentials - Ready for clinical use?

PubMed

Hüllemann, P; Nerdal, A; Binder, A; Helfert, S; Reimer, M; Baron, R

2016-11-01

Cold-evoked potentials (CEPs) are known to assess the integrity of A-delta fibres and the spinothalamic tract. Nevertheless, the clinical value was not investigated previously. The aim of this study was to measure CEPs in 16 healthy subjects from the face, hand and foot sole and to investigate whether CEPs reliably detect A-delta fibre abnormalities. Swift cold stimuli were applied to the skin with a commercially available thermode, which cooled down from 30 to 25 °C in approximately 0.5 s. CEP latencies (N1, N2 and P2) and amplitudes (N1, N2/P2) were recorded with EEG. Reversible A-fibre function loss was induced by applying a selective A-fibre block at the superficial radial nerve. In all 16 subjects CEPs could be recorded from all locations; N2, P2 mean latencies were 276.4 ± 38.9 and 389.8 ± 52.5 (face), 318.6 ± 31.6 ms and 477.7 ± 43.6 (hand), and 627.6 ± 84.4 and 774.2 ± 94.0 (foot sole). N2/P2 amplitudes were 10.7 ± 4.1, 11.3 ± 4.1 and 7.5 ± 4.1 μV. During A-fibre block no CEPs were detectable in the grand average, which restored 10 min after block removal. CEPs were reliably recorded in healthy subjects at the hand, face and foot. Experimentally induced reversible A-delta fibre function loss was detected by CEPs. Functional recovery was assessed as well. This study is basis for further CEP evaluation studies and might be the first step for implementing CEPs in clinical routine for the early diagnosis of small-fibre disease. WHAT DOES THIS STUDY ADD?: Cold-evoked potentials are capable of reliably measuring A-delta fibre integrity, loss of function and functional recovery in healthy subjects, which is an essential prerequisite for diagnostic use in patients with small-fibre disease. © 2016 European Pain Federation - EFIC®.

Contribution of capsaicin-sensitive primary afferents to mechanical hyperalgesia induced by ventral root transection in rats: the possible role of BDNF.

PubMed

Li, Wei; Wang, Jian-Xiu; Zhou, Zhong-He; Lu, Yao; Li, Xiao-Qiu; Liu, Bao-Jun; Chen, Hui-Sheng

2016-01-01

A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed. The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT. The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin. Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

Pharmacological studies upon neurones of the lateral geniculate nucleus of the cat

PubMed Central

Curtis, D. R.; Davis, R.

1962-01-01

Indoles related to 5-hydroxytryptamine, lysergic acid derivatives, phenethylamine derivatives and some other compounds have been applied electrophoretically to the neurones of the lateral geniculate nucleus of the cat anaesthetized with pentobarbitone sodium. Many of these compounds, particularly 4-, 5- and 7-hydroxytryptamine and ergometrine, depress the orthodromic excitation of the neurones by volleys in optic nerve fibres, but do not affect antidromic excitation by volleys in the optic radiation or chemical excitation by L-glutamic acid. It is concluded that the active depressants either block the access of the excitatory transmitter to subsynaptic receptors or prevent the release of the transmitter from optic nerve terminals. The structure-activity relationships of the depressant substances are discussed. PMID:13882768

The effects of saxitoxin and tetrodotoxin on nerve conduction in the presence of lithium ions and of magnesium ions

PubMed Central

Evans, M. H.

1969-01-01

1. It has been shown that nerve fibres from rat cauda equina will conduct action potentials after immersion in saline in which lithium chloride is substituted for sodium chloride. 2. Both saxitoxin and tetrodotoxin inhibit lithium-generated action potentials. The concentration of toxin needed to inhibit the lithium-generated action potentials is similar to that needed to inhibit sodium-generated action potentials. 3. If magnesium chloride is added to the saline to give a concentration of 10-15 mM there is usually a slight fall in amplitude of the compound action potential. Saxitoxin and tetrodotoxin now inhibit the action potential to a greater degree than in the absence of magnesium ions. PMID:5789802

Contribution of impaired myofibril and ryanodine receptor function to prolonged low-frequency force depression after in situ stimulation in rat skeletal muscle.

PubMed

Watanabe, Daiki; Kanzaki, Keita; Kuratani, Mai; Matsunaga, Satoshi; Yanaka, Noriyuki; Wada, Masanobu

2015-06-01

The aim of this study was to examine whether prolonged low-frequency force depression (PLFFD) that occurs in situ is the result of decreased myofibrillar Ca(2+) sensitivity and/or reduced sarcoplasmic reticulum (SR) Ca(2+) release. Intact rat gastrocnemius muscles were electrically stimulated via the sciatic nerve until force was reduced to ~50% of the initial and dissected 30 min following the cessation of stimulation. Skinned fibre and whole muscle analyses were performed in the superficial region composed exclusively of type IIB fibres. Fatiguing stimulation significantly reduced the ratio of force at low frequency to that at high frequency to 65% in skinned fibres (1 vs. 50 Hz) and 73% in whole muscles (20 vs. 100 Hz). In order to evaluate changes in myofibrillar Ca(2+) sensitivity and ryanodine receptor caffeine sensitivity, skinned fibres were activated in Ca(2+)- and caffeine-containing solutions, respectively. Skinned fibres from fatigued muscles displayed decreased caffeine sensitivity together with increased myofibrillar Ca(2+) sensitivity. Treatment with 2,2'-dithiodipyridine and reduced glutathione induced a smaller increase in myofibrillar Ca(2+)sensitivity in fatigued than in rested fibres. In fatigued muscles, S-glutathionylation of troponin I was increased and submaximal SR Ca(2+) release, induced by 4-chloro-m-cresol, was decreased. These findings suggest that in the early stage of PLFFD that occurs in fast-twitch muscles of exercising animals and humans, S-glutathionylation of troponin I may attenuate PLFFD by increasing myofibrillar Ca(2+) sensitivity and that under such a circumstance, PLFFD may be ascribable to failure of SR Ca(2+) release.

Intraspinal microstimulation preferentially recruits fatigue-resistant muscle fibres and generates gradual force in rat

PubMed Central

Bamford, JA; Putman, CT; Mushahwar, VK

2005-01-01

Intraspinal microstimulation (ISMS), a novel rehabilitative therapy consisting of stimulation through fine, hair-like microwires targeted at the ventral spinal cord, has been proposed for restoring standing and walking following spinal cord injury. This study compared muscle recruitment characteristics of ISMS with those produced by peripheral nerve cuff stimulation (NCS). Thirty-three minutes of either ISMS or NCS at 1, 20 or 50 s−1 and 1.2 × threshold (T) amplitude depleted glycogen from muscle fibres of vastus lateralis and rectus femoris. ISMS and NCS were also carried out at 20 s−1 and 3.0T. Muscle serial sections were stained for glycogen and for myosin heavy chain (MHC)-based fibre types using a panel of monoclonal antibodies. The results of this study show that ISMS recruited fatigue-resistant (FR) fibres at 2.9, 1.9, 1.7 and 2.5 times their relative MHC content at 1, 20 and 50 s−1 1.2T and 20 s−1 3.0T, respectively. In contrast, NCS recruited FR fibres at 1.2, 1.0, 2.1 and 0.0 times their MHC content at 1, 20 and 50 s−1 1.2T and 20 s−1 3.0T, respectively. The proportion of FR fibres recruited by ISMS and NCS was significantly different in the 20 s−1 3.0T condition (P < 0.0001). We also report that force recruitment curves were 4.9-fold less steep (P < 0.019) for ISMS than NCS. The findings of this study provide evidence for the efficacy of ISMS and further our understanding of muscle recruitment properties of this novel rehabilitative therapy. PMID:16239281

Facial arthralgia and myalgia: can they be differentiated by trigeminal sensory assessment?

PubMed

Eliav, Eli; Teich, Sorin; Nitzan, Dorit; El Raziq, Daood Abid; Nahlieli, Oded; Tal, Michael; Gracely, Richard H; Benoliel, Rafael

2003-08-01

Heat and electrical detection thresholds were assessed in 72 patients suffering from painful temporomandibular disorder. Employing widely accepted criteria, 44 patients were classified as suffering from temporomandibular joint (TMJ) arthralgia (i.e. pain originating from the TMJ) and 28 from myalgia (i.e. pain originating from the muscles of mastication). Electrical stimulation was employed to assess thresholds in large myelinated nerve fibers (Abeta) and heat application to assess thresholds in unmyelinated nerve fibers (C). The sensory tests were performed bilaterally in three trigeminal nerve sites: the auriculotemporal nerve territory (AUT), buccal nerve territory (BUC) and the mental nerve territory (MNT). In addition, 22 healthy asymptomatic controls were examined. A subset of ten arthralgia patients underwent arthrocentesis and electrical detection thresholds were additionally assessed following the procedure. Electrical detection threshold ratios were calculated by dividing the affected side by the control side, thus reduced ratios indicate hypersensitivity of the affected side. In control patients, ratios obtained at all sites did not vary significantly from the expected value of 'one' (mean with 95% confidence intervals; AUT, 1:0.95-1.06; BUC, 1.01:0.93-1.11; MNT, 0.97:0.88-1.05, all areas one sample analysis P>0.05). In arthralgia patients mean ratios (+/-SEM) obtained for the AUT territory (0.63+/-0.03) were significantly lower compared to ratios for the MNT (1.02+/-0.03) and BUC (0.96+/-0.04) territories (repeated measures analysis of variance (RANOVA), P<0.0001) and compared to the AUT ratios in myalgia (1.27+/-0.09) and control subjects (1+/-0.06, ANOVA, P<0.0001). In the myalgia group the electrical detection threshold ratios in the AUT territory were significantly elevated compared to the AUT ratios in control subjects (Dunnett test, P<0.05), but only approached statistical significance compared to the MNT (1.07+/-0.04) and BUC (1.11+/-0.06) territories (RANOVA, F(2,27)=3.12, P=0.052). There were no significant differences between and within the groups for electrical detection threshold ratios in the BUC and MNT nerve territories, and for the heat detection thresholds in all tested sites. Following arthrocentesis, mean electrical detection threshold ratios in the AUT territory were significantly elevated from 0.64+/-0.06 to 0.99+/-0.04 indicating resolution of the hypersensitivity (paired t-test, P=0.001). In conclusion, large myelinated fiber hypersensitivity is found in the skin overlying TMJs with clinical pain and pathology but is not found in controls. In patients with muscle-related facial pain there was significant elevation of the electrical detection threshold in the AUT region.

Thermoreception and nociception of the skin: a classic paper of Bessou and Perl and analyses of thermal sensitivity during a student laboratory exercise.

PubMed

Kuhtz-Buschbeck, Johann P; Andresen, Wiebke; Göbel, Stephan; Gilster, René; Stick, Carsten

2010-06-01

About four decades ago, Perl and collaborators were the first ones who unambiguously identified specifically nociceptive neurons in the periphery. In their classic work, they recorded action potentials from single C-fibers of a cutaneous nerve in cats while applying carefully graded stimuli to the skin (Bessou P, Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025-1043, 1969). They discovered polymodal nociceptors, which responded to mechanical, thermal, and chemical stimuli in the noxious range, and differentiated them from low-threshold thermoreceptors. Their classic findings form the basis of the present method that undergraduate medical students experience during laboratory exercises of sensory physiology, namely, quantitative testing of the thermal detection and pain thresholds. This diagnostic method examines the function of thin afferent nerve fibers. We collected data from nearly 300 students that showed that 1) women are more sensitive to thermal detection and thermal pain at the thenar than men, 2) habituation shifts thermal pain thresholds during repetititve testing, 3) the cold pain threshold is rather variable and lower when tested after heat pain than in the reverse case (order effect), and 4) ratings of pain intensity on a visual analog scale are correlated with the threshold temperature for heat pain but not for cold pain. Median group results could be reproduced in a retest. Quantitative sensory testing of thermal thresholds is feasible and instructive in the setting of a laboratory exercise and is appreciated by the students as a relevant and interesting technique.

Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients.

PubMed

Singleton, J Robinson; Marcus, Robin L; Lessard, Margaret K; Jackson, Justin E; Smith, A Gordon

2015-01-01

Unmyelinated cutaneous axons are vulnerable to physical and metabolic injury, but also capable of rapid regeneration. This balance may help determine risk for peripheral neuropathy associated with diabetes or metabolic syndrome. Capsaicin application for 48 hours induces cutaneous fibers to die back into the dermis. Regrowth can be monitored by serial skin biopsies to determine intraepidermal nerve fiber density (IENFD). We used this capsaicin axotomy technique to examine the effects of exercise on cutaneous regenerative capacity in the setting of metabolic syndrome. Baseline ankle IENFD and 30-day cutaneous regeneration after thigh capsaicin axotomy were compared for participants with type 2 diabetes (n = 35) or metabolic syndrome (n = 32) without symptoms or examination evidence of neuropathy. Thirty-six participants (17 with metabolic syndrome) then joined twice weekly observed exercise and lifestyle counseling. Axotomy regeneration was repeated in month 4 during this intervention. Baseline distal leg IENFD was significantly reduced for both metabolic syndrome and diabetic groups. With exercise, participants significantly improved exercise capacity and lower extremity power. Following exercise, 30-day reinnervation rate improved (0.051 ± 0.027 fibers/mm/day before vs 0.072 ± 0.030 after exercise, p = 0.002). Those who achieved improvement in more metabolic syndrome features experienced a greater degree of 30-day reinnervation (p < 0.012). Metabolic syndrome was associated with reduced baseline IENFD and cutaneous regeneration capacity comparable to that seen in diabetes. Exercise-induced improvement in metabolic syndrome features increased cutaneous regenerative capacity. The results underscore the potential benefit to peripheral nerve function of a behavioral modification approach to metabolic improvement. © 2014 American Neurological Association.

Differentiating therapy-induced leukoencephalopathy from unmyelinated white matter in children treated for acute lymphoblastic leukemia (ALL)

NASA Astrophysics Data System (ADS)

Reddick, Wilburn E.; Glass, John O.; Pui, Ching-Hon

2003-05-01

Reliably detecting subtle therapy-induced leukoencephalopathy in children treated for cancer is a challenging task due to its nearly identical MR properties and location with unmyelinated white matter. T1, T2, PD, and FLAIR images were collected for 44 children aged 1.7-18.7 (median 5.9) years near the start of therapy for ALL. The ICBM atlas and corresponding apriori maps were spatially normalized to each patient and resliced using SPM99 software. A combined imaging set consisting of MR images and WM, GM and CSF apriori maps were then analyzed with a Kohonen Self-Organizing Map. Vectors from hyperintense regions were compared to normal appearing genu vectors from the same patient. Analysis of the distributions of the differences, calculated on T2 and FLAIR images, revealed two distinct groups. The first large group, assumed normal unmyelinated white matter, consisted of 37 patients with changes in FLAIR ranging from 80 to 147 (mean 117-/+17) and T2 ranging from 92 to 217 (mean 144-/+28). The second group, assumed leukoencephalopathy, consisted of seven patients with changes in FLAIR ranging from 154 to 196 (mean 171-/+19) and T2 ranging from 190 to 287 (mean 216-/+33). A threshold was established for both FLAIR (change > 150) and T2 (change > 180).

Bilirubin and its oxidation products damage brain white matter

PubMed Central

Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

2014-01-01

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

Desmin and nerve terminal expression during embryonic development of the lateral pterygoid muscle in mice.

PubMed

Yamamoto, Masahito; Shinomiya, Takashi; Kishi, Asuka; Yamane, Shigeki; Umezawa, Takashi; Ide, Yoshinobu; Abe, Shinichi

2014-09-01

In adults, the lateral pterygoid muscle (LPM) is usually divided into the upper and lower head, between which the buccal nerve passes. Recent investigations have demonstrated foetal developmental changes in the topographical relationship between the human LPM and buccal nerve. However, as few studies have investigated this issue, we clarified the expression of desmin and nerve terminal distribution during embryonic development of the LPM in mice. We utilized immunohistochemical staining and reverse transcription chain reaction (RT-PCR) to clarify the expression of desmin and nerve terminal distribution. We observed weak expression of desmin in the LPM at embryonic day (ED) 11, followed by an increase in expression from embryonic days 12-15. In addition, starting at ED 12, we observed preferential accumulation of desmin in the vicinity of the myotendinous junction, a trend that did not change up to ED 15. Nerve terminal first appeared at ED 13 and formed regularly spaced linear arrays at the centre of the muscle fibre by ED 15. The results of immunohistochemical staining agreed with those of RT-PCR analysis. We found that desmin accumulated in the vicinity of the myotendinous junction starting at ED 12, prior to the onset of jaw movement. We speculate that the accumulation of desmin is due to factors other than mechanical stress experienced during early muscle contraction. Meanwhile, the time point at which nerve terminals first appeared roughly coincided with the onset of jaw movement. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

PubMed

Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

2015-04-20

What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Functional regeneration of the transected recurrent laryngeal nerve using a collagen scaffold loaded with laminin and laminin-binding BDNF and GDNF

PubMed Central

Wang, Baoxin; Yuan, Junjie; Chen, Xinwei; Xu, Jiafeng; Li, Yu; Dong, Pin

2016-01-01

Recurrent laryngeal nerve (RLN) injury remains a challenge due to the lack of effective treatments. In this study, we established a new drug delivery system consisting of a tube of Heal-All Oral Cavity Repair Membrane loaded with laminin and neurotrophic factors and tested its ability to promote functional recovery following RLN injury. We created recombinant fusion proteins consisting of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) fused to laminin-binding domains (LBDs) in order to prevent neurotrophin diffusion. LBD-BDNF, LBD-GDNF, and laminin were injected into a collagen tube that was fitted to the ends of the transected RLN in rats. Functional recovery was assessed 4, 8, and 12 weeks after injury. Although vocal fold movement was not restored until 12 weeks after injury, animals treated with the collagen tube loaded with laminin, LBD-BDNF and LBD-GDNF showed improved recovery in vocalisation, arytenoid cartilage angles, compound muscle action potentials and regenerated fibre area compared to animals treated by autologous nerve grafting (p < 0.05). These results demonstrate the drug delivery system induced nerve regeneration following RLN transection that was superior to that induced by autologus nerve grafting. It may have potential applications in nerve regeneration of RLN transection injury. PMID:27558932

Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.

PubMed Central

Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A

1992-01-01

The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1295858

Modelling the Effects of Electrical Coupling between Unmyelinated Axons of Brainstem Neurons Controlling Rhythmic Activity

PubMed Central

Hull, Michael J.; Soffe, Stephen R.; Willshaw, David J.; Roberts, Alan

2015-01-01

Gap junctions between fine unmyelinated axons can electrically couple groups of brain neurons to synchronise firing and contribute to rhythmic activity. To explore the distribution and significance of electrical coupling, we modelled a well analysed, small population of brainstem neurons which drive swimming in young frog tadpoles. A passive network of 30 multicompartmental neurons with unmyelinated axons was used to infer that: axon-axon gap junctions close to the soma gave the best match to experimentally measured coupling coefficients; axon diameter had a strong influence on coupling; most neurons were coupled indirectly via the axons of other neurons. When active channels were added, gap junctions could make action potential propagation along the thin axons unreliable. Increased sodium and decreased potassium channel densities in the initial axon segment improved action potential propagation. Modelling suggested that the single spike firing to step current injection observed in whole-cell recordings is not a cellular property but a dynamic consequence of shunting resulting from electrical coupling. Without electrical coupling, firing of the population during depolarising current was unsynchronised; with coupling, the population showed synchronous recruitment and rhythmic firing. When activated instead by increasing levels of modelled sensory pathway input, the population without electrical coupling was recruited incrementally to unpatterned activity. However, when coupled, the population was recruited all-or-none at threshold into a rhythmic swimming pattern: the tadpole “decided” to swim. Modelling emphasises uncertainties about fine unmyelinated axon physiology but, when informed by biological data, makes general predictions about gap junctions: locations close to the soma; relatively small numbers; many indirect connections between neurons; cause of action potential propagation failure in fine axons; misleading alteration of intrinsic firing properties. Modelling also indicates that electrical coupling within a population can synchronize recruitment of neurons and their pacemaker firing during rhythmic activity. PMID:25954930

Enterocyte-afferent nerve interactions in dietary fat sensing.

PubMed

Mansouri, A; Langhans, W

2014-09-01

The central nervous system (CNS) constantly monitors nutrient availability in the body and, in particular, in the gastrointestinal (GI) tract to regulate nutrient and energy homeostasis. Extrinsic parasympathetic and sympathetic nerves are crucial for CNS nutrient sensing in the GI tract. These extrinsic afferent nerves detect the nature and amount of nutrients present in the GI tract and relay the information to the brain, which controls energy intake and expenditure accordingly. Dietary fat and fatty acids are sensed through various direct and indirect mechanisms. These sensing processes involve the binding of fatty acids to specific G protein-coupled receptors expressed either on the afferent nerve fibres or on the surface of enteroendocrine cells that release gut peptides, which themselves can modulate afferent nerve activity through their cognate receptors or have endocrine effects directly on the brain. Further dietary fat sensing mechanisms that are related to enterocyte fat handling and metabolism involve the release of several possible chemical mediators such as fatty acid ethanolamides or apolipoprotein A-IV. We here present evidence for yet another mechanism that may be based on ketone bodies resulting from enterocyte oxidation of dietary fat-derived fatty acids. The presently available evidence suggests that sympathetic rather than vagal afferents are involved, but further experiments are necessary to critically examine this concept. © 2014 John Wiley & Sons Ltd.

Reflex tracheal contraction during pulmonary venous congestion in the dog.

PubMed Central

Kappagoda, C T; Man, G C; Ravi, K; Teo, K K

1988-01-01

1. The effect of pulmonary venous congestion on tracheal tone was studied in dogs anaesthetized with alpha-chloralose. Pulmonary venous congestion was produced by partial obstruction of the mitral valve to increase left atrial pressure by 10 mmHg. Tracheal tone was measured in vivo by an isometric force displacement method. 2. Tracheal tone increased by 6.3 +/- 0.3 g from a control level of 91.6 +/- 2.8 g when left atrial pressure was increased by 10.5 +/- 0.3 mmHg. This response was abolished by cooling the cervical vagi to 8 degrees C at a point caudal to the origin of the superior laryngeal nerves. Also, sectioning the superior laryngeal nerves abolished this increase in tracheal tone. 3. Afferent activity recorded from rapidly adapting receptors of the airways increased significantly during pulmonary venous congestion. This increase in activity was abolished by cooling the vagi caudal to the recording site to 8-9 degrees C. 4. Administration of propranolol (0.5 mg/kg) failed to abolish this increase in tracheal tone while atropine (3 mg/kg) did so. 5. Stimulation of left atrial receptors without an increase in left atrial pressure and stimulation of right atrial receptors with and without increases in right atrial pressure did not cause any change in tracheal tone. 6. It is suggested that pulmonary venous congestion is associated with a reflex increase in tracheal tone, the afferent limb of which is formed by pulmonary receptors discharging into myelinated fibres in the cervical vagi and the efferent limb by parasympathetic cholinergic fibres in the superior laryngeal nerves. The afferent receptors are likely to be the rapidly adapting receptors. This reflex may be of importance in the development of the respiratory symptoms associated with left ventricular failure. PMID:3236242

International Symposium on Electrets (ISE 6) (6th) Held in Oxford, England on 1-3 September 1988

DTIC Science & Technology

1988-09-01

detector Heat and other electromagnetic radiation detection Micro- & millimeter waves Nerve excitation studies Optical fibre attenuation Heat generation in...Phenomena in Reslnic Eaters of 241 Photothermoplastic Devices for Application to Holographic Optical Switching J. Datndurand, C. Lacabanne, J.Y. Molsan...328 Ionisation Chambers K. Doughty and I. Fleming t-64 Electro- Optical Behaviour of Ferroelectric Liquid 334 Crystal (FLC) Mixtures H.R. Dilbal, C

OCT for glaucoma diagnosis, screening and detection of glaucoma progression.

PubMed

Bussel, Igor I; Wollstein, Gadi; Schuman, Joel S

2014-07-01

Optical coherence tomography (OCT) is a commonly used imaging modality in the evaluation of glaucomatous damage. The commercially available spectral domain (SD)-OCT offers benefits in glaucoma assessment over the earlier generation of time domain-OCT due to increased axial resolution, faster scanning speeds and has been reported to have improved reproducibility but similar diagnostic accuracy. The capabilities of SD-OCT are rapidly advancing with 3D imaging, reproducible registration, and advanced segmentation algorithms of macular and optic nerve head regions. A review of the evidence to date suggests that retinal nerve fibre layer remains the dominant parameter for glaucoma diagnosis and detection of progression while initial studies of macular and optic nerve head parameters have shown promising results. SD-OCT still currently lacks the diagnostic performance for glaucoma screening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Transverse tripolar spinal cord stimulation: theoretical performance of a dual channel system.

PubMed

Struijk, J J; Holsheimer, J

1996-07-01

A new approach to spinal cord stimulation is presented, by which several serious problems of conventional methods can be solved. A transverse tripolar electrode with a dual-channel voltage stimulator is evaluated theoretically by means of a volume conductor model, combined with nerve fibre models. The simulations predict that a high degree of freedom in the control of activation of dorsal spinal pathways may be obtained with the described system. This implies an easier control of paraesthesia coverage of skin areas and the possibility to correct undesired paraesthesia patterns, caused by lead migration, tissue growth, or anatomical asymmetries, for example, without surgical intervention. It will also be possible to preferentially activate either dorsal column or dorsal root fibres, which has some important clinical advantages. Compared to conventional stimulation systems, the new system has a relatively high current drain.

Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones.

PubMed

Evstratova, Alesya; Tóth, Katalin

2011-12-01

The co-release of neuromodulatory substances in combination with classic neurotransmitters such as glutamate and GABA from individual presynaptic nerve terminals has the capacity to dramatically influence synaptic efficacy and plasticity. At hippocampal mossy fibre synapses vesicular zinc is suggested to serve as a cotransmitter capable of regulating calcium release from internal stores in postsynaptic CA3 pyramidal cells. Here we investigated this possibility using combined intracellular ratiometric calcium imaging and patch-clamp recording techniques. In acute hippocampal slices a brief train of mossy fibre stimulation produced a large, delayed postsynaptic Ca(2+) wave that was spatially restricted to the proximal apical dendrites of CA3 pyramidal cells within stratum lucidum. This calcium increase was sensitive to intracellularly applied heparin indicating reliance upon release from internal stores and was triggered by activation of both group I metabotropic glutamate and NMDA receptors. Importantly, treatment of slices with the membrane-impermeant zinc chelator CaEDTA did not influence the synaptically evoked postsynaptic Ca(2+) waves. Moreover, mossy fibre stimulus evoked postsynaptic Ca(2+) signals were not significantly different between wild-type and zinc transporter 3 (ZnT3) knock-out animals. Considered together our data do not support a role for vesicular zinc in regulating mossy fibre evoked Ca(2+) release from CA3 pyramidal cell internal stores.

Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones

PubMed Central

Evstratova, Alesya; Tóth, Katalin

2011-01-01

Abstract The co-release of neuromodulatory substances in combination with classic neurotransmitters such as glutamate and GABA from individual presynaptic nerve terminals has the capacity to dramatically influence synaptic efficacy and plasticity. At hippocampal mossy fibre synapses vesicular zinc is suggested to serve as a cotransmitter capable of regulating calcium release from internal stores in postsynaptic CA3 pyramidal cells. Here we investigated this possibility using combined intracellular ratiometric calcium imaging and patch-clamp recording techniques. In acute hippocampal slices a brief train of mossy fibre stimulation produced a large, delayed postsynaptic Ca2+ wave that was spatially restricted to the proximal apical dendrites of CA3 pyramidal cells within stratum lucidum. This calcium increase was sensitive to intracellularly applied heparin indicating reliance upon release from internal stores and was triggered by activation of both group I metabotropic glutamate and NMDA receptors. Importantly, treatment of slices with the membrane-impermeant zinc chelator CaEDTA did not influence the synaptically evoked postsynaptic Ca2+ waves. Moreover, mossy fibre stimulus evoked postsynaptic Ca2+ signals were not significantly different between wild-type and zinc transporter 3 (ZnT3) knock-out animals. Considered together our data do not support a role for vesicular zinc in regulating mossy fibre evoked Ca2+ release from CA3 pyramidal cell internal stores. PMID:21986206

Handlebar palsy--a compression syndrome of the deep terminal (motor) branch of the ulnar nerve in biking.

PubMed

Capitani, Daniel; Beer, Serafin

2002-10-01

We describe 3 patients who developed a severe palsy of the intrinsic ulnar supplied hand muscles after bicycle riding. Clinically and electrophysiologically all showed an isolated lesion of the deep terminal motor branch of the ulnar nerve leaving the hypothenar muscle and the distal sensory branch intact. This type of lesion at the canal of Guyon is quite unusual, caused in the majority of cases by chronic external pressure over the ulnar palm. In earlier reports describing this lesion in bicycle riders, most patients experienced this lesion after a long distance ride. Due to the change of riding position and shape of handlebars (horn handle) in recent years, however, even a single bicycle ride may be sufficient to cause a lesion of this ulnar branch. Especially in downhill riding, a large part of the body weight is supported by the hand on the corner of the handlebar leading to a high load at Guyon's canal. As no sensory fibres are affected, the patients are not aware of the ongoing nerve compression until a severe lesion develops. Individual adaptation of the handlebar and riding position seems to be crucial for prevention of this type of nerve lesion.

Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

PubMed

Udina, Esther; Putman, Charles T; Harris, Luke R; Tyreman, Neil; Cook, Victoria E; Gordon, Tessa

2017-03-01

Smn +/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/- transgenic mouse increases their susceptibility to cell death demonstrated that all the motoneurons survived and they sustained their capacity to regenerate their nerve fibres. It is concluded the systematic die-back of motoneurons that innervate both fast- and slow-twitch muscle fibres is not related to immaturity of the neuromuscular system in SMA. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Localization of soluble guanylate cyclase activity in the guinea pig inner ear.

PubMed

Takumida, M; Anniko, M; Popa, R; Zhang, D M

2000-01-01

The aim of this study was to characterize the nitric oxide (NO) receptor soluble guanylate cyclase (sGC), to determine the cells targeted by NO and to elucidate the function of the NO/cGMP pathway in the inner ear. sGC activity in the inner ear was localized by immunohistochemical detection of NO-stimulated cGMP. Soluble guanylate cyclase activity in the cochlea was detected in the nerve endings underneath the outer and inner hair cells, supporting cells, stria vascularis and vessels. In the vestibular organs, sGC activity was detected in the cytoplasm of sensory cells, nerve fibres, dark cells and transitional cells and vessels. These findings suggest that the NO/cGMP pathway may be involved in regulatory processes in neurotransmission, blood flow and inner ear fluid homeostasis.

Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study.

PubMed

Chinnery, Holly R; Naranjo Golborne, Cecilia; Downie, Laura E

2017-07-01

To investigate whether oral, long-chain omega-3 (ω-3) essential fatty acid (EFA) supplementation, for 3 months, induces changes to the central corneal sub-basal nerve plexus in dry eye disease and whether nerve alterations correlate with clinical findings. This prospective, comparative study involved the final 12 participants enrolled in a randomised, double-masked, placebo-controlled clinical trial of 60 participants with moderate dry eye disease. Participants received either placebo (olive oil 1500 mg/day; n = 4) or ω-3 EFA supplements (~1000 mg/day eicosapentaenoic acid + ~500 mg/day docosahexaenoic acid; n = 8) for 90 days. The main outcome measure was the mean change in central corneal sub-basal plexus nerve parameters between days one and 90, quantified using in vivo confocal microscopy. Secondary outcomes included mean change in tear osmolarity, corneal dendritic cell density and basal epithelial cell density. Compared with baseline, the reduction in OSDI score and tear osmolarity at day 90 were greater in the ω-3 EFA group than the placebo group (OSDI: ω-3 EFA, mean ± SEM: -15.6 ± 2.8 vs placebo: -2.8 ± 4.1 units, t 5 = 2.6, p = 0.04; tearosmolarity: ω-3 EFA: -22.63 ± 5.7 vs placebo: -8 ± 2.7 mOsmol/L, t 9 = 2.3, p = 0.04). At day 90, corneal total nerve branch density (CTBD: 91.1 ± 8.6 vs 45.1 ± 13.4 branches/mm 2 , F 1,10 = 14, p = 0.004) and corneal nerve branch density on the main fibre (CNBD: 63.4 ± 6.5 vs 27.9 ± 11.5 branches/mm 2 , F 1,10 = 6, p = 0.03) were higher in the ω-3 EFA group compared with placebo. Relative to day 1, CNBD (branches/mm 2 ) increased at day 90 in the ω-3 EFA group (+20.0 ± 9.2, t 8 = 3.2 p = 0.01) compared with placebo (-10.8 ± 3.2). Similar changes were evident for corneal nerve fibre length (CNFL, mm/mm 2 ), which increased from baseline at day 90 in the omega-3 EFA group (+2.9 ± 1.6, t 8 = 3.4 p = 0.01) compared with placebo (-2.7 ± 0.5). There was a negative correlation between CTBD and tear osmolarity (r 10 = -0.70, p = 0.01). No significant changes were observed for basal epithelial cell or corneal dendritic cell density. These pilot study findings suggest that ω-3 EFA supplementation imparts neuroprotective effects in the corneal sub-basal plexus that correlate with the extent of tear osmolarity normalisation. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

[Neurologic Complications in HPV Vaccination].

PubMed

Ikeda, Shu-ichi

2015-07-01

A relatively high incidence of chronic limb pain, frequently complicated by violent, tremulous involuntary movements, has been noted in Japanese girls following human papillomavirus vaccination. The average incubation period after the first dose of the vaccine was 5.47 ± 5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the feet, limb pain, and weakness. The skin temperature of the girls with limb symptoms was slightly lower in the fingers and moderately lower in the toes. Digital plethysmograms revealed a reduced peak of the waves, especially in the toes. Limb symptoms of the affected girls were compatible with the diagnostic criteria for complex regional pain syndrome. The Schellong test identified a significant number of patients with orthostatic hypotension and a few with postural orthostatic tachycardia syndrome. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the patients was psychosomatic disease. Recently, delayed manifestation of cognitive dysfunction in the post-vaccinated girls has attracted attention. The symptoms include memory loss and difficulty in reading textbooks and/or calculation.

Evidence from the use of vibration during procaine nerve block that the spindle group II fibres contribute excitation to the tonic stretch reflex of the decerebrate cat

PubMed Central

McGrath, G. J.; Matthews, P. B. C.

1973-01-01

1. Experiments have been performed to test the hypothesis that the group II fibres from the secondary endings of the muscle spindle provide an excitatory contribution to the tonic stretch reflex of the decerebrate cat. They have consisted of studying the effect of fusimotor paralysis by procaine, applied to the muscle nerve, on the reflex response to the combined stimuli of stretch (5-9 mm at 5 mm/sec) and of high-frequency vibration (100-150 Hz, 150 μm). 2. The reflex response to the combined stimuli was found to be paralysed in two distinct stages which paralleled those of the ordinary stretch reflex described earlier. The two phases of paralysis may be attributed to an early paralysis of the γ efferents followed by a later paralysis of the Ia afferents and α motor fibres. However, the Ia discharges elicited by the combined stimuli, unlike those elicited by simple stretch, should have remained unchanged on γ efferent paralysis since the Ia firing frequency may be presumed to have been clamped at the vibration frequency by the occurrence of one-to-one `driving'. The early reduction of the response to the combined stimuli may thus be attributed to the removal of a stretchevoked autogenetic excitatory input other than that long known to be provided by the Ia pathway. This supports the view that the spindle group II fibres have such an action, since their firing will be appropriately reduced on γ efferent paralysis by removal of their pre-existing fusimotor bias; there is no evidence for the existence of any other group of fibres with the right properties. 3. Recording of compound action potentials and of single units confirmed the great sensitivity of the γ efferents to procaine but showed that the group II fibres were nearly as resistant as the Ia fibres and α motor fibres. 4. The reliability of one-to-one driving of the Ia discharges by the vibration was tested in control experiments in which the reflex was elicited by an asymmetrical vibratory waveform with a rapid rising phase (1·5 or 1·9 msec at 140 Hz) and a slower falling phase. Recordings from single units showed that the use of this wave form greatly diminished any tendency to double driving (2 spikes/cycle of vibration) during the dynamic phase of stretch and never elicited it during the static phase of stretch when the reflex measurements were made. These `pulsed' vibrations elicited reflex contractions which were of the same general size and which were paralysed in the same two phases by procaine as those elicited by sinusoidal vibrations. This eliminates the possibility that the early phase of paralysis might have been due to conversion of the pattern of Ia firing from double to single driving on γ efferent paralysis. 5. Wedensky inhibition of the afferent fibres could not be held responsible for the early phase of paralysis. 6. The results are taken to strengthen the hypothesis that the spindle group II fibres contribute excitation rather than inhibition to the stretch reflex. The particular support derived from the present experiments is that all measurements of the size of the reflex at various times were made with the muscle at the same length so that the findings cannot be attributed to the tension-length properties of muscle. The detailed mechanism of the excitation, however, remains to be established and certain of the present findings suggest that it may not be a direct one. PMID:4271734

Comparative quantitative study of astrocytes and capillary distribution in optic nerve laminar regions.

PubMed

Balaratnasingam, Chandrakumar; Kang, Min H; Yu, Paula; Chan, Geoffrey; Morgan, William H; Cringle, Stephen J; Yu, Dao-Yi

2014-04-01

Retinal ganglion cell (RGC) axonal structure and function in the optic nerve head (ONH) is predominantly supported by astrocytes and capillaries. There is good experimental evidence to demonstrate that RGC axons are perturbed in a non-uniform manner following ONH injury and it is likely that the pattern of RGC axonal modification bears some correlation with the quantitative properties of astrocytes and capillaries within laminar compartments. Although there have been some excellent topographic studies concerning glial and microvascular networks in the ONH our knowledge regarding the quantitative properties of these structures are limited. This report is an in-depth quantitative, structural analysis of astrocytes and capillaries in the pre laminar, lamina cribrosa and post laminar compartments of the ONH. 49 optic nerves from human (n = 10), pig (n = 12), horse (n = 6), rat (n = 11) and rabbit (n = 10) eyes are studied. Immunohistochemical and high-magnification confocal microscopy techniques are used to co-localise astrocytes, capillaries and nuclei in the mid-portion of the optic nerve. Quantitative methodology is used to determine the area occupied by astrocyte processes, microglia processes, nuclei density and the area occupied by capillaries in each laminar compartment. Comparisons are made within and between species. Relationships between ONH histomorphometry and astrocyte-capillary constitution are also explored. This study demonstrates that there are significant differences in the quantitative properties of capillaries and astrocytes between the laminar compartments of the human ONH. Astrocyte processes occupied the greatest area in the lamina cribrosa compartment of the human ONH implicating it as an area of great metabolic demands. Microglia were found to occupy only a small proportion of tissue in the rat, rabbit and pig optic nerve suggesting that the astrocyte is the predominant glia cell type in the optic nerve. This study also demonstrates that there is significant uniformity, with respect to astrocyte and capillary constitution, in the post laminar region of species with an unmyelinated anterior optic nerve. This implicates an important role served by oligodendrocytes and myelin in governing the structural characteristics of the post laminar optic nerve. Finally, this study demonstrates that eyes with similar lamina cribrosa structure do not necessarily share an identical cellular constitution with respect to astrocytes. The quantitative properties of astrocytes in the pre laminar and lamina cribrosa regions of the rat, which has a rudimentary lamina cribrosa with only a few collagenous beams, shared more similarities to the human eye than the pig or horse. The quantitative properties of astrocytes and capillaries in the laminar compartments of the ONH provide a basis for understanding the pathogenic mechanisms that are involved in diseases such as glaucoma and ischemic optic neuropathy. The findings in this study also provide valuable information about the distinct advantages of different animal models for studying human optic nerve diseases. Utilisation of structural data provided in this report together with emerging in vivo technology may potentially permit the early identification of RGC axonal injury by quantifying changes in ONH capillaries and astrocytes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with chronic cough and preserved muscle stretch reflexes: evidence for selective sparing of afferent Ia fibres.

PubMed

Infante, Jon; García, Antonio; Serrano-Cárdenas, Karla M; González-Aguado, Rocío; Gazulla, José; de Lucas, Enrique M; Berciano, José

2018-06-01

The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Established clinical picture included severe hypopallesthesia predominating in the lower limbs with postural imbalance, and variable degree of cerebellar axial and appendicular ataxia, dysarthria and horizontal gaze-evoked nystagmus. Upper- and lower-limb tendon jerks were preserved, whereas jaw jerk was absent. Vestibular function testing showed bilateral impairment of the vestibulo-ocular reflex. Nerve conduction studies demonstrated normal motor conduction parameters and absence or severe attenuation of sensory nerve action potentials. Somatosensory evoked potentials were absent or severely attenuated. Biceps and femoral T-reflex recordings were normal, while masseter reflex was absent or attenuated. Sympathetic skin responses were normal. Cranial MRI showed vermian and hemispheric cerebellar atrophy predominating in lobules VI, VII and VIIa. We conclude that spasmodic cough may be an integral part of the clinical picture in CANVAS, antedating the appearance of imbalance in several decades and that sparing of muscle spindle afferents (Ia fibres) is probably the pathophysiological basis of normoreflexia.

A comparative study on the distribution of non-specific esterase amongst the various constituents of retinas of some vertebrates.

PubMed

Tyagi, H R; Tewari, H B

1979-01-01

A wide coverage of the retinae of a large number of animals (Calotes, Varanus, Naja, Athene, Passer, Streptopelia, Psittacula and Funambulus) from the point of view of the histoenzymological distribution of non-specific esterase amongst the various constituents reveals mostly identical patterns. They are as follows: 1. Outer segments - positive in all cases. 2. Outer plexiform layer - equipped with enzymatic activity in all the instances. 3. Inner nuclear layer - thin cytoplasmic rim of the neurons characterized by positive activity; the nuclei of the neurons are completely negative. 4. Inner plexiform layer - this layer is endowed with the enzymatic activity. 5. Ganglion cells - negative in all cases. 6. Nerve fibres of the layer of nerve fibres, situated adjasent to ganglion cells are positive in all the animals; in case of squirrel oligodandroglial cells present in the region have demonstrated activity of a high order. On of the high-lights of the present contribution is demarcation of the inner plexiform layer into three stratified zones, equipped with enzymatic activity in Calotes, Streptopelia, Naja and Funambulus. Such stratifications are not seen in Varanus, Passer and Psittacula. The significance of the various patterns and the equipment of the enzyme in various constituents at various locals have been discussed in relation to the metabolic functions, zone-wise and interzone-wise in visual processes of various animals.

Specificity in monosynaptic and disynaptic bulbospinal connections to thoracic motoneurones in the rat

PubMed Central

de Almeida, Anoushka T R; Kirkwood, Peter A

2013-01-01

The respiratory activity in the intercostal nerves of the rat is unusual, in that motoneurones of both branches of the intercostal nerves, internal and external, are activated during expiration. Here, the pathways involved in that activation were investigated in anaesthetised and in decerebrate rats by cross-correlation and by intracellular spike-triggered averaging from expiratory bulbospinal neurones (EBSNs), with a view to revealing specific connections that could be used in studies of experimental spinal cord injury. Decerebrate preparations, which showed the strongest expiratory activity, were found to be the most suitable for these measurements. Cross-correlations in these preparations showed monosynaptic connections from 16/19 (84%) of EBSNs, but only to internal intercostal nerve motoneurones (24/37, 65% of EBSN/nerve pairs), whereas disynaptic connections were seen for external intercostal nerve motoneurones (4/19, 21% of EBSNs or 7/25, 28% of EBSN/nerve pairs). There was evidence for additional disynaptic connections to internal intercostal nerve motoneurones. Intracellular spike-triggered averaging revealed excitatory postsynaptic potentials, which confirmed these connections. This is believed to be the first report of single descending fibres that participate in two different pathways to two different groups of motoneurones. It is of interest compared with the cat, where only one group of motoneurones is activated during expiration and only one of the pathways has been detected. The specificity of the connections could be valuable in studies of plasticity in pathological situations, but care will be needed in studying connections in such situations, because their strength was found here to be relatively weak. PMID:23774278

Repair of nerve injury by implanting prostheses obtained from isogenic acellular nerve segments.

PubMed

García-Medrano, B; Mesuro Domínguez, N; Simón Pérez, Cl; Garrosa García, M; Gayoso Del Villar, S; Mayo Íscar, A; Gayoso Rodríguez, M J; Martín Ferrero, M A

When a nerve section with a significant gap occurs, it is necessary to use a prosthesis to suture it. To date an autologous nerve segment graft appears to be the best treatment; but it has several important disadvantages. Our goal is to study the effectiveness of an isogenic acellular nerve prosthesis comparing a simple suture with tubulisation. Four groups of Wistar rats were used. The animals in Group 0 served as donors of nerve segments to graft. Group 1 received the implant with an end-to-end suture. In group 2, the implant was sutured inside an ɛ-caprolactone tube. Group 3 received it in a polylactic-co-glycolic acid tube. We evaluated the motor function (sciatic index and step test in motion), and the regeneration length by histological study of regeneration, after a maximum of 3 weeks. Regeneration was uneven in the three groups. In all groups, there were implants with regenerated nerve fibres at the maximum studied length (15mm) and others where regeneration was scarce. The mean regeneration length was greater in the direct end-to-end suture group (G1), although the regeneration speed was similar in the three groups. Group 1 showed the highest percentage of regeneration, but the variability of results prevents this difference reaching statistical significance. We found no significant differences between the two groups with polymer tubes. For the implantation of isogenic acellular nerve prosthesis, under our experimental conditions, the direct end-to-end suture was more effective than when it isprotected with biopolymer tubes. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Reflex control of discharge in motor fibres to the larynx

PubMed Central

Głogowska, Maria; Stransky, A.; Widdicombe, J. G.

1974-01-01

1. Action potentials have been recorded from single laryngeal motor fibres, with expiratory or inspiratory phases, in cats anaesthetized with pentobarbitone and breathing through a tracheal cannula. 2. Pneumothorax increased the discharge of both inspiratory and expiratory units, the inspiratory response being greatly reduced by bilateral vagotomy below the origin of the recurrent laryngeal nerves. 3. Addition of a `viscous' resistance to breathing, or asphyxial rebreathing through an added dead space, increased the activity of inspiratory units and decreased that of expiratory units. 4. Induction of pulmonary oedema decreased the discharge of inspiratory units and increased that of expiratory units. After vagotomy the response of inspiratory units was reversed. 5. Intravenous injections of potassium cyanide increased the activity of both types of unit. 6. Chemical irritation of the laryngeal mucosa decreased the discharge of inspiratory units and increased that of expiratory units, whether the vagi were intact or cut. 7. It is concluded that expiratory unit discharge can be correlated with expiratory laryngeal resistance, but that inspiratory unit discharge does not correlate so well with inspiratory laryngeal resistance. 8. The relationship between laryngeal motor-fibre activity and the contractions of the inspiratory and expiratory muscles of breathing is discussed. PMID:4415512

Quantitative analysis of laryngeal mechanosensitivity in the cat and rabbit.

PubMed Central

Davis, P J; Nail, B S

1987-01-01

1. Single afferent fibres in the internal branch of the superior laryngeal nerve which responded to light touch or gentle probing of discrete areas of the exposed epithelium of the opened larynx were identified in anaesthetized, paralysed cats (148 fibres) and rabbits (58 fibres). 2. A quantitative examination of the sensitivity of these laryngeal mechanoreceptors to both static (step indentations) and dynamic (vibratory) forms of mechanical stimulation was undertaken using a servo-controlled mechanical stimulator. 3. In both species two predominant classes of mechanoreceptors were observed (Boushey, Richardson, Widdicombe & Wise, 1974). One class was distinguished by a regular and continuous pattern of activity at a frequency of 10-70 Hz (tonic fibres, sixty-six in cat, thirty-five in rabbit). The other class was silent or (more rarely) irregularly active at a very low frequency (silent fibres, eighty-two in cat, twenty-three in rabbit). 4. The location of the receptive fields was determined by manual probing. Inter-species and regional variations in receptive field location were observed for the two fibre groups. 5. Conduction velocity was measured for twenty-one tonic and seven silent fibres in the rabbit by a pre-triggered averaging technique. The results obtained (tonic: range 10.8-30.0, mean +/- S.E. of mean 21.4 +/- 1.2 m/s; silent: 14.8-28.6, 20.4 +/- 1.8 m/s) were characteristic of group III afferent fibres but were not significantly different for the two classes. 6. Both classes of receptor showed a response at the onset of a step indentation of the region of the mucosa that corresponded to their receptive field. Subsequent to this brief initial response the behaviour of the two classes diverged markedly. Tonic fibres were invariably slowly adapting whereas most (forty-four out of fifty-five in cat; twenty-two out of twenty-three in rabbit) silent fibres were rapidly adapting, at least for smaller indentation amplitudes. 7. Receptors of both classes were readily entrained to discharge at the same frequency as the probe stimulator (1:1 entrainment) when this was made to vibrate upon the receptive area for test periods of 0.5 or 1.0 s. Tuning curves were constructed of the minimum amplitudes required to elicit 1:1 entrainment throughout an entire test period at various frequencies. 8. Individual fibres in the two classes could be entrained at frequencies up to 400 Hz or more at sensitive (e.g. less than 100 microns) vibratory amplitudes. However, all fibres were less sensitive at these higher frequencies than at some lower point on the frequency scale.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3656197

Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

PubMed Central

Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

2014-01-01

Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using minocycline to treat diabetic neuropathy. PMID:25158309

A new promising simultaneous approach for attenuating type II diabetes mellitus induced neuropathic pain in rats: iNOS inhibition and neuroregeneration.

PubMed

Ahlawat, Abhilasha; Sharma, Saurabh

2018-01-05

In view of the pathologic basis for the treatment of diabetic neuropathy, it is important to enhance nerve regeneration as well as prevent nerve degeneration. So, in the present study, we have investigated the effect of S-Methylisothiourea Sulfate (selective iNOS inhibitor) and Citicoline, alone and in combination, on Type II diabetes mellitus induced neuropathic pain in wistar rats. Type II diabetes was induced by providing high fat diet and low dose of Streptozotocin for 35 days in rats. Type II diabetes mellitus was assessed in terms of increased glucose, triglycerides, cholesterol, LDL levels, glucose tolerance and decrease in HDL levels. Neuropathy as the complication of type II diabetes was assessed in terms of decreased nerve conduction velocity, mechanical and thermal hyperalgesia and cold allodynia. Oxidative stress was assessed in sciatic nerve and showed increase in LPO and nitrite levels whereas decrease was shown in GSH and catalase activity. Axonal degeneration marked by nerve fibre dearrangement and demyelination was observed in histopathological studies. SMT (iNOS inhibitor), Citicoline and low dose combination of both drugs significantly attenuates the diabetic neuropathic pain assessed in terms of parameters employed. Thus, it may be concluded that simultaneous administration of SMT and Citicoline may provide potential therapeutics for diabetic neuropathic pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Substance P stimulates sphincter of Oddi motility and inhibits trans-sphincteric flow in the Australian brush-tailed possum.

PubMed

Cox, M R; Padbury, R T; Harvey, J R; Baker, R A; Toouli, J; Saccone, G T

1998-04-01

Substance P containing nerves are widely distributed throughout the gastrointestinal tract. The aims of this study were to determine the distribution of substance P containing nerves in the extrahepatic biliary tree of the Australian brush-tailed possum and to characterize the effect of exogenous substance P on the sphincter of Oddi (SO) motility and transphincteric flow in vivo. Immunohistochemical staining of fixed specimens (n = 8) found moderate numbers of substance P containing nerve cell bodies and fibres throughout the neural plexuses of the SO, in particular in the serosal and intraluminal nerve trunks of the SO and gallbladder. Synthetic porcine substance P (1-2000 ng kg-1), administered by close intra-arterial injection (i.a.; n = 7), produced a dose-dependent elevation in basal pressure [P < 0.01] and an associated dose-dependent reduction in trans-sphincteric flow [P < 0.0001]. Substance P had no significant dose-dependent effect on SO phasic contraction amplitude or frequency. Tetrodotoxin (9 micrograms kg-1, i.a.) did not inhibit the effect of substance P on SO motility and trans-sphincteric flow (n = 5). In conclusion, substance P containing nerves are found throughout the possum extrahepatic biliary tree. Exogenous substance P stimulates SO motility and reduces trans-sphincteric flow in vivo by acting directly on the sphincter smooth muscle.

Selective depolarization of the muscle membrane in frog nerve-muscle preparations by a chromatographically purified extract of the dinoflagellate Ostreopsis lenticularis

PubMed Central

Meunier, Frédéric A; Mercado, José A; Molgó, Jordi; Tosteson, Thomas R; Escalona de Motta, Gladys

1997-01-01

The actions of a chromatographically identified extract of the marine dinoflagellate Ostreopsis lenticularis, named ostreotoxin-3 (OTX-3), were studied on frog isolated neuromuscular preparations. OTX-3 (1–10 μg ml−1) applied to cutaneous pectoris nerve-muscle preparations depolarized skeletal muscle fibres and caused spontaneous contractions. The depolarization was neither reversed by prolonged washing nor by (+)-tubocurarine. OTX-3 decreased the amplitude of miniature end plate potentials (m.e.p.ps) but did not affect their frequency. Extracellular recording of compound action potentials revealed that OTX-3 affected neither excitability nor conduction along intramuscular nerve branches. End-plate potentials (e.p.ps) elicited by nerve stimulation were reduced in amplitude by OTX-3 and even showed reversed polarity in junctions deeply depolarized by the toxin. Membrane depolarization induced by OTX-3 was decreased about 70% in muscles pretreated for 30 min with 10 μM tetrodotoxin. In contrast, muscles pretreated with 5 μM μ-conotoxin GIIIA were completely insensitive to OTX-3-induced depolarization. OTX-3 did not affect e.p.p. amplitude and the quantal content of e.p.ps in junctions in which muscle depolarization was abolished by μ-conotoxin GIIIA. OTX-3 is a novel type of sodium-channel activating toxin that discriminates between nerve and skeletal muscle membranes. PMID:9249261

Neuroimmunophilin Ligands Protect Cavernous Nerves after Crush Injury in the Rat: New Experimental Paradigms

PubMed Central

Valentine, Heather; Chen, Yi; Guo, Hongzhi; McCormick, Jocelyn; Wu, Yong; Sezen, Sena F.; Hoke, Ahmet; Burnett, Arthur L.; Steiner, Joseph P.

2009-01-01

Objectives We investigated the effects of the orally bioavailable non-immunosuppressive immunophilin ligand GPI 1046 (GPI) on erectile function and cavernous nerve (CN) histology following unilateral or bilateral crush injury (UCI, BCI, respectively) of the CNs. Methods Adult male Sprague-Dawley rats were administered GPI 15 mg/kg intraperitoneally (ip) or 30 mg/kg orally (po), FK506 1 mg/kg, ip, or vehicle controls for each route of administration just prior to UCI or BCI and daily up to 7 d following injury. At day 1 or 7 of treatment, erectile function induced by CN electrical stimulation was measured, and electron microscopic analysis of the injured CN was performed. Results Intraperitoneal administration of GPI to rats with injured CN protected erectile function, in a fashion similar to the prototypic immunophilin ligand FK506, compared with vehicle-treated animals (93% ± 9% vs. 70% ± 5% vs. 45% ± 1%, p < 0.01, respectively). Oral administration of GPI elicited the same level of significant protection from CN injury. GPI administered PO at 30 mg/kg/d, dosing either once daily or four times daily with 7.5 mg/kg, provided nearly complete protection of erectile function. In a more severe BCI model, PO administration of GPI maintained erectile function at 24 h after CN injury. Ultrastructural analysis of injured CNs indicated that GPI administered at the time of CN injury prevents degeneration of about 83% of the unmyelinated axons at 7 d after CN injury. Conclusions The orally administered immunophilin ligand GPI neuroprotects CNs and maintains erectile function in rats under various conditions of CN crush injury. PMID:17145129

Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

PubMed Central

2011-01-01

Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate. PMID:21619592

Biology of Schwann cells.

PubMed

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

2013-01-01

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

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.

Altered walking strategy and increased unsteadiness in participants with impaired glucose tolerance and Type 2 diabetes relates to small-fibre neuropathy but not vitamin D deficiency.

PubMed

Almurdhi, M M; Brown, S J; Bowling, F L; Boulton, A J M; Jeziorska, M; Malik, R A; Reeves, N D

2017-06-01

To investigate alterations in walking strategy and dynamic sway (unsteadiness) in people with impaired glucose tolerance and people with Type 2 diabetes in relation to severity of neuropathy and vitamin D levels. A total of 20 people with Type 2 diabetes, 20 people with impaired glucose tolerance and 20 people without either Type 2 diabetes or impaired glucose tolerance (control group) underwent gait analysis using a motion analysis system and force platforms, and detailed assessment of neuropathy and serum 25 hydroxy-vitamin D levels. Ankle strength (P = 0.01) and power (P = 0.003) during walking and walking speed (P = 0.008) were preserved in participants with impaired glucose tolerance but significantly lower in participants with Type 2 diabetes compared with control participants; however, step width (P = 0.005) and dynamic medio-lateral sway (P = 0.007) were significantly higher and posterior maximal movement (P = 0.000) was lower in participants with impaired glucose tolerance, but preserved in those with Type 2 diabetes compared with the control group. Dynamic medio-lateral sway correlated with corneal nerve fibre length (P = 0.001) and corneal nerve branch density (P = 0.001), but not with vibration perception threshold (P = 0.19). Serum 25 hydroxy-vitamin D levels did not differ significantly among the groups (P = 0.10) and did not correlate with any walking variables or measures of dynamic sway. Early abnormalities in walking strategy and dynamic sway were evident in participants with impaired glucose tolerance, whilst there was a reduction in ankle strength, power and walking speed in participants with Type 2 diabetes. Unsteadiness correlated with small-, but not large-fibre neuropathy and there was no relationship between vitamin D levels and walking variables. © 2017 Diabetes UK.

Nervous control of fish swimbladders.

PubMed

Nilsson, Stefan

2009-01-01

The swimbladder of teleost fish receives a rich and complex innervation by nerve fibres of the autonomic nervous system. While an understanding of the form and function of a non-adrenergic, non-cholinergic innervation is slowly emerging, the pattern of control by the "classical" cholinergic and adrenergic innervation is becoming relatively well understood. This short review describes the autonomic innervation patterns, and attempts to summarise the role of cholinergic and adrenergic pathways in the control of gas secretion and resorption in the teleost swimbladder.

Navigation-guided optic canal decompression for traumatic optic neuropathy: Two case reports.

PubMed

Bhattacharjee, Kasturi; Serasiya, Samir; Kapoor, Deepika; Bhattacharjee, Harsha

2018-06-01

Two cases of traumatic optic neuropathy presented with profound loss of vision. Both cases received a course of intravenous corticosteroids elsewhere but did not improve. They underwent Navigation guided optic canal decompression via external transcaruncular approach, following which both cases showed visual improvement. Postoperative Visual Evoked Potential and optical coherence technology of Retinal nerve fibre layer showed improvement. These case reports emphasize on the role of stereotactic navigation technology for optic canal decompression in cases of traumatic optic neuropathy.

Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands.

PubMed

Seifert, P; Spitznas, M

1999-06-01

This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin-Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor. Copyright 1999 Academic Press.

Metabolic effects of portal vein sensing.

PubMed

Mithieux, G

2014-09-01

The extrinsic gastrointestinal nerves are crucial in the sensing of nutrients and hormones and its translation in terms of control of food intake. Major macronutrients like glucose and protein are sensed by the extrinsic nerves located in the portal vein walls, which signal to the brain and account for the satiety phenomenon they promote. Glucose is sensed in the portal vein by neurons expressing the glucose receptor SGLT3, which activate the main regions of the brain involved in the control of food intake. Proteins indirectly act on food intake by inducing intestinal gluconeogenesis and its sensing by the portal glucose sensor. The mechanism involves a prior antagonism by peptides of the μ-opioid receptors present in the portal vein nervous system and a reflex arc with the brain inducing intestinal gluconeogenesis. In a comparable manner, short-chain fatty acids produced from soluble fibre act via intestinal gluconeogenesis to exert anti-obesity and anti-diabetic effects. In the case of propionate, the mechanism involves a prior activation of the free fatty acid receptor FFAR3 present in the portal nerves and a reflex arc initiating intestinal gluconeogenesis. © 2014 John Wiley & Sons Ltd.

Intralaryngeal neuroanatomy of the recurrent laryngeal nerve of the rabbit

PubMed Central

Ryan, Stephen; McNicholas, Walter T; O'Regan, Ronan G; Nolan, Philip

2003-01-01

We undertook this study to determine the detailed neuroanatomy of the terminal branches of the recurrent laryngeal nerve (RLN) in the rabbit to facilitate future neurophysiological recordings from identified branches of this nerve. The whole larynx was isolated post mortem in 17 adult New Zealand White rabbits and prepared using a modified Sihler's technique, which stains axons and renders other tissues transparent so that nerve branches can be seen in whole mount preparations. Of the 34 hemi-laryngeal preparations processed, 28 stained well and these were dissected and used to characterize the neuroanatomy of the RLN. In most cases (23/28) the posterior cricoarytenoid muscle (PCA) was supplied by a single branch arising from the RLN, though in five PCA specimens there were two or three separate branches to the PCA. The interarytenoid muscle (IA) was supplied by two parallel filaments arising from the main trunk of the RLN rostral to the branch(es) to the PCA. The lateral cricoarytenoid muscle (LCA) commonly received innervation from two fine twigs branching from the RLN main trunk and travelling laterally towards the LCA. The remaining fibres of the RLN innervated the thyroarytenoid muscle (TA) and comprised two distinct branches, one supplying the pars vocalis and the other branching extensively to supply the remainder of the TA. No communicating anastomosis between the RLN and superior laryngeal nerve within the larynx was found. Our results suggest it is feasible to make electrophysiological recordings from identified terminal branches of the RLN supplying laryngeal adductor muscles separate from the branch or branches to the PCA. However, the very small size of the motor nerves to the IA and LCA suggests that it would be very difficult to record selectively from the nerve supply to individual laryngeal adductor muscles. PMID:12739619

Intraspinal release of immunoreactive calcitonin gene-related peptide during development of inflammation in the joint in vivo--a study with antibody microprobes in cat and rat.

PubMed

Schaible, H G; Freudenberger, U; Neugebauer, V; Stiller, R U

1994-10-01

This study addressed the intraspinal release of immunoreactive calcitonin gene-related peptide in vivo during mechanical stimulation of the normal joint and during the development of an acute experimental inflammation in the knee joint in the anaesthetized cat (spinalized) and rat (not spinalized). Release was assessed using microprobes coated with antibody to calcitonin gene-related peptide; inhibition of binding of [125I]calcitonin gene-related peptide to these probes following insertion into the spinal cord is equated with intraspinal release of the endogenous (unlabelled) peptide. Probes inserted prior to inflammation showed marked basal release of immunoreactive calcitonin gene-related peptide in the dorsal horn with a maximum in the superficial dorsal horn in the absence of intentional stimulation. The pattern of binding of [125I]calcitonin gene-related peptide was not or only minimally changed by innocuous mechanical stimuli (flexion of and innocuous pressure to the knee in the cat and innocuous pressure to the knee of the rat) but was significantly altered by electrical stimulation of the tibial nerve in the cat (sufficient to excite unmyelinated afferent fibres), indicating release of the peptide by the latter stimulus. During the first hours of the development of an experimental inflammation in the knee joint induced by intra-articular injections of kaolin and carrageenan, the pattern of binding of [125I]calcitonin gene-related peptide changed. In the cat, the level of immunoreactive calcitonin gene-related peptide showed a persistent increase in the gray matter and up to the surface of the cord and release was slightly increased by innocuous stimuli. In the rat, increased levels of immunoreactive calcitonin gene-related peptide were mainly seen in the superficial and deep dorsal horn during innocuous pressure (this stimulus did not evoke release of the peptide prior to inflammation) and noxious pressure applied to the injected knee, whereas increased basal levels were only observed at later stages. These data show that the development of an acute experimental inflammation in the joint is associated with an enhancement of the intraspinal release of immunoreactive calcitonin gene-related peptide. Since the changes in the release were noted at an early stage, within the first hours, they could contribute to the generation of inflammation-evoked changes of the responsiveness of spinal cord neurons and hence to the mechanisms inducing inflammatory pain.

The morphology and innervation of facial vibrissae in the tammar wallaby, Macropus eugenii.

PubMed Central

Marotte, L R; Rice, F L; Waite, P M

1992-01-01

The morphology of the vibrissal follicles on the mystacial pad of the tammar wallaby is similar to that seen in other species except that the follicles lack a ringwulst or ring sinus. Instead, the mesenchymal sheath is thickened around the central region of the hair shaft. The follicle is innervated by both deep and superficial vibrissal nerves. The deep nerve enters as 4-11 fascicles which can be in close proximity or widely distributed around the hair. C1 follicles received more myelinated nerve fibres (252 +/- 31) than the smaller C4 follicles (174 +/- 43). The deep vibrissal nerve supplies the thickened mesenchymal sheath, the narrow 'waist' region above and the majority of endings in the inner conical body (ICB), while the superficial nerves provide a sparse innervation to the ICB and rete ridge. Receptors present in the follicle were of 4 types: (1) Merkel cells, especially numerous in the outer root sheath of the 'waist' region and occasionally in the ICB and rete ridge; (2) and (3) lanceolate and lamellated endings parallel to the hair shaft in both the mesenchymal thickening and the 'waist' region where they were particularly dense; (4) free nerve endings in the mesenchymal thickening, 'waist' region and ICB. No corpuscular, bulbous or Ruffini endings were seen. The innervation of the intervibrissal fur was similar to that described in other species. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:1487434

Release of substance P from the cat spinal cord.

PubMed Central

Go, V L; Yaksh, T L

1987-01-01

1. The present experiments examine the physiology and pharmacology of the release of substance P-like immunoreactivity (SP-l.i.), from the spinal cord in the halothane-anaesthetized, artificially ventilated cat. 2. Resting release of SP-l.i. was 36 +/- 4 fmol/30 min (mean +/- S.E.; n = 106). Bilateral stimulation of the sciatic nerves at intensities which evoked activity in fibres conducting at A beta conduction velocities (greater than 40 m/s), resulted in no change in blood pressure, pupil diameter or release of SP-l.i. Stimulation intensities which activate fibres conducting at velocities less than 2 m/s resulted in increased blood pressure, miosis and elevated release of SP-l.i. (278 +/- 16% of control). 3. The relationship between nerve-stimulation frequency and release was monotonic up to approximately 20 Hz. Higher stimulation frequencies did not increase the amounts of SP-l.i. released. At 200 Hz there was a reduction. 4. Capsaicin (0.1 mM) increased the release of SP-l.i. from the spinal cord and resulted in an acute desensitization to subsequent nerve stimulation. This acute effect was not accompanied by a reduction in spinal levels of SP-l.i. measured 2 h after stimulation. 5. Cold block of the cervical spinal cord resulted in an increase in the amounts of SP-l.i. released by nerve stimulation. 6. Pre-treatment with intrathecal 5,6-dihydroxytryptamine (300 micrograms) 7 days prior to the experiment caused a reduction in the dorsal and ventral horn stores of SP-l.i., but had no effect on the release of SP-l.i. evoked by nerve stimulation. Similar pre-treatment with intrathecal capsaicin (300 micrograms) resulted in depletion of SP-l.i. in the dorsal but not in the ventral horn of the spinal cord and diminished the release of SP-l.i. evoked by nerve stimulation. 7. Intense thermal stimulation of the flank resulted in small (20-35%), but reliable increases in the release of SP-l.i. above control. 8. Putative agonists for the opioid mu-receptor (morphine, 10-100 microM; sufentanil, 1 microM), and for the delta-receptor (D-Ala2-D-Leu5-enkephalin, 1-10 microM; D-Pen2-D-Pen5-enkephalin, 10 microM), but not the kappa-receptor (U50488H, 100-1000 microM), produced a dose-dependent, naloxone-reversible reduction of the evoked, but not of the resting release of SP-l.i. (-)-Naloxone, but not (+)-naloxone, resulted in a significant increase in evoked but not resting SP-l.i. release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2451003

Effect of sensory denervation on the structure and physiologic responsiveness of rabbit lacrimal gland.

PubMed

Meneray, M A; Bennett, D J; Nguyen, D H; Beuerman, R W

1998-01-01

This work was conducted to determine the effects of unilateral trigeminal ganglion ablation on lacrimal gland structure and secretory activity. Adult male New Zealand rabbits underwent unilateral thermocoagulation of the ophthalmic division of the trigeminal ganglion. Sensory denervation was affirmed by anatomic inspection of the lesion and transmission electron microscopy (TEM) of the lacrimal gland innervation. Eight to 10 days after the procedure, the intraorbital lacrimal glands were removed from both sides. To compare the physiologic competence of the intact and denervated glands, freshly isolated gland fragments from the paired intact and denervated glands were stimulated with carbachol (100 microM), isoproterenol (10 microM), phorbol-12,13-dibutyrate (PDBu, 10 microM), forskolin (40 microM), or vehicle. Total secreted protein was measured at 30 or 60 min after the establishment of baseline values. Intact and denervated glands also were examined by light and TEM, and the morphologic appearance of the acinar structures as well as the appearance of nerves innervating the gland after denervation were assessed. Similar experiments were conducted with animals that underwent unilateral superior cervical ganglionectomy. Tissues from sensory denervated glands released significantly more protein than did tissues from innervated glands in response to in vitro stimulation by carbachol or isoproterenol but not in response to PDBu or forskolin. Microscopy showed that the acinar cells that had undergone sensory denervation showed a massive accumulation of secretory granules. The secretory granules filled the entire cytoplasmic space and displaced the ellipsoidal nuclei to the extreme periphery. Examination of segments of nerves revealed numerous unmyelinated axons, a few small-diameter myelinated axons, and a large amount of nerve degeneration after sensory denervation. In contrast to the effects of sensory denervation, sympathetic denervation did not alter either the acinar appearance or secretory responsiveness of the gland. Loss of the considerable sensory innervation from the trigeminal ganglion has pronounced effects on the pharmacologic responsiveness and the structure of the lacrimal gland. The effects of sensory innervation on the gland may be mediated through two possible pathways: direct input to the gland or control of the preganglionic parasympathetic pathway.

Isometric contractions of motor units in a fast twitch muscle of the cat

PubMed Central

Bagust, J.; Knott, Sarah; Lewis, D. M.; Luck, J. C.; Westerman, R. A.

1973-01-01

1. Isosmetric contractions of cat flexor digitorum longus whole muscles and of functionally isolated motor units have been measured under conditions similar to those used by Buller & Lewis (1965a). 2. Motor unit twitch time to peak was inversely related to axonal conduction velocity. The logarithm of tetanic tension was directly related to conduction velocity. These relationships suggest that each motoneurone has an influence on the muscle fibres which it innervates. 3. The ratio of twitch to tetanic tension was directly related to the time to peak of the motor unit. This fact might be explained by variation between motor units of the duration of `active state'. 4. The muscle length at which tension was maximal varied between motor units and the optima were found over the range of muscle lengths which could occur in the body. Slow motor units had longer optimal lengths. 5. The sample of motor units was considered to be unbiased because the distribution of axon conduction velocities was compatible with reported motor fibre diameter spectra of the muscle nerve. The mean motor unit tetanic tension gave a reasonable estimate of the number of α-motor axons in the muscle nerve. Twitch tensions gave a value that was 40% higher. 6. Motor unit and whole muscle data were in good agreement for length-tetanus tension curves, for times to peak and for twitch-tetanus ratios at long muscle lengths. PMID:4715372

Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

PubMed

La Cesa, S; Di Stefano, G; Leone, C; Pepe, A; Galosi, E; Alu, F; Fasolino, A; Cruccu, G; Valeriani, M; Truini, A

2018-01-01

In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system. © 2017 European Pain Federation - EFIC®.

The role of colonic mast cells and myenteric plexitis in patients with diverticular disease.

PubMed

Bassotti, Gabrio; Villanacci, Vincenzo; Nascimbeni, Riccardo; Antonelli, Elisabetta; Cadei, Moris; Manenti, Stefania; Lorenzi, Luisa; Titi, Amin; Salerni, Bruno

2013-02-01

Gut mast cells represent an important cell population involved in intestinal homeostasis and inflammatory processes. However, their possible role has not to date been investigated in colonic diverticular disease. This study aims to evaluate colonic mast cells in patients undergoing surgery for diverticular disease. Surgical resection samples from 27 patients undergoing surgery for diverticular disease (12 emergency procedures for severe disease and 15 elective procedures) were evaluated. The number of mast cells was assessed in the various layers by means of a specific antibody (tryptase) and compared with those evaluated in ten controls. In patients with mast cells degranulation, double immunohistochemistry, also assessing nerve fibres, was carried out. In addition, the presence of myenteric plexitis was sought. Compared with controls, the number of mast cells in diverticular patients was significantly increased, both as an overall figure and in the various layers of the large bowel. In patients in whom mast cells degranulation was present, these were always closed to nerve fibres. No differences were found between the two subgroups of patients with respect to the number and distribution of mast cells; however, all patients undergoing emergency surgery (but none of those undergoing elective procedures) had myenteric plexitis, represented by lymphocytic infiltration in 67 % and eosinophilic infiltration in 33 % of cases. Patients with diverticular disease display an increase of mast cells in the large bowel. The presence of myenteric plexitis in those with complicated, severe disease, suggest that this could represent a histopathologic marker of more aggressive disease.

Recovery of function, peripheral sensitization and sensory neurone activation by novel pathways following axonal injury in Aplysia californica.

PubMed

Dulin, M F; Steffensen, I; Morris, C E; Walters, E T

1995-10-01

Recovery of behavioural and sensory function was examined following unilateral pedal nerve crush in Aplysia californica. Nerve crush that transected all axons connecting the tail to the central nervous system (CNS) eliminated the ipsilateral tail-evoked siphon reflex, whose sensory input travels in the crushed tail nerve (p9). The first reliable signs of recovery of this reflex were observed within 1 week, and most animals displayed tail-evoked siphon responses within 2 weeks. Wide-dynamic-range mechanosensory neurons with somata in the ventrocaudal (VC) cluster of the ipsilateral pleural ganglion exhibited a few receptive fields (RFs) on the tail 3 weeks after unilateral pedal nerve crush, indicating that the RFs had either regenerated or been reconnected to the central somata. These RFs were smaller and sensitized compared with corresponding RFs on the contralateral, uncrushed side. Centrally conducted axon responses of VC sensory neurones to electrical stimulation distal to the nerve crush site did not reappear until at least 10 days after the crush. Because the crush site was much closer to the CNS than to the tail, the failure of axon responses to be restored earlier than the behavioural responses indicates that early stages of reflex recovery are not due to regeneration of VC sensory neurone axons into the tail. Following nerve crush, VC sensory neurones often could be activated by stimulating central connectives or peripheral nerves that do not normally contain the sensory neurone's axons. These results suggest that recovery of behavioral function after nerve injury involves complex mechanisms, including regenerative growth of axotomized VC sensory neurones, sensitization of regenerating RFs and sprouting of VC sensory neurone fibres within the CNS. Furthermore, the rapidity of behavioural recovery indicates that its initial phases are mediated by additional mechanisms, perhaps centripetal regeneration of unidentified sensory neurones having peripheral somata, or transient reconnection of proximal and distal stumps of axotomized VC cells.

Electron Microscopic Observations of the Carotid Body of the Cat

PubMed Central

Ross, Leonard L.

1959-01-01

Carotid bodies were removed from cats, fixed in buffered 1 per cent osmic acid, embedded in deaerated, nitrogenated methacrylate, and cut into thin sections for electron microscopic study. The carotid body is seen to be composed of islands of chemoreceptor and sustentacular cells surrounded by wide irregular sinusoids. These cells are separated from the sinusoids by relatively broad interstitial spaces which are filled with collagen, fibroblasts, and many unmyelinated nerve fibers with their Schwann cell sheaths. The chemoreceptor cells are surrounded by the flattened, multiprocessed sustentacular cells which serve to convey the axons from an interstitial to a pericellular location. These sustentacular cells are assumed to be lemmoblastic in origin. Relatively few axons are seen to abut on the chemoreceptor cells. The cytoplasm of the chemoreceptor cell is characterized by numerous small mitochondria, units of granular endoplasmic reticulum, a small Golgi complex, and a variety of vesicles. There are many small vesicles diffusely scattered throughout the cytoplasm. In addition, there is a small number of dark-cored vesicles of the type which has been previously described in the adrenal medulla. These are usually associated with the Golgi complex. These findings are discussed in relation to the concepts of the origin of the chemoreceptor cell and the nature of the synapse. PMID:14439171

Neuroprotective vaccination with copolymer-1 decreases laser-induced retinal damage

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Rosner, Mordechai

2003-06-01

The retinal damage induced by laser photocoagulation increases manifold by the secondary degeneration process whereby tissues adjacent to the primary lesion are destroyed. The neuroprotective effect of immunization by glatiramer acetate (Copolymer-1, Cop-1) in adjuvant was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions. The present study tested the neuroprotective ability of Cop-1 to reduce the spread of laser-induced retinal damage. Standard argon laser lesions were created in 72 DA pigmented rats divided into four groups: two Cop-1 treated groups (animals treated seven days before or immediately after the laser session) and two control groups treated respectively by saline or the effective but toxic neuroprotective compound MK-801. The histological and morphological evaluations of the lesions 3, 20, and 60 days after the injury revealed significant reduction in photoreceptor loss of the retinas of the pre-immunized animals. Cop-1 given after the laser injury did not prevent cell loss significantly, while the neuroprotective effect of MK-801 was observed only on the third day after the laser injury. The results show that pre-immunization with Cop-1 is neuroprotective in unmyelinated (gray matter) neural tissue such as the retina. This approach may be of clinical significance in ameliorating laser-induced retinal injuries in humans.

Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis.

PubMed Central

Boutin, B; Routon, M C; Rocchiccioli, F; Mayer, M; Leverger, G; Robain, O; Ponsot, G; Arthuis, M

1988-01-01

A 12 year old patient who developed clinical, biochemical and histological features of erythrophagocytic lymphohistiocytosis is described. In contrast to previously reported cases, the prominent neurological feature was a subacute sensorimotor polyneuropathy. Sural nerve biopsy showed a marked reduction of myelinated fibres and severe axonal lesions, absence of histiocyte infiltration and deposits of IgM along the epineurium. In addition to the hypertriglyceridaemia previously described in this condition, an elevation of plasma very long-chain fatty acids and phytanic acid was found which suggests a transient impairment of peroxisomal functions. Images PMID:3346698

Aspects of dentinal and pulpal pain. Pain of dentinal and pulpal origin--a review for the clinician.

PubMed

Figdor, D

1994-04-01

Recent advances in understanding the mechanisms of pain arising from the dental pulp serve to benefit patients by improving the clinician's ability to diagnose and treat pain. There are two types of pain arising from the pulp which are mediated by entirely different nerve fibres, each with their own individual characteristics. One is a short, sharp fast pain which is induced by stimuli which cause a rapid fluid flow within the dentinal tubules. Such stimuli include cold, heat, air, drilling, and osmotic stimuli. Once the affected teeth are identified, they can often be treated by sealing the open, exposed dentine. The second type of pain is experienced as a slow, dull, aching, poorly localized pain which is mediated by pain fibres activated by stimuli which are noxious to the pulp, such as prolonged damaging heat and inflammatory mediators. Pain of this character can be difficult to diagnose and often indicates serious pulp damage necessitating removal of the offending pulp by endodontic therapy.

Posterior Branches of Lumbar Spinal Nerves - Part I: Anatomy and Functional Importance.

PubMed

Kozera, Katarzyna; Ciszek, Bogdan

2016-01-01

The aim of this paper is to compare anatomic descriptions of posterior branches of the lumbar spinal nerves and, on this basis, present the location of these structures. The majority of anatomy textbooks do not describe these nerves in detail, which may be attributable to the fact that for many years they were regarded as structures of minor clinical importance. The state of knowledge on these nerves has changed within the last 30 years. Attention has been turned to their function and importance for both diagnostic practice and therapy of lower back pain. Summarising the available literature, we may conclude that the medial and lateral branches separate at the junction of the facet joint and the distal upper edge of the transverse process; that the size, course and area supplied differ between the lateral and the medial branch; and that facet joints receive multisegmental innervation. It has been demonstrated that medial branches are smaller than the respective lateral branches and they have a more constant course. Medial branches supply the area from the midline to the facet joint line, while lateral branches innervate tissues lateral to the facet joint. The literature indicates difficulties with determining specific anatomic landmarks relative to which the lateral branch and the distal medial branch can be precisely located. Irritation of sensory fibres within posterior branches of the lumbar spinal nerves may be caused by pathology of facet joints, deformity of the spine or abnormalities due to overloading or injury. The anatomic location and course of posterior branches of spinal nerves should be borne in mind to prevent damaging them during low-invasive analgesic procedures.

Physiological and pathological characterization of capsaicin-induced reversible nerve degeneration and hyperalgesia.

PubMed

Chiang, H; Chang, K-C; Kan, H-W; Wu, S-W; Tseng, M-T; Hsueh, H-W; Lin, Y-H; Chao, C-C; Hsieh, S-T

2018-07-01

The study aimed to investigate the physiology, psychophysics, pathology and their relationship in reversible nociceptive nerve degeneration, and the physiology of acute hyperalgesia. We enrolled 15 normal subjects to investigate intraepidermal nerve fibre (IENF) density, contact heat-evoked potential (CHEP) and thermal thresholds during the capsaicin-induced skin nerve degeneration-regeneration; and CHEP and thermal thresholds at capsaicin-induced acute hyperalgesia. After 2-week capsaicin treatment, IENF density of skin was markedly reduced with reduced amplitude and prolonged latency of CHEP, and increased warm and heat pain thresholds. The time courses of skin nerve regeneration and reversal of physiology and psychophysics were different: IENF density was still lower at 10 weeks after capsaicin treatment than that at baseline, whereas CHEP amplitude and warm threshold became normalized within 3 weeks after capsaicin treatment. Although CHEP amplitude and IENF density were best correlated in a multiple linear regression model, a one-phase exponential association model showed better fit than a simple linear one, that is in the regeneration phase, the slope of the regression line between CHEP amplitude and IENF density was steeper in the subgroup with lower IENF densities than in the one with higher IENF densities. During capsaicin-induced hyperalgesia, recordable rate of CHEP to 43 °C heat stimulation was higher with enhanced CHEP amplitude and pain perception compared to baseline. There were differential restoration of IENF density, CHEP and thermal thresholds, and changed CHEP-IENF relationships during skin reinnervation. CHEP can be a physiological signature of acute hyperalgesia. These observations suggested the relationship between nociceptive nerve terminals and brain responses to thermal stimuli changed during different degree of skin denervation, and CHEP to low-intensity heat stimulus can reflect the physiology of hyperalgesia. © 2018 European Pain Federation - EFIC®.

Presynaptic Proteins as Markers of the Neurotoxic Activity of BmjeTX-I and BmjeTX-II Toxins from Bothrops marajoensis (Marajó Lancehead) Snake Venom.

PubMed

Lisboa, Antonio; Melaré, Rodolfo; Franco, Junia R B; Bis, Carolina V; Gracia, Marta; Ponce-Soto, Luis A; Marangoni, Sérgio; Rodrigues-Simioni, Léa; da Cruz-Höfling, Maria Alice; Rocha, Thalita

2016-01-01

Neuromuscular preparations exposed to B. marajoensis venom show increases in the frequency of miniature end-plate potentials and twitch tension facilitation followed by presynaptic neuromuscular paralysis, without evidences of muscle damage. Considering that presynaptic toxins interfere into the machinery involved in neurotransmitter release (synaptophysin, synaptobrevin, and SNAP25 proteins), the main objective of this communication is to analyze, by immunofluorescence and western blotting, the expression of the synaptic proteins, synaptophysin, synaptobrevin, and SNAP25 and by myography, light, and transmission electron microscopy the pathology of motor nerve terminals and skeletal muscle fibres of chick biventer cervicis preparations (CBC) exposed in vitro to BmjeTX-I and BmjeTX-II toxins from B. marajoensis venom. CBC incubated with toxins showed irreversible twitch tension blockade and unaffected KCl- and ACh-evoked contractures, and the positive colabelling of acetylcholine receptors confirmed that their action was primarily at the motor nerve terminal. Hypercontraction and loose myofilaments and synaptic vesicle depletion and motor nerve damage indicated that the toxins displayed both myotoxic and neurotoxic effect. The blockade resulted from interference on synaptophysin, synaptobrevin, and SNAP25 proteins leading to the conclusion that BmjeTX-I and BmjeTX-II affected neurotransmitter release machinery by preventing the docking of synaptic vesicles to the axolemma of the nerve terminal.

Nerve fibre layer analysis with GDx with a variable corneal compensator in patients with multiple sclerosis.

PubMed

Della Mea, Giovanni; Bacchetti, Sonia; Zeppieri, Marco; Brusini, Paolo; Cutuli, Daniela; Gigli, Gian Luigi

2007-01-01

To evaluate the ability of GDx with variable corneal compensator (VCC) compared to visual-evoked potentials (VEPs) and standard automated perimetry (SAP) in the detection of early optic nerve damage in patients with multiple sclerosis (MS). 46 eyes of 23 MS patients were included. Ten of them had a history of acute retrobulbar optic neuritis. A control group of 20 normal subjects was also included. All subjects underwent a complete ophthalmological examination and testing with SAP, GDx VCC and VEPs. 19 eyes (41.3%) were abnormal with GDx VCC compared to 38 eyes (82.6%) with SAP and 31 (64.4%) with VEPs. In the optic neuritis group, 9 eyes (69.2%) had optic nerve pallor; SAP was abnormal in 8 of these eyes (61.5%) while VEPs and GDx VCC were abnormal in 6 eyes (46.1%). 2/20 eyes (10.0%) in the control group gave a false-positive abnormal result with SAP. GDx VCC and VEP were normal for all the eyes in the control group. GDx VCC is less able to detect early defects in MS patients compared to the currently used standard techniques of SAP and VEPs. Copyright (c) 2007 S. Karger AG, Basel.

Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

PubMed Central

Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

1988-01-01

1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the effect appeared to require the participation of excitatory amino acids because it was blocked by APV and by kynurenate. 6. The finding that tetrodotoxin substantially reduced the ability of excitatory amino acid agonists and tachykinins to elevate [K+]o suggests that discharges in interneurones as a result of excitatory amino acid receptor activation are responsible for the postsynaptic component of delta[K+]o. PMID:3261795

Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

PubMed

Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

1988-03-01

1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the effect appeared to require the participation of excitatory amino acids because it was blocked by APV and by kynurenate. 6. The finding that tetrodotoxin substantially reduced the ability of excitatory amino acid agonists and tachykinins to elevate [K+]o suggests that discharges in interneurones as a result of excitatory amino acid receptor activation are responsible for the postsynaptic component of delta[K+]o.

Plasticity of the transverse tubules following denervation and subsequent reinnervation in rat slow and fast muscle fibres.

PubMed

Takekura, Hiroaki; Tamaki, Hiroyuki; Nishizawa, Tomie; Kasuga, Norikatsu

2003-01-01

We have studied the effects of short term denervation followed by reinnervation on the ultrastructure of the membrane systems and on the content of and distribution of key proteins involved in calcium regulation of fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus (SOL) muscle fibres. Ischiadic nerve freezing resulted in total lack of neuromuscular transmission for 3 days followed by a slow recovery, but no decline in twitch force elicited by direct stimulation. The latter measurements indicate no significant atrophy within this time frame. The membrane systems of skeletal muscle fibres were visualized using Ca92+)-K3Fe(CN)6-OsO4 techniques and observed using a high voltage electron microscope. [3H]nitrendipine binding was used to detect levels of dihydropyridine receptor (DHPR) expression. The Ca2+ pumping free sarcoplasmic reticulum domains were not affected by the denervation, but the Ca2+ release domains were dramatically increased, particularly in the FT-EDL muscle fibres. The increase is evidenced by a doubling up of the areas of contacts between SR and transverse (t-) tubules, so that in place of the normal triadic arrangement, pentadic and heptadic junctions, formed by multiple interacting layers of ST and t-tubules are seen. Frequency of pentads and heptads increases and declines in parallel to the denervation and reinnervation but with a delay. Immunofluorecence and electron microscopy observations show presence of DHPR and ryanodine receptor clusters at pentads and heptads junctions. A significant (P < 0.01) positive correlation between the level of [3H]nitrendipine binding component and the frequency pentads and heptads was observed in both the FT-EDL and ST-SOL muscle fibres indicating that overexpression of DHPRs accompanies the build up extra junctional contacts. The results indicate that denervation reversibly affects the domains of the membrane systems involved in excitation-contraction coupling.

Psychophysical Investigations into the Role of Low-Threshold C Fibres in Non-Painful Affective Processing and Pain Modulation.

PubMed

Shaikh, Sumaiya; Nagi, Saad S; McGlone, Francis; Mahns, David A

2015-01-01

We recently showed that C low-threshold mechanoreceptors (CLTMRs) contribute to touch-evoked pain (allodynia) during experimental muscle pain. Conversely, in absence of ongoing pain, the activation of CLTMRs has been shown to correlate with a diffuse sensation of pleasant touch. In this study, we evaluated (1) the primary afferent fibre types contributing to positive (pleasant) and negative (unpleasant) affective touch and (2) the effects of tactile stimuli on tonic muscle pain by varying affective attributes and frequency parameters. Psychophysical observations were made in 10 healthy participants. Two types of test stimuli were applied: stroking stimulus using velvet or sandpaper at speeds of 0.1, 1.0 and 10.0 cm/s; focal vibrotactile stimulus at low (20 Hz) or high (200 Hz) frequency. These stimuli were applied in the normal condition (i.e. no experimental pain) and following the induction of muscle pain by infusing hypertonic saline (5%) into the tibialis anterior muscle. These observations were repeated following the conduction block of myelinated fibres by compression of sciatic nerve. In absence of muscle pain, all participants reliably linked velvet-stroking to pleasantness and sandpaper-stroking to unpleasantness (no pain). Likewise, low-frequency vibration was linked to pleasantness and high-frequency vibration to unpleasantness. During muscle pain, the application of previously pleasant stimuli resulted in overall pain relief, whereas the application of previously unpleasant stimuli resulted in overall pain intensification. These effects were significant, reproducible and persisted following the blockade of myelinated fibres. Taken together, these findings suggest the role of low-threshold C fibres in affective and pain processing. Furthermore, these observations suggest that temporal coding need not be limited to discriminative aspects of tactile processing, but may contribute to affective attributes, which in turn predispose individual responses towards excitatory or inhibitory modulation of pain.

Pain in chemotherapy-induced neuropathy--more than neuropathic?

PubMed

Geber, Christian; Breimhorst, Markus; Burbach, Berenike; Egenolf, Christina; Baier, Bernhard; Fechir, Marcel; Koerber, Juergen; Treede, Rolf-Detlef; Vogt, Thomas; Birklein, Frank

2013-12-01

Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre neuropathies were more frequent than small-fibre neuropathy (1.4%). The 5 major chemotherapeutic regimens impacted differently on large- but not on small-fibre function and did not predict painfulness. Chronic pain associated with CIN was reported in 41.7%. Painless and painful CIN did not differ in QST profiles or electrophysiological findings, but different somatosensory patterns were found in CIN subgroups (pain at rest [RestP], n = 25; movement-associated pain [MovP], n = 15; both pain characteristics [MovP+RestP], n = 21; or no pain [NonP], n = 85): small-fibre function (cold-detection threshold, CDT: z score: -1.46 ± 0.21, P < 0.01) was most impaired in RestP; mechanical hyperalgesia was exclusively found in MovP (z score: +0.81 ± 0.30, P < 0.05). "Anxiety" discriminated between painful and painless CIN; "CDT" and "anxiety" discriminated between patients with ongoing (RestP) and movement-associated pain (MovP) or pain components (MovP+RestP). The detrimental effect of chemotherapy on large fibres failed to differentiate painful from painless CIN. Patients stratified for musculoskeletal or neuropathic pain, however, differed in psychological and somatosensory parameters. This stratification might allow for the application of a more specific therapy. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson's disease.

PubMed

Stemplewitz, Birthe; Keserü, Matthias; Bittersohl, Diana; Buhmann, Carsten; Skevas, Christos; Richard, Gisbert; Hassenstein, Andrea

2015-12-01

Whether retinal degeneration is part of the degenerative processes in patients with Parkinson's disease (PD) is still unclear. This cross-sectional study was undertaken to compare the retinal morphology of patients with PD and healthy controls using spectral domain optical coherence tomography (SD-OCT) and scanning laser polarimetry (SLP). Both eyes of patients with PD (n = 108) and healthy controls (n = 165) were examined using SD-OCT and SLP on the same day. Data on the thickness of the retinal nerve fibre layer (RNFL) of all quadrants and the macular area were acquired by OCT (Cirrus, Zeiss). The SLP device (Glaucoma diagnostics (GDx), Zeiss) measured the RNFL and calculated the nerve fibre index (NFI). All patients and probands were checked for concomitant ocular disorders by an ophthalmologist. Visual acuity, intraocular pressure (IOP), objective refraction and the anterior and posterior segment were assessed. Patients with PD showed a reduced macular volume and a reduced central subfield thickness in OCT examinations. The RNFL in the different quadrants did not differ significantly from that of controls. SLP data showed a reduced average RNFL thickness, a decreased thickness of the inferior quadrant and an increase of the NFI in patients with PD. PD may be associated with reduced thickness and volume of the macula and a reduced thickness of the RNFL in the inferior quadrant of the retina. Investigations using SD-OCT and SLP revealed distinct but significant differences between patients with PD and healthy controls. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Evidence for CGRP re-uptake in rat dura mater encephali

PubMed Central

Gupta, Saurabh; Amrutkar, Dipak Vasantrao; Mataji, Aydin; Salmasi, Hassan; Hay-Schmidt, Anders; Sheykhzade, Majid; Messlinger, Karl; Olesen, Jes; Jansen-Olesen, Inger

2010-01-01

BACKGROUND AND PURPOSE Calcitonin gene-related peptide (CGRP) is widely distributed in the trigeminovascular system and released from sensory fibres of the cranial dura mater upon noxious stimulation. Such release may be a mechanism underlying migraine headache. Based on data from guinea pig basilar artery preparations, we have here studied CGRP release and uptake in an organ preparation of the hemisected rat skull. EXPERIMENTAL APPROACH CGRP release from the cranial dura was quantified by a commercial enzyme-linked immunoassay. CGRP was depleted using repetitive challenges of capsaicin. After incubating the tissue with CGRP for 20 min and extensive washing, another capsaicin challenge was performed. Immunohistochemistry was used to visualize CGRP immunofluorescence in dural nerve fibres. KEY RESULTS Capsaicin-induced CGRP release was attenuated by the transient receptor potential vanilloid receptor type I antagonist capsazepine or by Ca2+-free solutions. After the CGRP-depleted preparation had been exposed to exogenous CGRP, capsaicin-induced CGRP release was increased compared to the challenge just prior to incubation. CGRP uptake was not influenced by Ca2+-free solutions. Olcegepant and CGRP8–37 (CGRP receptor antagonists) did not affect uptake of CGRP. However, a monoclonal CGRP-binding antibody decreased CGRP uptake significantly. Release of CGRP after incubation was attenuated by Ca2+-free solutions and by capsazepine. Immunohistochemical assays indicated a weak trend towards CGRP uptake in rat dura mater. CONCLUSION AND IMPLICATIONS We have presented evidence for CGRP uptake in nerves and its re-release in rat dura mater. This may have implications for the pathophysiology and treatment of migraine. PMID:20804493

Morphological patterns in children with ganglion related enteric neuronal abnormalities.

PubMed

Henna, Nausheen; Nagi, Abdul H; Sheikh, Muhammad A; Shaukat, Mahmood

2011-01-01

Hirschsprung's Disease (HD) is a developmental disorder of enteric nervous system characterised by the absence of ganglion cells in submucosal (Meissner's) and myenteric (Aurbach's) plexuses of distal bowel. The purpose of the present study was to observe and report the morphological patterns of ganglion related enteric neuronal abnormalities in children presented with clinical features of (HD) in a Pakistani population. A total of 92 patients with clinical presentation of HD were enrolled between March 2009 and October 2009. Among them, 8 were excluded according to the exclusion criteria. After detailed history and physical examination, paraffin embedded H and E stained sections were prepared from the serial open biopsies from colorectum. The data was analysed using SPSS-17. Frequencies and percentages are given for qualitative variables. Non-parametric Binomial Chi-Square test was applied to observe within group associations and p<0.05 was considered statistically significant. Among 84 patients, 13 (15.5%) proved to be normally ganglionic whereas 71 (84.5%) showed ganglion related enteric neuronal abnormalities namely isolated hypoganglionosis 9 (12.7%), immaturity of ganglion cells 9 (12.7%), isolated hyperganglionosis (IND Type B) 2 (2.8%) and Hirschsprung's disease 51 (71.8%). Among HD group, 34 (66.7%) belonged to isolated form and 17 (33.3%) showed combined ganglion related abnormalities. Hirschsprung's disease is common in Pakistani population, followed by hypoganglionosis, immaturity of ganglion cells and IND type B. The presence of hypertrophic nerve fibres was significant in HD, hyperganglionosis and hypoganglionosis, whereas, no hypertrophic nerve fibres were appreciated in immaturity of ganglion cell group.

Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies.

PubMed

Koike, Haruki; Kadoya, Masato; Kaida, Ken-Ichi; Ikeda, Shohei; Kawagashira, Yuichi; Iijima, Masahiro; Kato, Daisuke; Ogata, Hidenori; Yamasaki, Ryo; Matsukawa, Noriyuki; Kira, Jun-Ichi; Katsuno, Masahisa; Sobue, Gen

2017-06-01

To investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes. We assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings. Characteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo-glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p<0.05). Paranodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo-glial junctional molecules. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

CO2 laser nerve stimulator with flat-top irradiance profile for human pain research

NASA Astrophysics Data System (ADS)

McCaughey, Ryan Gerard

Human pain research aims to further the understanding of how pain is processed by the body. Studies require a reproducible, quantifiable, scalable, pain specific and safe stimulus. Using laser light to raise the temperature of the skin to painful levels is a good method of satisfying these conditions. The CO[2] laser is an ideal source because its infrared radiation is readily absorbed in the upper layers of the skin, where the free nerve endings of pain-conveying fibres are located, causing localised heating and evoking pain. A pain stimulator based on a CO[2] laser has been developed. It is computer controlled with a graphical interface so that non specialists can easily operate the laser. Safety features have been incorporated to protect the operator and the subject. These include activation of a shutter to block the beam and shut-down of the laser, when, for example, potentially harmful laser parameters are selected or abnormal signals are sent to the laser. The CO[2] laser normally operates in TEM[00] mode, i.e. the irradiance of the beam decreases roughly exponentially from the centre. This is not ideal for thermal stimulation, since it will generate a temperature that also has a peak in the centre of the beam. This will result in non-uniform activation of nerve fibres. Lenses have been developed to redistribute the energy of the beam to produce a flattened super Gaussian irradiance profile for uniform heating of the skin. The shape of the lenses was determined by geometrical optics. They work by refracting the more intense central part of the beam towards the periphery. Solution of the heat transfer equation by a finite differences method, confirmed that the super Gaussian profile generated by the bean shaper produces a more uniform temperature distribution in skin. The model was also used to predict how varying skin parameters, such as thickness and water content, affects the temperature generated by irradiation with a CO[2] laser beam. The predicted skin temperatures matched the temperatures measured during thermal stimulation with the laser. The risk of damaging the tissue was also calculated from the modelled temperature distribution. Psychophysical techniques were used to characterise the laser stimulator compared to an existing laser stimulator. Differences in the temporal provides of the lasers resulted in different pain sensations for beams of the same energy. The conduction velocities of thermally stimulated fibres were estimated by recording the reaction time to laser irradiation. It was found that the super Gaussian beam evokes pain at a lower temperature than a TEM[00] beam. It is, therefore, a safer source for evoking pain in human pain studies.

[Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

PubMed

Indo, Yasuhiro

2015-05-01

Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

Vibration-induced multifocal neuropathy in forestry workers: electrophysiological findings in relation to vibration exposure and finger circulation.

PubMed

Bovenzi, M; Giannini, F; Rossi, S

2000-11-01

To investigate neural conduction in the upper limbs of symptomatic forestry workers with and without exposure to hand-transmitted vibration. A further aim was to assess the possible relationships between vibration exposure, nerve conduction and finger circulation in the forestry workers who used chain saws. A detailed neurophysiological investigation was performed on the upper extremities of 20 chain saw workers, 20 forestry operators with heavy manual work but without vibration exposure, and 20 healthy male controls. All subjects were screened to exclude polyneuropathy. Measurements of sensory and motor nerve conduction (velocity and amplitude) were obtained bilaterally from the median, ulnar and radial nerves. To assess peripheral vascular function, the forestry workers underwent a cold test with plethysmographic measurement of finger systolic blood pressure (FSBP). In the chain saw operators, vibration exposure was evaluated according to the International Standard ISO 5349. Indices of daily vibration exposure and lifetime cumulative vibration dose were estimated for each chain saw operator. Sensory nerve conduction in several segments of the median and radial nerves was significantly reduced in the chain saw operators compared with that in the workers doing heavy manual work and the controls. The neurophysiological pattern more frequently observed in the chain saw operators was a multifocal nerve conduction impairment to several neural segments with predominant involvement of sensory rather than motor fibres. Sensory nerve conduction velocities in the hands of the chain saw operators were inversely related to both daily and lifetime cumulative vibration exposures. In the vibration-exposed forestry workers, neither were sensori-motor complaints associated with vascular symptoms (finger whiteness) nor were electrophysiological data related to cold-induced changes in FSBP. Exposure to hand-transmitted vibration, in addition to ergonomic stress factors, can contribute to peripheral nerve disorders occurring in forestry workers who operate chain saws. The findings of this study suggest the existence of an exposure-effect relationship for vibration-induced neuropathy. Different underlying mechanisms are likely to be involved in the pathogenesis of the neurological and vascular components of the hand-arm vibration syndrome.

The effect of rehabilitation exercises combined with direct vagina low voltage low frequency electric stimulation on pelvic nerve electrophysiology and tissue function in primiparous women: A randomised controlled trial.

PubMed

Yang, Sumian; Sang, Wenshu; Feng, Jing; Zhao, Haifeng; Li, Xian; Li, Ping; Fan, Hongfang; Tang, Zengjun; Gao, Lina

2017-12-01

To evaluate the effect of rehabilitation exercises combined with Direct Vagina Low Voltage Low Frequency Electric Stimulation (DES) on pelvic nerve electrophysiology and tissue function after delivery. Whether and how DES effects pelvic floor dysfunction (PFD) are not known clearly. This was a randomised, controlled clinical trial. The 189 primiparous women 20-35 years old and with an episiotomy or second degree episiotomy tear were divided into three groups: the control group (n = 60) received routine postpartum guidance 2 hr postpartum, the training group (n = 63) performed rehabilitation exercises (Kegel exercises and pelvic movements) from 2 days postpartum until 3 months postpartum, and the combination group (n = 66) received DES 15 times (3 times a week for 30 min at a time) beginning at the sixth week postpartum in addition to performing rehabilitation exercises. Adopt international standard scale and score method to inspect maternal life treatment, such as pelvic organ prolapse situation (POP-Q division), the degree of incontinence score and pelvic floor muscle intensity of muscular contraction. Data were collected during the third month after delivery. Three months postpartum, there were differences among the three groups in the POP-Q grade, the degree of incontinence score, the Oxford grade for pelvic floor muscle strength and the pelvic floor muscle electrophysiology condition. Additionally, there were significant differences regarding the pubic symphysis clearance. Rehabilitation exercises can promote healing of the maternal pubic symphysis and recovery of the pelvis. The total electrical value, type I muscle fibre strength and type II muscle fibre strength were significantly increased in the combination group after treatment than before treatment. Rehabilitation exercises combined with DES were beneficial to the recovery of postpartum pelvic nerve tissue function, and a synergistic effect was observed when the two methods were combined. These conclusions justify that rehabilitation exercise combined with DES can better relieve uncomfortable symptoms postpartum and improve the women's quality of life. © 2017 John Wiley & Sons Ltd.

Adaptive optics optical coherence tomography at 120,000 depth scans/s for non-invasive cellular phenotyping of the living human retina

PubMed Central

Torti, Cristiano; Považay, Boris; Hofer, Bernd; Unterhuber, Angelika; Carroll, Joseph; Ahnelt, Peter Kurt; Drexler, Wolfgang

2012-01-01

This paper presents a successful combination of ultra-high speed (120,000 depth scans/s), ultra-high resolution optical coherence tomography with adaptive optics and an achromatizing lens for compensation of monochromatic and longitudinal chromatic ocular aberrations, respectively, allowing for non-invasive volumetric imaging in normal and pathologic human retinas at cellular resolution. The capability of this imaging system is demonstrated here through preliminary studies by probing cellular intraretinal structures that have not been accessible so far with in vivo, non-invasive, label-free imaging techniques, including pigment epithelial cells, micro-vasculature of the choriocapillaris, single nerve fibre bundles and collagenous plates of the lamina cribrosa in the optic nerve head. In addition, the volumetric extent of cone loss in two colour-blinds could be quantified for the first time. This novel technique provides opportunities to enhance the understanding of retinal pathogenesis and early diagnosis of retinal diseases. PMID:19997159

Neurotoxins from venoms of the Hymenoptera--twenty-five years of research in Amsterdam.

PubMed

Piek, T

1990-01-01

1. In co-operation with colleagues in Europe, Japan and the U.S.A., 25 years of research in Amsterdam have provided new views on the way some hymenopteran insects incapacitate their prey by a diversity of neurotoxins, resulting in block of synaptic transmission in CNS or neuromuscular junctions, or affecting voltage dependent phenomena in nerve and muscle fibers. 2. Nicotinic synaptic transmission in the insect CNS is irreversibly blocked at the presynaptic side by kinins, or reversibly and postsynaptically blocked by philanthotoxins. 3. Glutamatergic neuromuscular transmission is reversibly blocked by philanthotoxins at the pre- and/or postsynaptic side. 4. A presynaptic block of neuromuscular transmission was found with the Microbracon toxins. 5. An irreversible deactivation, without paralysis, of cockroaches is caused by a sting of Ampulex compressa into the suboesophageal ganglion. 6. Poneratoxin, a 25 amino acid residue polypeptide, isolated from an ant venom, is the first described hymenopteran neurotoxin affecting excitability of nerve and muscle fibres by changing the kinetics of the voltage-dependent sodium channel.

Histomorphometric analysis of knee synovial membrane in dogs undergoing leg lengthening by classic Ilizarov method and rapid automatic distraction.

PubMed

Stupina, Tatyana A; Shchudlo, Mikhail M; Shchudlo, Natalia A; Stepanov, Mikhail A

2013-10-01

This pilot study aimed to test the theory that different lengthening methods affect the microscopic structure of knee joint synovium in diverse ways. This was a descriptive and analytical cross-sectional study of synovium carried out in two experimental models of canine leg lengthening using the Ilizarov fixator. Group 1 (n = 6) used manual gradual distraction most commonly used in clinical practice at one millimetre/day divided into four equal increments, 0.25 mm at each increment. Group 2 (n = 7) used an increased rate of automatic distraction at three millimetres/day divided in 120 increments, 0.025 mm at each increment. At the end of distraction and after fixator removal, the animals were euthanised. Control was via intact dogs. The thickness of the synovial lining layer, number of synovial cell rows, and numerical density of subsynovial microvessels were assessed in digital images for semiautomated computerised analysis of semi-thin sections stained with toluidine blue and methylene blue-basic fuchsin. Comparison of synovitis manifestation was made with grading scale. The vascular and nerve changes in the subsynovial layer were also compared. Group 1 developed marked synovitis, synovium hypervascularisation, degeneration of the nerve fibres in subsynovial nerves with the tendency to regeneration. Group 2 had moderate to mild degree of synovitis with progressive degenerative changes in subsynovial vessels and nerves. Both methods used are unfavourable for the state of the joint synovium, but modify it in different ways.

Decreased Axon Flare Reaction to Electrical Stimulation in Patients With Chronic Demyelinating Inflammatory Polyneuropathy.

PubMed

Kokotis, Panagiotis; Schmelz, Martin; Papagianni, Aikaterini E; Zambelis, Thomas; Karandreas, Nikos

2017-03-01

In chronic inflammatory demyelinating polyradiculopathy (CIDP), the impairment of unmyelinated nerve fibers appears unexpected. The measurement of the electrically induced axon flare reflex is a clinical test to assess the peripheral C-nociceptor function. In this study, we compared the flare area in patients suffering from CIDP with healthy subjects. We examined 18 patients fulfilling the criteria for CIDP (11 men, mean age 51.8 years, SD 15.1) and 18 age-matched adult healthy volunteers (control group) (11 men, mean age 51.9 years, SD 15.8). The flare responses were elicited by transcutaneous electrical stimulation and recorded by laser Doppler imaging. There was a significant reduction of electrically induced maximum flare area in the foot dorsum of patients with CIDP (t-value 2.08, P = 0.04) which proved to be length-dependent measured by a numerical index comparing the results with the forearm and thigh. The repeatedmeasures ANOVA revealed statistically significant smaller flare areas in all body regions for the CIDP group (P < 0.001). The axon flare reaction to electrical stimulation was decreased in patients with chronic demyelinating inflammatory polyneuropathy. The evaluation of the axon flare response can be proposed as a noninvasive objective functional test to detect an impaired C-fiber function in CIDP patients with the advantages of simplicity of the procedure, time economy, and objectivity.

Intracellular distributions and putative functions of calcium-binding proteins in the bullfrog vestibular otolith organs

NASA Technical Reports Server (NTRS)

Baird, R. A.; Steyger, P. S.; Schuff, N. R.

1997-01-01

Hair cells in the bullfrog vestibular otolith organs were immunolabeled by monoclonal and polyclonal antisera against calbindin (CaB), calmodulin (CaM), calretinin (CaR), and parvalbumin (PA). S-100, previously shown to immunolabel striolar hair cells in fish vestibular organs, only weakly immunolabeled hair cells in the bullfrog vestibular otolith organs. Immunolabeling was not detected in supporting cells. With the exception of CaR, myelinated axons and unmyelinated nerve terminals were immunolabeled by all of the above antisera. Immunolabeling was seen in all saccular hair cells, although hair cells at the macular margins were immunolabeled more intensely for CaB, CaM, and PA than more centrally located hair cells. As the macula margins are known to be a growth zone, this labeling pattern suggests that marginal hair cells up-regulate their calcium-binding proteins during hair cell development. In the utriculus, immunolabeling for CaM and PA was generally restricted to striolar hair cells. CaR immunolabeling was restricted to the stereociliary array. Immunolabeling for other calcium-binding proteins was generally seen in both the cell body and hair bundles of hair cells, although this labeling was often localized to the stereociliary array and the apical portion of the cell body. CaM and PA immunolabeling in the stereociliary array in saccular and utricular striolar cells suggests a functional role for these proteins in mechanoelectric transduction and adaptation.

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

PubMed Central

Du, Junhui; Zhou, Shengtai; Carlton, Susan M.

2008-01-01

Several lines of evidence indicate that Group II metabotropic glutamate receptor (mGluR) activation can depress sensory transmission. We have reported the expression of Group II mGluRs on unmyelinated axons, many of which were presumed to be nociceptors, in the rat digital nerve (Carlton et al., 2001b). The goals of the present study are to further our understanding of Group II modulation of nociceptor processing in the periphery, documenting behavioral changes using inflammatory models and documenting, for the first time, cutaneous single fiber activity following exposure to a Group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and antagonist LY341495 (LY). The data indicate that peripheral Group II mGluR activation does not depress nociceptive behaviors or nociceptor fiber responses in the non-sensitized state (i.e. following brief nociceptive mechanical or thermal stimulation) but can depress these responses when nociceptors are sensitized by exposure to formalin or inflammatory soup. Group II mGluR agonist-induced inhibition can be blocked by a selective Group II antagonist. Peripheral Group II mGluR-induced inhibition evoked in these studies occurs through activation of local receptors and not through spinal or supraspinal mechanisms. The data indicate that administration of selective Group II agonists may be potent therapeutic agents for prevention of peripheral sensitization and for treatment of inflammatory pain. PMID:18487022

An improved method of crafting a multi-electrode spiral cuff for the selective.

PubMed

Rozman, Janez; Pečlin, Polona; Ribarič, Samo; Godec, Matjaž; Burja, Jaka

2018-01-17

This article reviews an improved methodology and technology for crafting a multi-electrode spiral cuff for the selective activation of nerve fibres in particular superficial regions of a peripheral nerve. The analysis, structural and mechanical properties of the spot welds used for the interconnections between the stimulating electrodes and stainless-steel lead wires are presented. The cuff consisted of 33 platinum electrodes embedded within a self-curling 17-mm-long silicone spiral sheet with a nominal internal diameter of 2.5 mm. The weld was analyzed using scanning electron microscopy and nanohardness tests, while the interconnection was investigated using destructive load tests. The functionality of the cuff was tested in an isolated porcine vagus nerve. The results of the scanning electron microscopy show good alloying and none of the typical welding defects that occur between the wire and the platinum foil. The results of the destructive load tests show that the breaking loads were between 3.22 and 5 N. The results of the nanohardness testing show that the hardness of the weld was different for the particular sites on the weld sample. Finally, the results of the functional testing show that for different stimulation intensities both the compound action potential deflection and the shape are modulated.

A regenerative microchannel neural interface for recording from and stimulating peripheral axons in vivo

NASA Astrophysics Data System (ADS)

FitzGerald, James J.; Lago, Natalia; Benmerah, Samia; Serra, Jordi; Watling, Christopher P.; Cameron, Ruth E.; Tarte, Edward; Lacour, Stéphanie P.; McMahon, Stephen B.; Fawcett, James W.

2012-02-01

Neural interfaces are implanted devices that couple the nervous system to electronic circuitry. They are intended for long term use to control assistive technologies such as muscle stimulators or prosthetics that compensate for loss of function due to injury. Here we present a novel design of interface for peripheral nerves. Recording from axons is complicated by the small size of extracellular potentials and the concentration of current flow at nodes of Ranvier. Confining axons to microchannels of ˜100 µm diameter produces amplified potentials that are independent of node position. After implantation of microchannel arrays into rat sciatic nerve, axons regenerated through the channels forming ‘mini-fascicles’, each typically containing ˜100 myelinated fibres and one or more blood vessels. Regenerated motor axons reconnected to distal muscles, as demonstrated by the recovery of an electromyogram and partial prevention of muscle atrophy. Efferent motor potentials and afferent signals evoked by muscle stretch or cutaneous stimulation were easily recorded from the mini-fascicles and were in the range of 35-170 µV. Individual motor units in distal musculature were activated from channels using stimulus currents in the microampere range. Microchannel interfaces are a potential solution for applications such as prosthetic limb control or enhancing recovery after nerve injury.

Atypical birefringence pattern and the diagnostic ability of scanning laser polarimetry with enhanced corneal compensation in glaucoma.

PubMed

Rao, Harsha L; Yadav, Ravi K; Begum, Viquar U; Addepalli, Uday K; Senthil, Sirisha; Choudhari, Nikhil S; Garudadri, Chandra S

2015-03-01

To evaluate the effect of typical scan score (TSS), when within the acceptable limits, on the diagnostic performance of retinal nerve fibre layer (RNFL) parameters with the enhanced corneal compensation (ECC) protocol of scanning laser polarimetry (SLP) in glaucoma. In a cross-sectional study, 203 eyes of 160 glaucoma patients and 140 eyes of 104 control subjects underwent RNFL imaging with the ECC protocol of SLP. TSS was used to quantify atypical birefringence pattern (ABP) images. Influence of TSS on the diagnostic ability of SLP parameters was evaluated by receiver operating characteristic (ROC) regression models after adjusting for the effect of disease severity [based on mean deviation (MD)] on standard automated perimetry). Diagnostic abilities of all RNFL parameters of SLP increased when the TSS values were higher. This effect was statistically significant for TSNIT (coefficient: 0.08, p<0.001) and inferior average parameters (coefficient: 0.06, p=0.002) but not for nerve fibre indicator (NFI, coefficient: 0.03, p=0.21). In early glaucoma (MD of -5 dB), predicted area under ROC curve (AUC) for TSNIT average parameter improved from 0.642 at a TSS of 90 to 0.845 at a TSS of 100. In advanced glaucoma (MD of -15 dB), AUC for TSNIT average improved from 0.832 at a TSS of 90 to 0.947 at 100. Diagnostic performances of TSNIT and inferior average RNFL parameters with ECC protocol of SLP were significantly influenced by TSS even when the TSS values were within the acceptable limits. Diagnostic ability of NFI was unaffected by TSS values. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Functional expression of ionotropic purinergic receptors on mouse taste bud cells.

PubMed

Hayato, Ryotaro; Ohtubo, Yoshitaka; Yoshii, Kiyonori

2007-10-15

Neurotransmitter receptors on taste bud cells (TBCs) and taste nerve fibres are likely to contribute to taste transduction by mediating the interaction among TBCs and that between TBCs and taste nerve fibres. We investigated the functional expression of P2 receptor subtypes on TBCs of mouse fungiform papillae. Electrophysiological studies showed that 100 microm ATP applied to their basolateral membranes either depolarized or hyperpolarized a few cells per taste bud. Ca(2+) imaging showed that similarly applied 1 mum ATP, 30 microm BzATP (a P2X(7) agonist), or 1 microm 2MeSATP (a P2Y(1) and P2Y(11) agonist) increased intracellular Ca(2+) concentration, but 100 microm UTP (a P2Y(2) and P2Y(4) agonist) and alpha,beta-meATP (a P2X agonist except for P2X(2), P2X(4) and P2X(7)) did not. RT-PCR suggested the expression of P2X(2), P2X(4), P2X(7), P2Y(1), P2Y(13) and P2Y(14) among the seven P2X subtypes and seven P2Y subtypes examined. Immunohistostaining confirmed the expression of P2X(2). The exposure of the basolateral membranes to 3 mm ATP for 30 min caused the uptake of Lucifer Yellow CH in a few TBCs per taste bud. This was antagonized by 100 microm PPADS (a non-selective P2 blocker) and 1 microm KN-62 (a P2X(7) blocker). These results showed for the first time the functional expression of P2X(2) and P2X(7) on TBCs. The roles of P2 receptor subtypes in the taste transduction, and the renewal of TBCs, are discussed.

The association between clinical parameters and glaucoma-specific quality of life in Chinese primary open-angle glaucoma patients.

PubMed

Lee, Jacky W Y; Chan, Catherine W S; Chan, Jonathan C H; Li, Q; Lai, Jimmy S M

2014-08-01

OBJECTIVE. To investigate the association between clinical measurements and glaucoma-specific quality of life in Chinese glaucoma patients. DESIGN. Cross-sectional study. SETTING. An academic hospital in Hong Kong. PATIENTS. A Chinese translation of the Glaucoma Quality of Life-15 questionnaire was completed by 51 consecutive patients with bilateral primary open-angle glaucoma. The binocular means of several clinical measurements were correlated with Glaucoma Quality of Life-15 findings using Pearson's correlation coefficient and linear regression. The measurements were the visual field index and pattern standard deviation from the Humphrey Field Analyzer, Snellen best-corrected visual acuity, presenting intra-ocular pressure, current intra-ocular pressure, average retinal nerve fibre layer thickness via optical coherence tomography, and the number of topical anti-glaucoma medications being used. RESULTS. In these patients, there was a significant correlation and linear relationship between a poorer Glaucoma Quality of Life-15 score and a lower visual field index (r=0.3, r(2)=0.1, P=0.01) and visual acuity (r=0.3, r(2)=0.1, P=0.03). A thinner retinal nerve fibre layer also correlated with a poorer Glaucoma Quality of Life-15 score, but did not attain statistical significance (r=0.3, P=0.07). There were no statistically significant correlations for the other clinical parameters with the Glaucoma Quality of Life-15 scores (all P values being >0.7). The three most problematic activities affecting quality of life were "adjusting to bright lights", "going from a light to a dark room or vice versa", and "seeing at night". CONCLUSION. For Chinese primary open-angle glaucoma patients, binocular visual field index and visual acuity correlated linearly with glaucoma-specific quality of life, and activities involving dark adaptation were the most problematic.

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy

PubMed Central

Balestrini, Simona; Clayton, Lisa M S; Bartmann, Ana P; Chinthapalli, Krishna; Novy, Jan; Coppola, Antonietta; Wandschneider, Britta; Stern, William M; Acheson, James; Bell, Gail S; Sander, Josemir W; Sisodiya, Sanjay M

2016-01-01

Objective Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter ‘integrity’. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy. Methods Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study. RNFL imaging was performed using spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of adequate trials of two antiepileptic drugs to achieve sustained seizure freedom. Results The average RNFL thickness and the thickness of each of the 90° quadrants were significantly thinner in people with epilepsy than healthy controls (p<0.001, t test). In a multivariate logistic regression model, drug resistance was the only significant predictor of abnormal RNFL thinning (OR=2.09, 95% CI 1.09 to 4.01, p=0.03). Duration of epilepsy (coefficient −0.16, p=0.004) and presence of intellectual disability (coefficient −4.0, p=0.044) also showed a significant relationship with RNFL thinning in a multivariate linear regression model. Conclusions Our results suggest that people with epilepsy with no previous exposure to vigabatrin have a significantly thinner RNFL than healthy participants. Drug resistance emerged as a significant independent predictor of RNFL borderline attenuation or abnormal thinning in a logistic regression model. As this is easily assessed by OCT, RNFL thickness might be used to better understand the mechanisms underlying drug resistance, and possibly severity. Longitudinal studies are needed to confirm our findings. PMID:25886782

Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

PubMed Central

2010-01-01

Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS), considered a neuropathic orofacial pain disorder. Methods Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5) and controls (n = 12), and the other patients with BMS (n = 7) and controls (n = 10). BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS). Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Nav1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results There was a significantly increased visual intensity score for Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS. PMID:20529324

Percutaneous renal sympathetic nerve ablation for loin pain haematuria syndrome.

PubMed

Gambaro, Giovanni; Fulignati, Pierluigi; Spinelli, Alessio; Rovella, Valentina; Di Daniele, Nicola

2013-09-01

Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular.

Prevalent involvement of thenar motor fibres in vineyard workers with carpal tunnel syndrome.

PubMed

Mondelli, M; Baldasseroni, A; Aretini, A; Ginanneschi, F; Padua, L

2010-08-01

Carpal tunnel syndrome (CTS) has a high prevalence in agricultural workers, especially those engaged in vineyards. We postulated that vineyard CTS was electrophysiologically different from CTS of other subjects. We performed a retrospective cross-sectional electrophysiological study of two cohorts of consecutive patients with CTS, the first consisting of vineyard workers and the second, of other unselected types of workers, housewives and pensioners. Thirty-three vineyard workers (mean age 46.8years, 42% women) and 205 patients with other occupations (mean age 53.7years; 66% women) were enrolled. All patients underwent sensory and motor neurography of the median and ulnar nerves. Differences in demographic and electrophysiological findings between groups were calculated and multiple linear regression analysis was performed to eliminate the influence of potential confounding factors (age, sex, BMI, clinical severity of CTS) on the results of univariate difference analysis. Univariate analysis showed that DML was longer and compound muscle action potential amplitude of the median nerve, recorded from the abductor pollicis brevis muscle, was smaller in vineyard workers than in the other CTS patients. These differences remained significant after adjusting the results for confounding factors. The vineyard workers showed a different pattern of CTS than the other patients: thenar motor fibres were more affected, presumably due to chronic compression on the thenar branch. This suggests an association between "common" CTS and thenar mononeuropathy. Occupational physiologists should clarify the mechanisms of neuromuscular engagement in particular jobs and ergonomists design suitable working tools, because many "individual" risk factors are difficult to change, but workplace-related risk factors can be modified. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Machine learning classifiers for glaucoma diagnosis based on classification of retinal nerve fibre layer thickness parameters measured by Stratus OCT.

PubMed

Bizios, Dimitrios; Heijl, Anders; Hougaard, Jesper Leth; Bengtsson, Boel

2010-02-01

To compare the performance of two machine learning classifiers (MLCs), artificial neural networks (ANNs) and support vector machines (SVMs), with input based on retinal nerve fibre layer thickness (RNFLT) measurements by optical coherence tomography (OCT), on the diagnosis of glaucoma, and to assess the effects of different input parameters. We analysed Stratus OCT data from 90 healthy persons and 62 glaucoma patients. Performance of MLCs was compared using conventional OCT RNFLT parameters plus novel parameters such as minimum RNFLT values, 10th and 90th percentiles of measured RNFLT, and transformations of A-scan measurements. For each input parameter and MLC, the area under the receiver operating characteristic curve (AROC) was calculated. There were no statistically significant differences between ANNs and SVMs. The best AROCs for both ANN (0.982, 95%CI: 0.966-0.999) and SVM (0.989, 95% CI: 0.979-1.0) were based on input of transformed A-scan measurements. Our SVM trained on this input performed better than ANNs or SVMs trained on any of the single RNFLT parameters (p < or = 0.038). The performance of ANNs and SVMs trained on minimum thickness values and the 10th and 90th percentiles were at least as good as ANNs and SVMs with input based on the conventional RNFLT parameters. No differences between ANN and SVM were observed in this study. Both MLCs performed very well, with similar diagnostic performance. Input parameters have a larger impact on diagnostic performance than the type of machine classifier. Our results suggest that parameters based on transformed A-scan thickness measurements of the RNFL processed by machine classifiers can improve OCT-based glaucoma diagnosis.

Rates of retinal nerve fibre layer thickness change in glaucoma patients and control subjects

PubMed Central

O'Leary, N; Artes, P H; Hutchison, D M; Nicolela, M T; Chauhan, B C

2012-01-01

Purpose To examine the rates of retinal nerve fibre layer thickness (RNFLT) change in glaucoma patients and healthy, age-similar control subjects with three techniques: scanning laser polarimetry with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and time-domain optical coherence tomography (OCT). Methods Sixty-one patients and thirty-three controls were examined with each technique and with standard automated perimetry (SAP) every 6 months. Rates of global RNFLT change and SAP mean deviation (MD) change were estimated with linear mixed-effects models. Results The median (interquartile range) baseline age was 64.4 (58.2, 71.0) years for patients and 62.4 (56.3, 70.1) years for controls (P=0.56). There was a median of seven examinations over 3.1 years for patients and six examinations in 3.0 years for controls. Baseline visual field MD and RNFLT for all imaging modalities were significantly lower (P<0.01) in patients compared with controls. Rates of RNFLT change were not significantly different between patients and controls (P≥0.19). Mean rates of VCC-measured RNFLT change were −0.18 and −0.37 μm per year in patients and controls, whereas the respective figures for ECC and OCT were −0.13 and −0.31 μm per year, and 0.04 and 0.61 μm per year. Mean rates of MD change were −0.20 and 0.03 dB per year in patients and controls, respectively (P=0.01). Conclusion Rates of RNFLT change in glaucoma patients were not statistically different from control subjects for any modality. A significantly negative rate of MD change in patients suggests a genuine, continued deterioration in these patients not reflected by RNFLT changes. PMID:23079756

Membrane potential oscillations are not essential for spontaneous firing generation in L4 Aβ-afferent neurons after L5-spinal nerve axotomy and are not mediated by HCN channels.

PubMed

Djouhri, L; Smith, T; Alotaibi, M; Weng, X

2018-06-03

What is the central question of this study? Is spontaneous activity (SA) in L4-DRG neurons induced by L5 spinal nerve axotomy is associated with membrane potentials oscillations in theses neurons, and are these membrane oscillations mediated by HCN channels? What is the main finding and its importance? Unlike injured L5 DRG neurons which have been shown to be incapable of firing spontaneously without membrane potentials oscillations, such membrane oscillations are not essential for SA generation in conducting "uninjured'' L4 neurons, and they are not mediated by HCN channels. These findings suggest that the underlying cellular mechanisms of SA in injured and "uninjured'' DRG neurons induced by spinal nerve injury are distinct. The underlying cellular and molecular mechanisms of peripheral neuropathic pain are not fully understood. However, preclinical studies using animal models of this debilitating condition suggest that it is driven partly by aberrant spontaneous activity (SA) in injured and uninjured dorsal root ganglion (DRG) neurons, and that SA in injured DRG neurons is triggered by subthreshold membrane potential oscillations (SMPOs). Here, using in vivo intracellular recording from control L4-DRG neurons, and ipsilateral L4-DRG neurons in female Wistar rats that had previously undergone L5-spinal nerve axotomy (SNA), we examined whether conducting 'uninjured' L4-DRG neurons in SNA rats exhibit SMPOs, and if so, whether such SMPOs are associated with SA in those L4-neurons, and whether they are mediated by hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We found that 7-days after SNA: (a) none of control A- or C-fibre DRG neurons showed SMPOs or SA, but 50%, 43% and 0% of spontaneously active cutaneous L4 Aβ-low threshold mechanoreceptors, Aβ-nociceptors and C-nociceptors exhibited SMPOs respectively in SNA rats with established neuropathic pain behaviors, (b) neither SMPOs nor SA in L4 Aβ-neurons were suppressed by blocking HCN channels with ZD7288 (10 mg/kg, i.v.) and (c) there is a tendency for female rats to show greater pain hypersensitivity than male rats. These results suggest that SMPOs are linked to SA only in some of the conducting L4 Aβ-neurons, that such oscillations are not a prerequisite for SA generation in those L4 A- or C-fibre neurons, and that HCN channels are not involved in their electrogenesis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tactile Perception in Adults with Autism: A Multidimensional Psychophysical Study

ERIC Educational Resources Information Center

Cascio, Carissa; McGlone, Francis; Folger, Stephen; Tannan, Vinay; Baranek, Grace; Pelphrey, Kevin A.; Essick, Gregory

2008-01-01

Although sensory problems, including unusual tactile sensitivity, are heavily associated with autism, there is a dearth of rigorous psychophysical research. We compared tactile sensation in adults with autism to controls on the palm and forearm, the latter innervated by low-threshold unmyelinated afferents subserving a social/affiliative…

Expression and localization in the developing cerebellum of the carbohydrate epitopes revealed by Elec-39, an IgM monoclonal antibody related to HNK-1.

PubMed

Kuchler, S; Zanetta, J P; Bon, S; Zaepfel, M; Massoulie, J; Vincendon, G

1991-01-01

The immunochemical and immunocytochemical reactivity of an anti-carbohydrate monoclonal antibody (Elec-39), obtained against acetylcholinesterase from Electrophorus electricus electric organ, was followed during the postnatal development of the rat cerebellum. The specificity of this antibody resembles that of a family of anti-carbohydrate antibodies that includes HNK-1, L2, NC-1 and NSP-4, as well as IgMs that occur in some human neuropathies. As revealed by immunoblotting techniques, the reactivity of Elec-39 is maximum around postnatal days 10-12. At this age, the antibody reveals eight major proteins of mol. wt ranging between 14 and 150 kDa. Some of them (with mol. wts of 14, 18, 28 and 31 kDa) are transiently expressed. They correspond to previously identified glycoproteins binding to the plant lectin concanavalin A and binding also to the endogenous mannose-binding lectin CSL and endogenous membrane-bound mannose-binding lectin. In young animals, an important staining with the Elec-39 antibody can be observed on postmitotic precursors of granule cells, on astrocyte processes in the external granular layer, on newly formed parallel fibres and on unmyelinated axons of the white matter. In adult animals, the labelling is localized essentially in myelin and also in the cytoplasm of astrocytes. These results are discussed in relation to ontogenetic phenomena occurring during cerebellar development and the potential role of the carbohydrate epitope revealed with Elec-39 as a determinant in cell adhesion processes.

Innervation of the rabbit cardiac ventricles.

PubMed

Pauziene, Neringa; Alaburda, Paulius; Rysevaite-Kyguoliene, Kristina; Pauza, Audrys G; Inokaitis, Hermanas; Masaityte, Aiste; Rudokaite, Gabriele; Saburkina, Inga; Plisiene, Jurgita; Pauza, Dainius H

2016-01-01

The rabbit is widely used in experimental cardiac physiology, but the neuroanatomy of the rabbit heart remains insufficiently examined. This study aimed to ascertain the architecture of the intrinsic nerve plexus in the walls and septum of rabbit cardiac ventricles. In 51 rabbit hearts, a combined approach involving: (i) histochemical acetylcholinesterase staining of intrinsic neural structures in total cardiac ventricles; (ii) immunofluorescent labelling of intrinsic nerves, nerve fibres (NFs) and neuronal somata (NS); and (iii) transmission electron microscopy of intrinsic ventricular nerves and NFs was used. Mediastinal nerves access the ventral and lateral surfaces of both ventricles at a restricted site between the root of the ascending aorta and the pulmonary trunk. The dorsal surface of both ventricles is supplied by several epicardial nerves extending from the left dorsal ganglionated nerve subplexus on the dorsal left atrium. Ventral accessing nerves are thicker and more numerous than dorsal nerves. Intrinsic ventricular NS are rare on the conus arteriosus and the root of the pulmonary trunk. The number of ventricular NS ranged from 11 to 220 per heart. Four chemical phenotypes of NS within ventricular ganglia were identified, i.e. ganglionic cells positive for choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and biphenotypic, i.e. positive for both ChAT/nNOS and for ChAT/tyrosine hydroxylase. Clusters of small intensely fluorescent cells are distributed within or close to ganglia on the root of the pulmonary trunk, but not on the conus arteriosus. The largest and most numerous intrinsic nerves proceed within the epicardium. Scarce nerves were found near myocardial blood vessels, but the myocardium contained only a scarce meshwork of NFs. In the endocardium, large numbers of thin nerves and NFs proceed along the bundle of His and both its branches up to the apex of the ventricles. The endocardial meshwork of fine NFs was approximately eight times denser than the myocardial meshwork. Adrenergic NFs predominate considerably in all layers of the ventricular walls and septum, whereas NFs of other neurochemical phenotypes were in the minority and their amount differed between the epicardium, myocardium and endocardium. The densities of NFs positive for nNOS and ChAT were similar in the epicardium and endocardium, but NFs positive for nNOS in the myocardium were eight times more abundant than NFs positive for ChAT. Potentially sensory NFs positive for both calcitonin gene-related peptide and substance P were sparse in the myocardial layer, but numerous in epicardial nerves and particularly abundant within the endocardium. Electron microscopic observations demonstrate that intrinsic ventricular nerves have a distinctive morphology, which may be attributed to remodelling of the peripheral nerves after their access into the ventricular wall. In conclusion, the rabbit ventricles display complex structural organization of intrinsic ventricular nerves, NFs and ganglionic cells. The results provide a basic anatomical background for further functional analysis of the intrinsic nervous system in the cardiac ventricles. © 2015 Anatomical Society.

Pharmacology of pH effects on carotid body chemoreceptors in vitro.

PubMed

Eyzaguirre, C; Zapata, P

1968-04-01

1. The carotid body and the carotid nerve were removed from anaesthetized cats and placed in a small Perspex channel through which Locke solution (at various pH values and usually equilibrated with 50% O(2) in N(2)) was allowed to flow. The glomus was immersed in the flowing solution while the nerve was lifted into oil covering the saline. Sensory discharges were recorded from the nerve and their frequency was used as an index of receptor activity. At times, a small segment of carotid artery, containing pressoreceptor endings, was removed together with the glomus. In this case, pressoreceptor discharges were recorded from the nerve.2. The amplitude of either chemo- or pressoreceptor discharges was not changed by strong acid solutions. Acid decreased the frequency of the baroreceptor discharges only when pH fell to less than 4.0. Solutions at low pH increased the chemosensory discharge, but acid depressed the increased chemoreceptor discharge elicited by KCl. These experiments indicated that H(+) ions probably acted as membrane ;stabilizers' without depolarizing either the nerve fibres or endings.3. Acid solutions increased the action of acetylcholine chloride (AChCl) (100-200 mug) on chemoreceptors. This effect probably was due either to inactivation of tissue cholinesterase or to enhanced sensitivity of the sensory endings to ACh.4. Choline chloride (10(-3)M), which favours ACh synthesis, protected the preparation against decay during prolonged experimentation. Hemicholinium-3 (HC-3), which blocks ACh synthesis in low concentrations (10(-5)M), depressed the chemosensory response to acid and to hypoxia when such stimuli were applied repeatedly. This concentration of HC-3 did not change effects of applied ACh.5. Substances which affect ACh release markedly changed the chemoreceptor discharge increase induced by acidity and other forms of stimulation. In the absence of Ca(2+), acid, anoxia, and interruption of flow provoked receptor depression while receptor excitation induced by ACh and KCl persisted. All stimuli excited and showed increased effectiveness as the Ca(2+) concentration was raised, but their effects declined as Ca(2+) was increased above normal values. Mg(2+) ions depressed the chemoreceptor effects induced by all these stimuli. The action of Mg(2+) was not due entirely to nerve ending block. Morphine sulphate (which decreases ACh release in other structures) also depressed the receptor response to acid and flow interruption.6. Cholinergic blocking agents such as mecamylamine, hexamethonium, atropine, dihydro-beta-erithroidine (DHE), HC-3 (10(-4)M), choline and acetylcholine (in combination with choline) depressed the effects of acid and ACh on the chemoreceptors. The effect induced by interruption of flow was depressed only by mecamylamine and DHE.7. Agents which affect the fate of released ACh, such as acetylcholinesterase and eserine salicylate, did not affect clearly the response of chemoreceptors to acid.8. The results suggest that acid stimulates chemoreceptor fibres through an indirect mechanism, viz. through increased release and/or decreased destruction of a presynaptic transmitter from the glomus cell. This transmitter is probably ACh (see following paper, Eyzaguirre & Zapata, 1968).

Pharmacology of pH effects on carotid body chemoreceptors in vitro

PubMed Central

Eyzaguirre, C.; Zapata, P.

1968-01-01

1. The carotid body and the carotid nerve were removed from anaesthetized cats and placed in a small Perspex channel through which Locke solution (at various pH values and usually equilibrated with 50% O2 in N2) was allowed to flow. The glomus was immersed in the flowing solution while the nerve was lifted into oil covering the saline. Sensory discharges were recorded from the nerve and their frequency was used as an index of receptor activity. At times, a small segment of carotid artery, containing pressoreceptor endings, was removed together with the glomus. In this case, pressoreceptor discharges were recorded from the nerve. 2. The amplitude of either chemo- or pressoreceptor discharges was not changed by strong acid solutions. Acid decreased the frequency of the baroreceptor discharges only when pH fell to less than 4·0. Solutions at low pH increased the chemosensory discharge, but acid depressed the increased chemoreceptor discharge elicited by KCl. These experiments indicated that H+ ions probably acted as membrane `stabilizers' without depolarizing either the nerve fibres or endings. 3. Acid solutions increased the action of acetylcholine chloride (AChCl) (100-200 μg) on chemoreceptors. This effect probably was due either to inactivation of tissue cholinesterase or to enhanced sensitivity of the sensory endings to ACh. 4. Choline chloride (10-3 M), which favours ACh synthesis, protected the preparation against decay during prolonged experimentation. Hemicholinium-3 (HC-3), which blocks ACh synthesis in low concentrations (10-5 M), depressed the chemosensory response to acid and to hypoxia when such stimuli were applied repeatedly. This concentration of HC-3 did not change effects of applied ACh. 5. Substances which affect ACh release markedly changed the chemoreceptor discharge increase induced by acidity and other forms of stimulation. In the absence of Ca2+, acid, anoxia, and interruption of flow provoked receptor depression while receptor excitation induced by ACh and KCl persisted. All stimuli excited and showed increased effectiveness as the Ca2+ concentration was raised, but their effects declined as Ca2+ was increased above normal values. Mg2+ ions depressed the chemoreceptor effects induced by all these stimuli. The action of Mg2+ was not due entirely to nerve ending block. Morphine sulphate (which decreases ACh release in other structures) also depressed the receptor response to acid and flow interruption. 6. Cholinergic blocking agents such as mecamylamine, hexamethonium, atropine, dihydro-β-erithroidine (DHE), HC-3 (10-4 M), choline and acetylcholine (in combination with choline) depressed the effects of acid and ACh on the chemoreceptors. The effect induced by interruption of flow was depressed only by mecamylamine and DHE. 7. Agents which affect the fate of released ACh, such as acetylcholinesterase and eserine salicylate, did not affect clearly the response of chemoreceptors to acid. 8. The results suggest that acid stimulates chemoreceptor fibres through an indirect mechanism, viz. through increased release and/or decreased destruction of a presynaptic transmitter from the glomus cell. This transmitter is probably ACh (see following paper, Eyzaguirre & Zapata, 1968). PMID:4296975

Neuropathic pain: is quantitative sensory testing helpful?

PubMed

Krumova, Elena K; Geber, Christian; Westermann, Andrea; Maier, Christoph

2012-08-01

Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory system and is characterised by a combination of positive and negative sensory symptoms. Quantitative sensory testing (QST) examines the sensory perception after application of different mechanical and thermal stimuli of controlled intensity and the function of both large (A-beta) and small (A-delta and C) nerve fibres, including the corresponding central pathways. QST can be used to determine detection, pain thresholds and stimulus-response curves and can thus detect both negative and positive sensory signs, the second ones not being assessed by other methods. Similarly to all other psychophysical tests QST requires standardised examination, instructions and data evaluation to receive valid and reliable results. Since normative data are available, QST can contribute also to the individual diagnosis of neuropathy, especially in the case of isolated small-fibre neuropathy, in contrast to the conventional electrophysiology which assesses only large myelinated fibres. For example, detection of early stages of subclinical neuropathy in symptomatic or asymptomatic patients with diabetes mellitus can be helpful to optimise treatment and identify diabetic foot at risk of ulceration. QST assessed the individual's sensory profile and thus can be valuable to evaluate the underlying pain mechanisms which occur in different frequencies even in the same neuropathic pain syndromes. Furthermore, assessing the exact sensory phenotype by QST might be useful in the future to identify responders to certain treatments in accordance to the underlying pain mechanisms.

Novel, posterior sensory organ in the trochophore larva of Phyllodoce maculata (Polychaeta).

PubMed Central

Nezlin, L P; Voronezhskaya, E E

2003-01-01

A new posterior sensory organ (PSO), located at the dorsal midline of the hyposphere, is described by immunocytochemical detection of acetylated alpha tubulin and serotonin (5-HT) in a laser-scanning microscope, as well as three-dimensional reconstructions after optical serial sectioning in the trochophore larva of the polychaete Phyllodoce maculata (Phyllodocidae). The unpaired PSO consists of five bipolar sensory cells, two of them being 5-HT immunopositive, which send axons to the cerebral ganglion and prototroch nerve. The dendrites of these cells project to the surface and bear one cilium each. A single neuronal fibre from the apical sensory organ innervates the PSO. PMID:14667369

OFO experimental techniques and preliminary conclusions - Is artificial gravity needed during prolonged weightlessness.

NASA Technical Reports Server (NTRS)

Gualtierotti, T.; Bracchi, F.

1972-01-01

The technique of single unit recording from body systems generating electrical pulses coherent with their basic function (CNS, muscles, sense organs) has been proved feasible during the OFO A orbital flight, an automatic physiological experiment. The results of recording 155 hours of orbital flight of pulses from the nerve fibres of four vestibular gravity sensors in two bull frogs indicate that the vestibular organ adjusts to zero g. As all the other biological changes observed during orbit are due to lack of exercise, it is concluded that artificial gravity might not be necessary during prolonged space missions or on low gravity celestial bodies.

On the distributive patterns of ATPase activity and its functional significance in retinae of certain birds.

PubMed

Tewari, H B; Tyagi, H R

1977-01-01

The present study incorporates the details of distribution of adenosine triphosphatase amongst the various constituents of retinae of Passer, Psittacula, Streptopelia and Athene. The outer segments in all the cases are intensely positive for the enzyme. This is the part where the light strikes first and initiates the visual processes. The nuclear layers are also positive for the enzyme activity. It is interesting to note that inner plexiform layers show clear-out demarcations of various sub-synaptic layers in all the birds except Psittacula. The ganglion cells and optic nerve fibres are also positive for the enzyme.

Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice.

PubMed

Mabe, Abigail M; Hoover, Donald B

2009-04-01

Previous work provided indirect evidence that the neurotrophic factor neurturin (NRTN) is required for normal cholinergic innervation of the heart. This study used nrtn knockout (KO) and wild-type (WT) mice to determine the effect of nrtn deletion on cardiac cholinergic innervation and function in the adult heart. Immunohistochemistry, confocal microscopy, and quantitative image analysis were used to directly evaluate intrinsic cardiac neuronal development. Atrial acetylcholine (ACh) levels were determined as an indirect index of cholinergic innervation. Cholinergic function was evaluated by measuring negative chronotropic responses to right vagal nerve stimulation in anaesthetized mice and responses of isolated atria to muscarinic agonists. KO hearts contained only 35% the normal number of cholinergic neurons, and the residual cholinergic neurons were 15% smaller than in WT. Cholinergic nerve density at the sinoatrial node was reduced by 87% in KOs, but noradrenergic nerve density was unaffected. Atrial ACh levels were substantially lower in KO mice (0.013 +/- 0.004 vs. 0.050 +/- 0.011 pmol/microg protein; P < 0.02) as expected from cholinergic neuron and nerve fibre deficits. Maximum bradycardia evoked by vagal stimulation was reduced in KO mice (38 +/- 6% vs. 69 +/- 3% decrease at 20 Hz; P < 0.001), and chronotropic responses took longer to develop and fade. In contrast to these deficits, isolated atria from KO mice had normal post-junctional sensitivity to carbachol and bethanechol. These findings demonstrate that NRTN is essential for normal cardiac cholinergic innervation and cholinergic control of heart rate. The presence of residual cardiac cholinergic neurons and vagal bradycardia in KO mice suggests that additional neurotrophic factors may influence this system.

Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

PubMed

Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

2017-09-27

Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the brain. Copyright © 2017 the authors 0270-6474/17/379519-15$15.00/0.

Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms.

PubMed

Egerod, Kristoffer L; Petersen, Natalia; Timshel, Pascal N; Rekling, Jens C; Wang, Yibing; Liu, Qinghua; Schwartz, Thue W; Gautron, Laurent

2018-06-01

G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract. Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Na v 1.8-expressing afferents. GPCRs for gut hormones that were the most enriched in Na v 1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Na v 1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Na v 1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Ramus marginalis mandibulae nervus facialis palsy in hemifacial microsomia.

PubMed

Silvestri, A; Mariani, G; Vernucci, R A

2008-12-01

The paralysis of the ramus marginalis mandibulae nervus facialis may occur in Hemifacial Microsomia (HM); the combination of both HM and palsy contributes to an elongation of the mandibular body. This study explores a possible correlation between neurological deficit, muscular atony, and structural deficiency. Of 58 patients with HM who had come to the University of Rome (Sapienza) Pre-surgical Orthodontics Unit, 4 patients were afflicted with Hemifacial Microsomia and ramus marginalis mandibulae nervus palsy; these patients underwent physical, neurological, opthamologic and systemic examinations. The results were then analysed in order to determine a possible correlation between neuro-muscular and structural deficit. Electroneurographic and electromyographic examinations were performed to estimate facial nerve and muscles involvement. Neuroelectrographic exam showed a damage of the nervous motor fibres of the facial nerve ipsilateral to HM, with an associated damage of the muscular function, while neuro-muscular functions on the healthy side were normal. The peripheral nervous and muscular deficits affect the function of facial soft tissues and the growth of mandibular body with an asymmetry characterised by a hypodevelopment of the ramus (due to the HM) and by an elongation of the mandibular body (due to ramus marginalis mandibulae nerve palsy), so that the chin deviation is contralateral to HM. In these forms, a neurological examination is necessary to assess the neurological damage on the HM side. Neuromuscular deficiency can also contribute to a relapse tendency after a surgical-orthodontic treatment.

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis.

PubMed

Kolbe, Scott C; van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F; Kilpatrick, Trevor J

2016-01-01

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis

PubMed Central

van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F.; Kilpatrick, Trevor J.

2016-01-01

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of −2.6% per annum (control = −0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = −0.428, p = 0.009; MD: R = −0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage. PMID:27555964

Kinetics of activation of a Ca2+-dependent K+ current induced by flash photolysis of caged carbachol in isolated guinea-pig outer hair cells.

PubMed

Chan, E; Evans, M G

1998-09-18

It has been shown that the application of acetylcholine activates a Ca2+-dependent K+ current in outer hair cells, and the resulting hyperpolarization is thought to be an important part of the inhibition mediated by cholinergic efferent nerve fibres to the cochlea. In order to study the kinetics of the current, flash photolysis has been used to apply a cholinergic agonist, carbachol, rapidly to isolated outer hair cells. A delay in the onset of the outward potassium current following photorelease of carbachol was consistently observed, and the activation phase of the response could be described by a sigmoidal-like function with a mean delay of 59 ms and time constant of 71 ms. The sum of these values lies within the time scale reported for the onset of the inhibition following electrical stimulation of the efferent nerves. Although a distinct current attributable to an acetylcholine receptor was not visible in these experiments, indirect evidence for a carbachol-induced influx of Ca2+ was obtained.

The actions of volatile anaesthetics on synaptic transmission in the dentate gyrus.

PubMed Central

Richards, C D; White, A E

1975-01-01

1. The action of four volatile anaesthetics on the evoked synaptic potentials of in vitro preparations of the hippocampus were examined. 2. All four anaesthetics (ether, halothane, methoxyflurane and trichloroethylene) depressed the synaptic transmission between the perforant path and the granule cells at concentrations lower than those required to maintain anaesthesia in intact animals. 3. The population excitatory post-synaptic potential (e.p.s.p.) and massed discharge of the cortical cells (population spike) were depressed at concentrations of the anaesthetics lower than those required to depress the compound action potential of the perforant path nerve fibres. None of the anaesthetics studied increased the threshold depolarization required for granule cell discharge. Furthermore, frequency potentiation of the evoked cortical e.p.s.p.s was not impaired by any of the anaesthetics studied. 4. It is concluded that all four anaesthetics depress synaptic transmission in the dentate gyrus either by reducing the amount of transmitter released from each nerve terminal in response to an afferent volley, or by decreasing the sensitivity of the post-synaptic membrane to released transmitted or by both effects together. PMID:1202196

Circumvallate papilla of dog following suture of the hypoglossal and glossopharyngeal nerves.

PubMed

State, F A

1977-01-01

20 adult dogs were classified into five groups; in two animals of each group hypoglossa-glossopharyngeal suturing was done. In the other two animals glossopharyngeal nerve transection with concomitant central segment avulsion was done and these two animals were used as controls. The animals of the five groups were sacrified at 4-week intervals starting by the first group on the 4th post-operative week and ending by the fifth group on the 20th week; the circumvallate papillae were studied. On the 4th week following either operative procedure, few taste buds persisted on the circumvallate papillae. Invasion of the papillae by regenerating hypoglossal fibres from the 8th week onwards was not followed by any appreciable increase in the number of taste buds. The difference in number of taste buds between hypoglossal-glossopharyngeal suture and glossopharyngeal avulsion procedures was not statistically significant. from the 8th weeks following cross-innervation the reaction for acetylcholinesterase was more intense than in denervated papillae which showed a persistent weakly positive reaction up to the 20th post-operative week.

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

PubMed Central

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

2011-01-01

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

Autonomic innervation of the muscles in the wall of the bladder and proximal urethra of male rats.

PubMed Central

Watanabe, H; Yamamoto, T Y

1979-01-01

The muscular coat of the body of the rat bladder is innervated almost exclusively by cholinergic endings:adrenergic endings are rare. In the inner longitudinal muscle layer of the proximal urethra, 53% of 310 autonomic nerve endings observed in close relation to the smooth muscle cells were adrenergic and the remaining 47% cholinergic. The middle circular muscle layer of the proximal urethra was innervated predominantly by adrenergic endings: in this layer 86% of the total of 335 endings examined wre regarded as adrenergic. A similar predominantly adrenergic innervation was noted in the outer longitudinal layer of the proximal urethra. A number of striated muscle fibres arose from the outermost striated muscle layer of the proximal urethra and intruded deeply into the outer and middle smooth muscle layers. These intruding striated muscle fibres also received direct autonomic (mostly adrenergic) innervation. The significance of these findings in relation to the physiology of the lower urinary tracts is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 PMID:489473

Modulation of the masseteric reflex by gastric vagal afferents.

PubMed

Pettorossi, V E

1983-04-01

Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.

Effectiveness of averaging strategies to reduce variance in retinal nerve fibre layer thickness measurements using spectral-domain optical coherence tomography.

PubMed

Pemp, Berthold; Kardon, Randy H; Kircher, Karl; Pernicka, Elisabeth; Schmidt-Erfurth, Ursula; Reitner, Andreas

2013-07-01

Automated detection of subtle changes in peripapillary retinal nerve fibre layer thickness (RNFLT) over time using optical coherence tomography (OCT) is limited by inherent image quality before layer segmentation, stabilization of the scan on the peripapillary retina and its precise placement on repeated scans. The present study evaluates image quality and reproducibility of spectral domain (SD)-OCT comparing different rates of automatic real-time tracking (ART). Peripapillary RNFLT was measured in 40 healthy eyes on six different days using SD-OCT with an eye-tracking system. Image brightness of OCT with unaveraged single frame B-scans was compared to images using ART of 16 B-scans and 100 averaged frames. Short-term and day-to-day reproducibility was evaluated by calculation of intraindividual coefficients of variation (CV) and intraclass correlation coefficients (ICC) for single measurements as well as for seven repeated measurements per study day. Image brightness, short-term reproducibility, and day-to-day reproducibility were significantly improved using ART of 100 frames compared to one and 16 frames. Short-term CV was reduced from 0.94 ± 0.31 % and 0.91 ± 0.54 % in scans of one and 16 frames to 0.56 ± 0.42 % in scans of 100 averaged frames (P ≤ 0.003 each). Day-to-day CV was reduced from 0.98 ± 0.86 % and 0.78 ± 0.56 % to 0.53 ± 0.43 % (P ≤ 0.022 each). The range of ICC was 0.94 to 0.99. Sample size calculations for detecting changes of RNFLT over time in the range of 2 to 5 μm were performed based on intraindividual variability. Image quality and reproducibility of mean peripapillary RNFLT measurements using SD-OCT is improved by averaging OCT images with eye-tracking compared to unaveraged single frame images. Further improvement is achieved by increasing the amount of frames per measurement, and by averaging values of repeated measurements per session. These strategies may allow a more accurate evaluation of RNFLT reduction in clinical trials observing optic nerve degeneration.

[Distal clavicle fracture].

PubMed

Seppel, G; Lenich, A; Imhoff, A B

2014-06-01

Reposition and fixation of unstable distal clavicle fractures with a low profile locking plate (Acumed, Hempshire, UK) in conjunction with a button/suture augmentation cerclage (DogBone/FibreTape, Arthrex, Naples, FL, USA). Unstable fractures of the distal clavicle (Jäger and Breitner IIA) in adults. Unstable fractures of the distal clavicle (Jäger and Breitner IV) in children. Distal clavicle fractures (Jäger and Breitner I, IIB or III) with marked dislocation, injury of nerves and vessels, or high functional demand. Patients in poor general condition. Fractures of the distal clavicle (Jäger and Breitner I, IIB or III) without marked dislocation or vertical instability. Local soft-tissue infection. Combination procedure: Initially the lateral part of the clavicle is exposed by a 4 cm skin incision. After reduction of the fracture, stabilization is performed with a low profile locking distal clavicle plate. Using a special guiding device, a transclavicular-transcoracoidal hole is drilled under arthroscopic view. Additional vertical stabilization is arthroscopically achieved by shuttling the DogBone/FibreTape cerclage from the lateral portal cranially through the clavicular plate. The two ends of the FibreTape cerclage are brought cranially via adjacent holes of the locking plate while the DogBone button is placed under the coracoid process. Thus, plate bridging is achieved. Finally reduction is performed and the cerclage is secured by surgical knotting. Use of an arm sling for 6 weeks. Due to the fact that the described technique is a relatively new procedure, long-term results are lacking. In the short term, patients postoperatively report high subjective satisfaction without persistent pain.

Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

PubMed

Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

2017-01-01

The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

The second report of a new hypomyelinating disease due to a defect in the VPS11 gene discloses a massive lysosomal involvement.

PubMed

Hörtnagel, Konstanze; Krägeloh-Mann, Inge; Bornemann, Antje; Döcker, Miriam; Biskup, Saskia; Mayrhofer, Heidi; Battke, Florian; du Bois, Gabriele; Harzer, Klaus

2016-11-01

Vesicular protein sorting-associated proteins (VPS, including VPS11) are indispensable in the endocytic network, in particular the endosome-lysosome biogenesis. Exome sequencing revealed the homozygous variant p.Leu387_ Gly395del in the VPS11 gene in two siblings. On immunoblotting, the mutant VPS11 protein showed a distinctly reduced immunostaining intensity. The children presented with primary and severe developmental delay associated with myoclonic seizures, spastic tetraplegia, trunk and neck hypotonia, blindness, hearing loss, and microcephaly. Neuro-imaging showed severe hypomyelination affecting cerebral and cerebellar white matter and corpus callosum, in the absence of a peripheral neuropathy. Electron microscopy of a skin biopsy revealed clusters of membranous cytoplasmic bodies in dermal unmyelinated nerve axons, and numbers of vacuoles in eccrine sweat glands, similar to what is seen in a classic lysosomal storage disease (LSD). Bone marrow cytology showed a high number of storage macrophages with a micro-vacuolated cytoplasm. Biochemically, changes in urinary glycosphingolipids were reminiscent of those in prosaposin deficiency (another LSD). The clinical and neuro-imaged features in our patients were almost identical to those in some recently reported patients with another variant in the VPS11 gene, p.Cys846Gly; underlining the presumed pathogenic potential of VPS11 defects. A new feature was the morphological evidence for lysosomal storage in VPS11 deficiency: This newly characterised disease can be viewed as belonging to the complex field of LSD.

Ionic mechanisms in peripheral pain.

PubMed

Fransén, Erik

2014-01-01

Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs. © 2014 Elsevier Inc. All rights reserved.

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

Selective control of small versus large diameter axons using infrared laser light (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lothet, Emilie H.; Shaw, Kendrick M.; Horn, Charles C.; Lu, Hui; Wang, Yves T.; Jansen, E. Duco; Chiel, Hillel J.; Jenkins, Michael W.

2016-03-01

Sensory information is conveyed to the central nervous system via small diameter unmyelinated fibers. In general, smaller diameter axons have slower conduction velocities. Selective control of such fibers could create new clinical treatments for chronic pain, nausea in response to chemo-therapeutic agents, or hypertension. Electrical stimulation can control axonal activity, but induced axonal current is proportional to cross-sectional area, so that large diameter fibers are affected first. Physiologically, however, synaptic inputs generally affect small diameter fibers before large diameter fibers (the size principle). A more physiological modality that first affected small diameter fibers could have fewer side effects (e.g., not recruiting motor axons). A novel mathematical analysis of the cable equation demonstrates that the minimum length along the axon for inducing block scales with the square root of axon diameter. This implies that the minimum length along an axon for inhibition will scale as the square root of axon diameter, so that lower radiant exposures of infrared light will selectively affect small diameter, slower conducting fibers before those of large diameter. This prediction was tested in identified neurons from the marine mollusk Aplysia californica. Radiant exposure to block a neuron with a slower conduction velocity (B43) was consistently lower than that needed to block a faster conduction velocity neuron (B3). Furthermore, in the vagus nerve of the musk shrew, lower radiant exposure blocked slow conducting fibers before blocking faster conducting fibers. Infrared light can selectively control smaller diameter fibers, suggesting many novel clinical treatments.

Transcallosal transfer of information and functional asymmetry of the human brain.

PubMed

Nowicka, Anna; Tacikowski, Pawel

2011-01-01

The corpus callosum is the largest commissure in the brain and acts as a "bridge" of nerve fibres connecting the two cerebral hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal communication and cooperation between the two hemispheres. Evolutionary pressures guiding brain size are accompanied by reduced interhemispheric and enhanced intrahemispheric connectivity. Some lines of evidence suggest that the speed of transcallosal conduction is limited in large brains (e.g., in humans), thus favouring intrahemispheric processing and brain lateralisation. Patterns of directional symmetry/asymmetry of transcallosal transfer time may be related to the degree of brain lateralisation. Neural network modelling and electrophysiological studies on interhemispheric transmission provide data supporting this supposition.

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

PubMed

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

2013-01-01

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

Postsynaptic P2X3-containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice.

PubMed

Vandenbeuch, Aurelie; Larson, Eric D; Anderson, Catherine B; Smith, Steven A; Ford, Anthony P; Finger, Thomas E; Kinnamon, Sue C

2015-03-01

Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca(2+) transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Calbindin-immunoreactive cells in the fish enteric nervous system.

PubMed

Olsson, Catharina

2011-01-20

Calbindin is present in a large proportion of the intrinsic primary afferent neurons (IPANs) in the mammalian gut. Little is known about either calbindin or IPANs in fish. In the present study, calbindin immunoreactivity was investigated in the enteric nervous system of the teleost shorthorn sculpin (Myoxocephalus scorpius). Calbindin-immunoreactive nerve cell bodies and nerve fibres were present in all the gut regions except the cardiac stomach. The highest proportion was found in the proximal intestine where calbindin-immunoreactive cells constituted 59±6% (N=3) of the total Hu C/D-immunoreactive myenteric nerve cell population. In other regions, calbindin-immunoreactive cells constituted around 30% of the total population. The cells were generally multipolar with one long axon. The size distribution differed significantly between calbindin-positive and calbindin-negative cells in each of the three animals examined. Calbindin-positive neurons in the proximal intestine had a mean cross-sectional soma area of 163±73μm(2) (n=183 cells) while calbindin-negative cells were 348±221μm(2) (n=127 cells). Calbindin immunoreactivity colocalised to a large extent with serotonin immunoreactivity, but not with choline acetyltransferase (ChAT)-immunoreactivity. Thus, the calbindin-immunoreactive nerve cell population in the shorthorn sculpin gut seems to constitute a homogenous subpopulation of the enteric neurons, at least when considering the size and content of some transmitters. Whether markers other than serotonin and ChAT would differentiate the population remains to be tested. In conclusion, the calbindin-immunoreactive cells in the sculpin differ from mammalian IPANs with regard to several parameters and future functional studies could hopefully add information about the role of this large group of cells in the fish enteric nervous system. Copyright © 2010 Elsevier B.V. All rights reserved.

Investigations of nerve populations influencing ion transport that can be stimulated electrically, by serotonin and by a nicotinic agonist.

PubMed

Keast, J R; Furness, J B; Costa, M

1985-11-01

It is known that the majority of the mucosal nerve fibres in the guinea-pig small intestine arise from submucous ganglia. There are a number of neurochemically distinct populations of nerve cells in these ganglia, approximately half of them being cholinergic. In these studies we have stimulated isolated preparations of mucosa and submucosa with electrical field stimulation (EFS), 5-hydroxytryptamine (5-HT) and the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) and monitored changes in ion transport. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (Isc) was measured as an indication of net ion transport across the tissue. EFS consisted of passing bipolar rectangular stimulus pulses through two platinum wires, one placed on each of the mucosal and submucosal sides of the tissue. EFS, 5-HT and DMPP each caused a transient increase in Isc. Tetrodotoxin (TTX) abolished all of the EFS response and the majority of the response observed with 5-HT or DMPP, suggesting that the action of these stimuli on the mucosa is primarily nerve-mediated. The TTX-sensitive responses to 5-HT (greater than 5 X 10(-7) M) and DMPP consisted of two components, appearing with different latencies. The response to EFS also consisted of two components. Hyoscine abolished the first component of each of these responses and significantly reduced the amplitude of the second, by 40% (for EFS and 5-HT) and 84% (for DMPP). At lower 5-HT concentrations, only the later component was seen, and this was unaffected by hyoscine.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

PubMed Central

Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

1992-01-01

1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

PubMed

Fatehi, M; Rowan, E G; Harvey, A L

2002-01-01

The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

The central projections of the laryngeal nerves in the rat

PubMed Central

Pascual-Font, Arán; Hernández-Morato, Ignacio; McHanwell, Stephen; Vázquez, Teresa; Maranillo, Eva; Sañudo, Jose; Valderrama-Canales, Francisco J

2011-01-01

The larynx serves respiratory, protective, and phonatory functions. The motor and sensory innervation to the larynx controlling these functions is provided by the superior laryngeal nerve (SLN) and the recurrent laryngeal nerve (RLN). Classical studies state that the SLN innervates the cricothyroid muscle and provides sensory innervation to the supraglottic cavity, whereas the RLN supplies motor innervation to the remaining intrinsic laryngeal muscles and sensory innervation to the infraglottic cavity, but recent data suggest a more complex anatomical and functional organisation. The current neuroanatomical tracing study was undertaken to provide a comprehensive description of the central brainstem connections of the axons within the SLN and the RLN, including those neurons that innervate the larynx. The study has been carried out in 41 adult male Sprague–Dawley rats. The central projections of the laryngeal nerves were labelled following application of biotinylated dextran amines onto the SLN, the RLN or both. The most remarkable result of the study is that in the rat the RLN does not contain any afferent axons from the larynx, in contrast to the pattern observed in many other species including man. The RLN supplied only special visceromotor innervation to the intrinsic muscles of the larynx from motoneurons in the nucleus ambiguus (Amb). All the afferent axons innervating the larynx are contained within the SLN, and reach the nucleus of the solitary tract. The SLN also contained secretomotor efferents originating from motoneurons in the dorsal motor nucleus of the vagus, and special visceral efferent fibres from the Amb. In conclusion, the present study shows that in the rat the innervation of the larynx differs in significant ways from that described in other species. PMID:21599662

Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats

PubMed Central

Kirkup, Anthony J; Jiang, Wen; Bunnett, Nigel W; Grundy, David

2003-01-01

Proteinase-activated receptor 2 (PAR2) is a receptor for mast cell tryptase and trypsins and might participate in brain-gut communication. However, evidence that PAR2 activation can lead to afferent impulse generation is lacking. To address this issue, we examined the sensitivity of jejunal afferent nerves to a hexapeptide agonist of PAR2, SLIGRL-NH2, and the modulation of the resulting response to treatment with drugs and vagotomy. Multiunit recordings of jejunal afferent activity were made using extracellular recording techniques in anaesthetised male rats. SLIGRL-NH2 (0.001–1 mg kg−1, I.V.) increased jejunal afferent firing and intrajejunal pressure. The reverse peptide sequence (1 mg kg−1, I.V.), which does not stimulate PAR2, was inactive. Naproxen (10 mg kg−1, I.V.), but not a cocktail of ω-conotoxins GVIA and SVIB (each at 25 μg kg−1, I.V.), curtailed both the afferent response and the intrajejunal pressure rise elicited by the PAR2 agonist. Although neither treatment modulated the peak magnitude of the afferent firing, they each altered the intestinal motor response, unmasking an initial inhibitory component. Nifedipine (1 mg kg−1, I.V.) reduced the peak magnitude of the afferent nerve discharge and abolished the initial rise in intrajejunal pressure produced by SLIGRL-NH2. Vagotomy did not significantly influence the magnitude of the afferent response to the PAR2 agonist, which involves a contribution from capsaicin-sensitive fibres. In conclusion, intravenous administration of SLIGRL-NH2 evokes complex activation of predominantly spinally projecting extrinsic intestinal afferent nerves, an effect that involves both direct and indirect mechanisms. PMID:14561839

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse

PubMed Central

Hossain-Ibrahim, Mohammed K; Rezajooi, Kia; Stallcup, William B; Lieberman, Alexander R; Anderson, Patrick N

2007-01-01

Background The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve. Results We studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST) axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC) axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion), most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice. Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG) cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses revealed significant differences between wild-type and knockout mice. Conclusion These findings show that NG2 is unlikely to be a major inhibitor of axonal regeneration after injury to the CNS, and, further, that NG2 is unlikely to be necessary for regeneration or functional recovery following peripheral nerve injury. PMID:17900358

Crayfish neuromuscular facilitation activated by constant presynaptic action potentials and depolarizing pulses

PubMed Central

Zucker, Robert S.

1974-01-01

1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres. 2. Apparent changes in n.t.p. are attributed to three causes. (i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation. (ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies. (iii) Some changes in n.t.p. are blocked by γ-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements. 3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval. 4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected. 5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses. 6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that of e.j.p.s evoked by nerve impulses. 7. It is concluded that facilitation in the crayfish claw opener is not due to a change in the presynaptic action potential, but is due to some change at a later step in the depolarization—secretion process. PMID:4153766

Crayfish neuromuscular facilitation activated by constant presynaptic action potentials and depolarizing pulses.

PubMed

Zucker, R S

1974-08-01

1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres.2. Apparent changes in n.t.p. are attributed to three causes.(i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation.(ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies.(iii) Some changes in n.t.p. are blocked by gamma-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements.3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval.4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected.5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses.6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that of e.j.p.s evoked by nerve impulses.7. It is concluded that facilitation in the crayfish claw opener is not due to a change in the presynaptic action potential, but is due to some change at a later step in the depolarization-secretion process.

Stimulation of sensory neuropeptide release by nociceptin/orphanin FQ leads to hyperaemia in acutely inflamed rat knees

PubMed Central

Zhang, Chunfen; McDougall, Jason J

2006-01-01

The peripheral effect of the ‘opioid-like' peptide nociceptin/orphanin FQ (N/OFQ) on joint blood flow was investigated in acutely inflamed rats. Sensory neuropeptide release from capsaicin-sensitive nerves and the involvement of synovial mast cells and leukocytes on these vasomotor responses were also studied. Blood flow measurements of exposed knee joints were performed in urethane-anaesthetised rats (2 mg kg−1 intraperitoneal) using laser Doppler perfusion imaging. Topical administration of N/OFQ (10−13–10−8 mol) to acutely inflamed joints caused a dose-dependent increase in synovial perfusion with an ED50 of 4.0 × 10−10 mol. This vasodilatatory response was blocked by the selective NOP receptor antagonist [Phe1-(CH2-NH)-Gly2]-Nociceptin(1–13)-NH2 (10−9 mol) (P<0.0001). Co-administration of N/OFQ with the neurokinin-1 (NK1) receptor antagonist [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P (10−12 mol), the vasoactive intestinal peptide (VIP) receptor antagonist VIP6–28 (10−9 mol) or the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP8–37 (10−9 mol) all blocked the hyperaemic effect of N/OFQ (P<0.0001). Treatment of acutely inflamed knees with capsaicin (8-methyl-N-vanillyl-6-noneamide) to destroy unmyelinated joint afferents also inhibited N/OFQ vasomotor activity. Stabilisation of synovial mast cells with disodium cromoglycate (cromolyn) ameliorated N/OFQ responses, whereas inactivation of circulating leukocytes with the pan-selectin inhibitor fucoidin completely blocked N/OFQ-induced hyperaemia in these joints. These experiments show that in acutely inflamed knee joints, N/OFQ acts on NOP receptors located on synovial mast cells and leukocytes leading to the secondary release of proinflammatory mediators into the joint. These agents subsequently stimulate sensory neuropeptide release from capsaicin-sensitive nerves culminating in vasodilatation and increased articular blood flow. PMID:16783411

Glutamate-induced excitation and sensitization of nociceptors in rat glabrous skin.

PubMed

Du, J; Koltzenburg, M; Carlton, S M

2001-01-01

Anatomical studies demonstrate the presence of glutamate receptors on unmyelinated axons in peripheral cutaneous nerves. Pharmacological studies show that intraplantar injection of glutamate or glutamate agonists in the glabrous skin results in nociceptive behaviors. The present study describes a novel in vitro skin-nerve preparation using the glabrous skin from the rat hindpaw. In the first series of experiments, recordings were obtained from 141 fibers that responded to a strong mechanical search stimulus. Based on their conduction velocity they were classified as C (27%), A delta (28%) and A beta (45%) fibers. The C and A delta fibers typically exhibited sustained firing during suprathreshold mechanical stimuli whereas both rapidly (66%) and slowly (34%) adapting responses were obtained from A beta fibers. Noxious heat excited 46% of the C fibers but only 12% of the A delta units. In another series of experiments application of an ascending series of glutamate concentrations (10, 100, 300, and 1000 microM) to A delta (n=14) and C (n=19) nociceptors resulted in a significant excitation of 43% (6/14) A delta fibers and 68% (13/19) C fibers. At these concentrations, there was no excitation of A beta units (n=13). Superfusion of the receptive fields of either mechanoheat-sensitive A (AMH, n=10) or C fibers (CMH, n=12) for 2 min with 300 microM glutamate resulted in sensitization of 90% (9/10) AMH and 92% (11/12) CMH fibers to subsequent thermal stimulation. This was evidenced by a significant (1) decrease in thermal threshold for activation, (2) increase in discharge rate, and (3) increase in peak instantaneous frequencies during the second heat trial. Glutamate-induced sensitization to heat occurred in the absence of either a glutamate-induced excitation or an initial heat response. Exposure of A delta or C fibers to glutamate did not result in a decrease in von Frey thresholds. These data provide a physiological basis for the nociceptive behaviors that arise following intraplantar injection of glutamate or glutamate agonists. Furthermore, demonstration of glutamate-induced excitation and heat sensitization of nociceptors indicates that local or topical administration of glutamate receptor antagonists may have therapeutic potential for the treatment of pain.

The retinal nerve fibre layer thickness in glaucomatous hydrophthalmic eyes assessed by scanning laser polarimetry with variable corneal compensation in comparison with age-matched healthy children.

PubMed

Hložánek, Martin; Ošmera, Jakub; Ležatková, Pavlína; Sedláčková, Petra; Filouš, Aleš

2012-12-01

To compare the thickness of the retinal nerve fibre layer (RNFL) in hydrophthalmic glaucomatous eyes in children with age-matched healthy controls using scanning laser polarimetry with variable corneal compensation (GDxVCC). Twenty hydrophthalmic eyes of 20 patients with the mean age of 10.64 ± 3.02 years being treated for congenital or infantile glaucoma were included in the analysis. Evaluation of RNFL thickness measured by GDxVCC in standard Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) parameters was performed. The results were compared to TSNIT values of an age-matched control group of 120 healthy children published recently as referential values. The correlation between horizontal corneal diameter and RNFL thickness in hydrophthalmic eyes was also investigated. The mean ± SD values in TSNIT Average, Superior Average, Inferior Average and TSNIT SD in hydrophthalmic eyes were 52.3 ± 11.4, 59.7 ± 17.1, 62.0 ± 15.6 and 20.0 ± 7.8 μm, respectively. All these values were significantly lower compared to referential TSNIT parameters of age-matched healthy eyes (p = 0.021, p = 0.001, p = 0.003 and p = 0.018, respectively). A substantial number of hydrophthalmic eyes laid below the level of 5% probability of normality in respective TSNIT parameters: 30% of the eyes in TSNIT average, 50% of the eyes in superior average, 30% of the eyes in inferior average and 45% of the eyes in TSNIT SD. No significant correlation between enlarged corneal diameter and RNFL thickness was found. The mean values of all standard TSNIT parameters assessed using GDxVCC in hydrophthalmic glaucomatous eyes in children were significantly lower in comparison with referential values of healthy age-matched children. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Neuronal regeneration in the newt: a model to study the partly reconstruction of the neural tissue in real and simulated weightles sness

NASA Astrophysics Data System (ADS)

Anton, H.; Grigoryan, E.; Mitashov, V.

The micro -"g" effect on nervous tissue regeneration in newts has been investigated by our group for many years. It has been performed in real and in simulated microgravity with a clinostat. During limb regeneration the motor - and sensory nerves regrow perfectly within the newly formed limb. Like in `1g' conditions they are responsible for the initiation of blastema formation and continuity of g owth andr differentiation. Except for a general acceleration of growth and differentiation processes no differences became visible. Tail regeneration, which is perfectly regulated in newts during their whole life, includes the restoration of the spinal cord and dorsal root ganglia. They follow or initiate an accelerated growth. Up to the present the cellular derivation of the sensory neurones within the regenerate has not yet been clarified. But growth acceleration comprises the whole nervous system. That means a totally new formation of the sensory connection from the periphery to the whole spinal cord. Regeneration must be initiated by the outgrowth of nerve fibres into the wound area. This may be performed by the remaining cut sensory fibres of the last stump segment and should be followed by the differentiation of undifferentiated cells of neural crest origin nearby the amputation area. Such cells are present in the form of meningeal cells which are the origin of mantle and Schwann cells too. Corresponding to the well proved growth acceleration of lens, retina, connective tissue, muscle and skin, the real and simulated microgravity affects the nervous system in the same manner. Tissues and organs of adult organisms have no chance to remain unaffected by the microgravity effect. We try to find the trigger which initiates the accelerated proliferation of the stem cells of sensory neurons, mantle and sheath cells under micro-"g" conditions.

Mechanisms defining the electrotonic potential abnormalities in simulated amyotrophic lateral sclerosis.

PubMed

Stephanova, D I; Krustev, S M; Negrev, N

2012-06-01

Electrotonic potentials allow the accommodative processes to polarizing stimuli to be assessed. Electrotonic potential transients in response to applied polarizing stimuli are caused by the kinetics of underlying axonal conductances. Here, we study these transients using our multi-layered model of the human motor nerve, in three simulated cases of the motor neuron disease amyotrophic lateral sclerosis (ALS): ALS1, ALS2 and ALS3 are three consecutively greater degrees of uniform axonal dysfunctions along the human motor nerve fibre. The results show that the responses in the ALS1 case are quite similar to the normal case. In contrast, in the ALS2 and ALS3 cases, long-lasting (100 ms) subthreshold depolarizing stimuli activate the classical "transient" Na(+) channels in the nodal and in the internodal axolemma beneath the myelin sheath; this leads to action potential generation during the early parts of the electrotonic responses in all compartments along the fibre length. The results also show that the electrotonic potentials in response to long-lasting (100 ms) subthreshold hyperpolarizing stimuli in the ALS1 and ALS2 cases are quiet similar to those of the normal case. However, the current kinetics in the ALS3 case differs from the normal case after the termination of the long-lasting hyperpolarizing stimuli. In the most abnormal ALS3 case, the activation of the Na(+) channels in the nodal and in the internodal axolemma leads to repetitive action potential generation in the late parts (100-200 ms) of the hyperpolarizing electrotonic responses. The results show that the repetitive firing, due to the progressively increased nodal and internodal ion channel dysfunction, are consistent with the loss of functional potassium channels involving both the fast and the slow potassium channel types. The results confirm that the electrotonic potentials in the three simulated ALS cases are specific indicators for the motor neuron disease ALS. The mechanisms underlying the simulated ALS are also discussed.

Response characteristics of periodontal mechanoreceptors to mechanical stimulation of canine and incisor teeth in the cat.

PubMed

Tabata, T; Suzuki, T; Watanabe, M

1995-09-01

The alveolar bone that overlies the labial aspect of the root of the right lower canine tooth was pared down until paper thin. Thirty-five periodontal mechanosensitive (PM) units sensitive to stimulation of the canine and incisor and to punctate stimulation through the thinned bone of the periodontal ligament of the canine were recorded from the inferior alveolar nerve rostral to the masseter muscle. The units showed a sustained and directionally selective response to pressure applied to the teeth. The optimal directions of stimulation for each tooth in the receptive field were parallel and oriented linguolabially. When the canine was stimulated mechanically in the optimal stimulus direction, the interspike intervals of the responses were relatively regular in most PM units (91%). The conditioning and test stimuli were applied to the adjacent canine and third incisor. The conditioning stimulus (0.10 N) was given to one of these teeth in the optimal stimulus direction. The test stimulus (0.02 N or 0.05 N) was applied to the adjacent tooth in the opposite direction in order to examine the effect of mechanical spreading of the conditioning stimulus on the adjacent tooth. In most PM units, the spike discharges evoked by the conditioning stimulus given to the incisor were stopped by the test stimulus given to the canine. When the given stimuli were reversed, the firings evoked by the conditioning stimulus were slightly depressed by the test stimulus. After removing the spot-like PM receptor site(s) in the paper-thin area of bone, all units but one did not respond to stimulation. These results provide evidence that neurones with multiple-tooth receptive fields and regular spike-interval responses recorded from the inferior alveolar nerve come from the mechanical spreading effect of the stimulation of one tooth on an adjacent tooth through the trans-septal fibre system and that neurones with irregular-interval responses are due to the ramification of PM fibres peripherally.

Cardiac troponin T and fast skeletal muscle denervation in ageing.

PubMed

Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong-Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian-Ping; Delbono, Osvaldo; Zhang, Tan

2017-10-01

Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii) decreased the levels of gene expression of muscle denervation markers; and (iii) enhanced neurotransmission efficiency at NMJ. Cardiac troponin T at the NMJ region contributes to NMJ functional decline with ageing mainly in the fast-twitch skeletal muscle through interfering with PKA signalling. This knowledge could inform useful targets for prevention and therapy of age-related decline in muscle function. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Benefit-risk assessment of ropivacaine in the management of postoperative pain.

PubMed

Zink, Wolfgang; Graf, Bernhard M

2004-01-01

Ropivacaine is a long-acting amide-type local anaesthetic, released for clinical use in 1996. In comparison with bupivacaine, ropivacaine is equally effective for subcutaneous infiltration, epidural and peripheral nerve block for surgery, obstetric procedures and postoperative analgesia. Nevertheless, ropivacaine differs from bupivacaine in several aspects: firstly, it is marketed as a pure S(-)-enantiomer and not as a racemate, and secondly, its lipid solubility is markedly lower. These features have been suggested to significantly improve the safety profile of ropivacaine, and indeed, numerous studies have shown that ropivacaine has less cardiovascular and CNS toxicity than racemic bupivacaine in healthy volunteers. Extensive clinical data have demonstrated that epidural 0.2% ropivacaine is nearly identical to 0.2% bupivacaine with regard to onset, quality and duration of sensory blockade for initiation and maintenance of labour analgesia. Ropivacaine also provides effective pain relief after abdominal or orthopaedic surgery, especially when given in conjunction with opioids or other adjuvants. Nevertheless, epidurally administered ropivacaine causes significantly less motor blockade at low concentrations. Whether the greater degree of blockade of nerve fibres involved in pain transmission (Adelta- and C-fibres) than of those controlling motor function (Aalpha- and Abeta-fibres) is due to a lower relative potency compared with bupivacaine or whether other physicochemical properties or stereoselectivity are involved, is still a matter of intense debate. Recommended epidural doses for postoperative or labour pain are 20-40 mg as bolus with 20-30 mg as top-up dose, with an interval of >or=30 minutes. Alternatively, 0.2% ropivacaine can be given as continuous epidural infusion at a rate of 6-14 mL/h (lumbar route) or 4-10 mL/h (thoracic route). Preoperative or postoperative subcutaneous wound infiltration, during cholecystectomy or inguinal hernia repair, with ropivacaine 100-175 mg has been shown to be more effective than placebo and as effective as bupivacaine in reducing wound pain, whereby the vasoconstrictive potency of ropivacaine may be involved. Similar results were found in peripheral blockades on upper and lower limbs. Ropivacaine shows an identical efficacy and potency to that of bupivacaine, with similar analgesic duration over hours using single shot or continuous catheter techniques. In summary, ropivacaine, a newer long-acting local anaesthetic, has an efficacy generally similar to that of the same dose of bupivacaine with regard to postoperative pain relief, but causes less motor blockade and stronger vasoconstriction at low concentrations. Despite a significantly better safety profile of the pure S(-)-isomer of ropivacaine, the increased cost of ropivacaine may presently limit its clinical utility in postoperative pain therapy.

Twitch analysis as an approach to motor unit activation during electrical stimulation.

PubMed

Heyters, M; Carpentier, A; Duchateau, J; Hainaut, K

1994-12-01

The mechanical twitch in response to increasing electrical stimulus intensity, delivered both over the motor point and motor nerve, was recorded in the first dorsal interosseous (FDI) and the adductor pollicis (AP), and only over the motor point in the soleus (Sol), lateral (LG), and medial (MG) gastrocnemius muscles of human subjects. The relationship between intensity of electrical stimulation (ES) and twitch torque showed a positive linear regression in all muscles. In the FDI and AP the relationship was not significantly different when ES was applied at the motor point or over the motor nerve. At small intensities of activation, ES induced larger twitch torques in the MG and LG, which contain a roughly equal proportion of slow and fast motor units (MUs) compared to the Sol, which is composed mainly of slow type fibres. Moreover, the relationship between ES intensity and twitch time-to-peak is best fitted in all muscles by a power curve that shows a greater twitch time-to-peak range in its initial part for muscles containing a larger proportion of fast MUs (LG, MG) than for muscles mainly composed of slow MUs (Sol). In conclusion, these results induced by ES at the motor point and/or over the motor nerve confirm the concept of a reversed sequence of MU activation, as compared to voluntary contractions, and document this viewpoint in muscles of different function and composition. The reversed sequence of MU activation is more clearly evident during motor point ES.

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

PubMed

Nakano, Tomonori; Kurimoto, Shigeru; Kato, Shuichi; Asano, Kenichi; Hirata, Takuma; Kiyama, Hiroshi; Hirata, Hitoshi

2018-06-01

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 μm 2 , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle. Copyright © 2018 John Wiley & Sons, Ltd.

Gelatin-based hydrogel for vascular endothelial growth factor release in peripheral nerve tissue engineering.

PubMed

Gnavi, S; di Blasio, L; Tonda-Turo, C; Mancardi, A; Primo, L; Ciardelli, G; Gambarotta, G; Geuna, S; Perroteau, I

2017-02-01

Hydrogels are promising materials in regenerative medicine applications, due to their hydrophilicity, biocompatibility and capacity to release drugs and growth factors in a controlled manner. In this study, biocompatible and biodegradable hydrogels based on blends of natural polymers were used in in vitro and ex vivo experiments as a tool for VEGF-controlled release to accelerate the nerve regeneration process. Among different candidates, the angiogenic factor VEGF was selected, since angiogenesis has been long recognized as an important and necessary step during tissue repair. Recent studies have pointed out that VEGF has a beneficial effect on motor neuron survival and Schwann cell vitality and proliferation. Moreover, VEGF administration can sustain and enhance the growth of regenerating peripheral nerve fibres. The hydrogel preparation process was optimized to allow functional incorporation of VEGF, while preventing its degradation and denaturation. VEGF release was quantified through ELISA assay, whereas released VEGF bioactivity was validated in human umbilical vein endothelial cells (HUVECs) and in a Schwann cell line (RT4-D6P2T) by assessing VEGFR-2 and downstream effectors Akt and Erk1/2 phosphorylation. Moreover, dorsal root ganglia explants cultured on VEGF-releasing hydrogels displayed increased neurite outgrowth, providing confirmation that released VEGF maintained its effect, as also confirmed in a tubulogenesis assay. In conclusion, a gelatin-based hydrogel system for bioactive VEGF delivery was developed and characterized for its applicability in neural tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle.

PubMed Central

O'Brien, R A; Ostberg, A J; Vrbová, G

1978-01-01

1. The mechanism responsible for the elimination of polyneuronal innervation in developing rat soleus muscles was studied electrophysiologically and histologically. 2. Initially all the axons contacting a single end-plate have simple bulbous terminals. As elimination proceeds one axon develops terminal branches while the other terminals remain bulbous and may be seen in contact with, or a short distance away from, the end-plate. It is suggested that the branched terminal remains in contact with the muscle fibre while the other terminals withdraw. 3. At a time when polyneuronal innervation can no longer be detected electrophysiologically, the histological technique still shows the presence of end-plates contacted by more than one nerve terminal. 4. The effect of activity on the disappearance of polyneuronal innervation was examined. Activity was increased by electrical stimulation of the right sciatic nerve. This procedure also produced reflex activity in the contralateral limb. In both cases polyneuronal innervation was eliminated more rapidly in the active muscles. 5. The finding that proteolytic enzymes are released from muscles treated with acetylcholine (ACh), and the observation of the more rapid elimination of supernumerary terminals at the end-plates of active muscles, lead to the suggestion that superfluous nerve-muscle contacts are removed by the proteolytic enzymes in response to neuromuscular activity. The selective stabilization of only one of the terminals is discussed in the light of these results. Images Plate 1 Plate 2 PMID:722562

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

PubMed

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

2014-08-01

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

The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis.

PubMed

Eliav, Eli; Benoliel, Rafael; Herzberg, Uri; Kalladka, Mythili; Tal, Michael

2009-05-01

Inflammation along a nerve trunk (perineural inflammation), without detectable axonal damage, has been shown to induce transient pain in the organ supplied by the nerve. The aims of the present study were to study the role IL-6 and IL-1beta, in pain induced by perineural inflammation. IL-6 and IL-1beta secretion from rat's sciatic nerves, L-5 Dorsal Root Ganglia (DRG), and the hind paw skin, 3 and 8 days following exposure of the nerve to Complete Freund's Adjuvant (CFA), were measured using ELISA method. Hind paw tactile-allodynia, mechano-hyperalgesia, heat-allodynia and electrical detection thresholds were tested up to 8 days following the application of CFA, IL-6 or IL-1beta adjacent to the sciatic nerve trunk. Employing electrophysiological recording, saphenous nerve spontaneous activity, nerve trunk mechano-sensitivity and paw tactile detection threshold (determined by recording action potential induced by the lowest mechanical stimulus) were assessed 3 and 8 days following exposure of the nerve trunk to CFA, IL-6, or IL-1beta. IL-6 and IL-1beta secretion from the nerve was significantly elevated on the 3rd day post-operation (DPO). On the 8th DPO, IL-6 levels returned to baseline while IL-1beta levels remained significantly elevated. The DRG cytokine's level was increased on the 3rd and 8th DPOs, contralateral cytokine's level was increased on the 3rd DPO. The skin IL-6 level was increased bilaterally on the 3rd DPO and returned to baseline on the 8th DPO. IL-1beta levels increased in the affected side on the 3rd and bilaterally on the 8th DPO. Direct application of IL-6 or CFA on the sciatic nerve induced significant hind paw tactile-allodynia from the 1st to 5th DPOs, reduced electrical detection threshold from the 1st to 3rd DPOs, mechano-hyperalgesia from 3rd to 5th DPOs and heat-allodynia on the 3rd DPO. Direct application of IL-1beta induced paw tactile and heat-allodynia on the 7-8th DPOs and mechano-hyperalgesia on the 5-8th DPOs. Perineural inflammation significantly increased spontaneous activity myelinated fibres 3 and 8 days following the application. Direct application of IL-6 induced elevation of spontaneous activity on the 3rd while IL-1beta on the 8th DPO. Nerve mechano-sensitivity was significantly increased on the 3rd day following exposure to CFA and IL-6 and on the 8th following CFA application. The rat's paw lowest mechanical force necessary for induction of action potential, was significantly reduced 3 days following CFA application. IL-6 and IL-1beta play an important role in pain induced by perineural inflammation. IL-6 activity is more prominent immediately following application (2-5th DPOs), while IL-1beta, activity is more significant in a later stage (5-8th DPOs).

Electroacupuncture at LI11 promotes jejunal motility via the parasympathetic pathway.

PubMed

Hu, Xuanming; Yuan, Mengqian; Yin, Yin; Wang, Yidan; Li, Yuqin; Zhang, Na; Sun, Xueyi; Yu, Zhi; Xu, Bin

2017-06-21

Gastrointestinal motility disorder has been demonstrated to be regulated by acupuncture treatment. The mechanisms underlying the effects of acupuncture stimulation of abdominal and lower limb acupoints on gastrointestinal motility have been thoroughly studied; however, the physiology underlying the effects of acupuncture on the forelimbs to mediate gastrointestinal motility requires further exploration. The aim of this study was to determine whether electroacupuncture (EA) at LI11 promotes jejunal motility, whether the parasympathetic pathway participates in this effect, and if so, which somatic afferent nerve fibres are involved. A manometric balloon was used to observe jejunal motility. The effects and mechanisms of EA at LI11 were explored in male Sprague-Dawley rats with or without drug administration (propranolol, clenbuterol, acetylcholine, and atropine) and with or without vagotomy. Three types of male mice (β 1 β 2 receptor-knockout [β 1 β 2 -/- ] mice, M 2 M 3 receptor-knockout [M 2 M 3 -/- ] mice and wild-type [WT] mice) were also studied by using different EA intensities (1, 2, 4, 6, and 8 mA). A total of 72 rats and 56 mice were included in the study. EA at LI11 increased the contractile amplitude of jejunal motility in the majority of both rats and mice. However, EA at LI11 did not enhance jejunal motility in rats administered atropine, rats that underwent vagotomy, and M 2 M 3 -‍‍/- mice (at all intensities). In WT mice, EA at LI11 significantly increased jejunal motility at all intensities except 1 mA, and a plateau was reached at intensities greater than 4 mA. Our results suggest that EA at LI11 promotes jejunal motility primarily by exciting the parasympathetic pathway, and that Aδ-fibres and C-fibres may play important roles in the process.

Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

PubMed Central

Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin

2014-01-01

Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567

Mechanisms of pain in distal symmetric polyneuropathy: a combined clinical and neurophysiological study.

PubMed

Truini, A; Biasiotta, A; La Cesa, S; Di Stefano, G; Galeotti, F; Petrucci, M T; Inghilleri, M; Cartoni, C; Pergolini, M; Cruccu, G

2010-09-01

In patients with distal symmetric polyneuropathy we assessed non-nociceptive Abeta- and nociceptive Adelta-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess Abeta-fibre function, and laser-evoked potentials (LEPs) to assess Adelta-fibre function. Patients with pain had the same age (P>0.50), but a longer delay since symptom onset than those without (P<0.01). Whereas the LEP amplitude was significantly lower in patients with pain than in those without (P<0.0001), NCS data did not differ between groups (P>0.50). LEPs were more severely affected in patients with ongoing pain than in those with provoked pain (P<0.0001). Our findings indicate that the impairment of Abeta-fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds. Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

An immunohistochemical study of the gut neuroendocrine system in juvenile pejerrey Odontesthes bonariensis (Valenciennes).

PubMed

Vigliano, F A; Muñoz, L; Hernández, D; Cerutti, P; Bermúdez, R; Quiroga, M I

2011-03-01

In this study, several neuropeptides were identified by immunohistochemistry in neuroendocrine cells (NEC) located in the gut epithelium and nerve cell bodies of the enteric nervous system of pejerrey Odontesthes bonariensis, a species that is a promising candidate for intensive aquaculture. The neuropeptides involved in orexigenic or anorexigenic action, i.e. gastrin, cholecystokinin-8, neuropeptide Y and calcitonin gene-related peptide (CGRP), displayed a significantly higher number of immunoreactive NECs in the anterior intestine, suggesting that this region of the gut plays an important role in the peripheral control of food intake. On the other hand, leu-enkephalin and vasoactive intestinal peptide (VIP), both associated with the modulation of the enteric immune system, showed no significant variations in the mean value of immunopositive NECs between the anterior and posterior intestine. This may indicate that their activity is required at a similar level along the entire gut. In addition, CGRP and VIP-immunoreactive neurons and nerve fibres were observed in the myenteric plexus, which might exert synergistic effects with the neuropeptides immunolocalized in NECs. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients.

PubMed

Garcia-Martin, E; Pueyo, V; Ara, J R; Almarcegui, C; Martin, J; Pablo, L; Dolz, I; Sancho, E; Fernandez, F J

2011-07-01

The objective of this research was to study the effect of optic neuritis (ON) on axonal damage in multiple sclerosis (MS) patients. Specifically, we compared changes over 2 years in the retinal nerve fibre layer (RNFL) between affected and contralateral eyes in MS patients with a prior history of ON. Thirty-four patients with one unilateral definitive episode of ON were included and underwent a complete ophthalmic examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials (VEP) and pattern electroretinogram (pERG). All patients were re-evaluated at 12 and 24 months. Parameters were compared between ON-affected and contralateral eyes in an initial exploration and over the course of the follow-up. Correlations between parameter changes were analysed. RNFL thickness and functional parameters showed more affection in ON eyes (p ≤ 0.05), but changes in measurements during the study were similar between both groups of eyes. Progressive axonal loss can be detected in the optic nerve, but ON is not a risk factor for increased chronic damage in MS patients without ophthalmic relapses. Loss of the RNFL is caused by progressive degeneration associated with the disease.

Palisade endings in extraocular eye muscles revealed by SNAP-25 immunoreactivity.

PubMed

Eberhorn, Andreas C; Horn, Anja K E; Eberhorn, Nicola; Fischer, Petra; Boergen, Klaus-Peter; Büttner-Ennever, Jean A

2005-03-01

Palisade endings form a cuff of nerve terminals around the tip of muscle fibres. They are found only in extraocular muscles, but no definite evidence for their role in eye movements has been established. Palisade endings have been reported in all species so far investigated except the rat. In this study we demonstrate that antibodies against SNAP-25, the synaptosomal associated protein of 25 kDa, reliably visualize the complete motor, sensory and autonomic innervation of the extraocular muscles in human, monkey and rat. The SNAP-25 antibody can be combined with other immunofluorescence procedures, and is used here to study properties of palisade endings. With SNAP-25 immunolabelling putative palisade endings are identified in the rat for the first time. They are not well branched, but fulfil several criteria of palisade endings, being associated with non-twitch fibres as shown by double labelling with 'myosin heavy chain slow-twitch' antibodies. The putative palisade endings of the rat lack alpha-bungarotoxin binding, which implies that these synapses are sensory. If palisade endings are sensory then they could function as an eye muscle proprioceptor. They seem to be a general feature of all vertebrate eye muscles, unlike the other two extraocular proprioceptors, muscle spindles and Golgi tendon organs, the presence of which varies widely between species.

Palisade endings in extraocular eye muscles revealed by SNAP-25 immunoreactivity

PubMed Central

Eberhorn, Andreas C; Horn, Anja KE; Eberhorn, Nicola; Fischer, Petra; Boergen, Klaus-Peter; Büttner-Ennever, Jean A

2005-01-01

Palisade endings form a cuff of nerve terminals around the tip of muscle fibres. They are found only in extraocular muscles, but no definite evidence for their role in eye movements has been established. Palisade endings have been reported in all species so far investigated except the rat. In this study we demonstrate that antibodies against SNAP-25, the synaptosomal associated protein of 25 kDa, reliably visualize the complete motor, sensory and autonomic innervation of the extraocular muscles in human, monkey and rat. The SNAP-25 antibody can be combined with other immunofluorescence procedures, and is used here to study properties of palisade endings. With SNAP-25 immunolabelling putative palisade endings are identified in the rat for the first time. They are not well branched, but fulfil several criteria of palisade endings, being associated with non-twitch fibres as shown by double labelling with ‘myosin heavy chain slow-twitch’ antibodies. The putative palisade endings of the rat lack α-bungarotoxin binding, which implies that these synapses are sensory. If palisade endings are sensory then they could function as an eye muscle proprioceptor. They seem to be a general feature of all vertebrate eye muscles, unlike the other two extraocular proprioceptors, muscle spindles and Golgi tendon organs, the presence of which varies widely between species. PMID:15733303

Mechanisms underlying the temporal precision of sound coding at the inner hair cell ribbon synapse

PubMed Central

Moser, Tobias; Neef, Andreas; Khimich, Darina

2006-01-01

Our auditory system is capable of perceiving the azimuthal location of a low frequency sound source with a precision of a few degrees. This requires the auditory system to detect time differences in sound arrival between the two ears down to tens of microseconds. The detection of these interaural time differences relies on network computation by auditory brainstem neurons sharpening the temporal precision of the afferent signals. Nevertheless, the system requires the hair cell synapse to encode sound with the highest possible temporal acuity. In mammals, each auditory nerve fibre receives input from only one inner hair cell (IHC) synapse. Hence, this single synapse determines the temporal precision of the fibre. As if this was not enough of a challenge, the auditory system is also capable of maintaining such high temporal fidelity with acoustic signals that vary greatly in their intensity. Recent research has started to uncover the cellular basis of sound coding. Functional and structural descriptions of synaptic vesicle pools and estimates for the number of Ca2+ channels at the ribbon synapse have been obtained, as have insights into how the receptor potential couples to the release of synaptic vesicles. Here, we review current concepts about the mechanisms that control the timing of transmitter release in inner hair cells of the cochlea. PMID:16901948

Blockade of Nogo Receptor Ligands Promotes Functional Regeneration of Sensory Axons After Dorsal Root Crush

PubMed Central

Harvey, Pamela A.; Lee, Daniel H.S.; Qian, Fang; Weinreb, Paul H.; Frank, Eric

2010-01-01

A major impediment for regeneration of axons within the central nervous system is the presence of multiple inhibitory factors associated with myelin. Three of these factors bind to the Nogo receptor, NgR, which is expressed on axons. Administration of exogenous blockers of NgR or NgR ligands promotes the regeneration of descending axonal projections after spinal cord hemisection. A more detailed analysis of CNS regeneration can be made by examining the growth of specific classes of sensory axons into the spinal cord after dorsal root crush injury . In this study, we assessed whether administration of a soluble peptide fragment of the NgR that binds to and blocks all three NgR ligands can promote regeneration after brachial dorsal root crush in adult rats. Intraventricular infusion of sNgR for one month results in extensive regrowth of myelinated sensory axons into the white and gray matter of the dorsal spinal cord, but unmyelinated sensory afferents do not regenerate. In concert with the anatomical growth of sensory axons into the cord, there is a gradual restoration of synaptic function in the denervated region, as revealed by extracellular microelectrode recordings from the spinal gray matter in response to stimulation of peripheral nerves. These positive synaptic responses are correlated with substantial improvements in use of the forelimb, as assessed by paw preference, paw withdrawal to tactile stimuli and the ability to grasp. These results suggest that sNgR may be a potential therapy for restoring sensory function following injuries to sensory roots. PMID:19439606

A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.

PubMed

de Carvalho Barbosa, Mariana; Kosturakis, Alyssa K; Eng, Cathy; Wendelschafer-Crabb, Gwen; Kennedy, William R; Simone, Donald A; Wang, Xin S; Cleeland, Charles S; Dougherty, Patrick M

2014-11-01

Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. ©2014 American Association for Cancer Research.

Morphology of the ampullae of Lorenzini in juvenile freshwater Carcharhinus leucas.

PubMed

Whitehead, Darryl L; Gauthier, Arnault R G; Mu, Erica W H; Bennett, Mike B; Tibbetts, Ian R

2015-05-01

Ampullae of Lorenzini were examined from juvenile Carcharhinus leucas (831-1,045 mm total length) captured from freshwater regions of the Brisbane River. The ampullary organ structure differs from all other previously described ampullae in the canal wall structure, the general shape of the ampullary canal, and the apically nucleated supportive cells. Ampullary pores of 140-205 µm in diameter are distributed over the surface of the head region with 2,681 and 2,913 pores present in two sharks that were studied in detail. The primary variation of the ampullary organs appears in the canal epithelial cells which occur as either flattened squamous epithelial cells or a second form of pseudostratified contour-ridged epithelial cells; both cell types appear to release material into the ampullary lumen. Secondarily, this ampullary canal varies due to involuted walls that form a clover-like canal wall structure. At the proximal end of the canal, contour-ridged cells abut a narrow region of cuboidal epithelial cells that verge on the constant, six alveolar sacs of the ampulla. The alveolar sacs contain numerous receptor and supportive cells bound by tight junctions and desmosomes. Pear-shaped receptor cells that possess a single apical kinocilium are connected basally by unmyelinated neural boutons. Opposed to previously described ampullae of Lorenzini, the supportive cells have an apical nucleus, possess a low number of microvilli, and form a unique, jagged alveolar wall. A centrally positioned centrum cap of cuboidal epithelial cells overlies a primary afferent lateral line nerve. © 2014 Wiley Periodicals, Inc.

Augmentation of partially regenerated nerves by end-to-side side-to-side grafting neurotization: experience based on eight late obstetric brachial plexus cases

PubMed Central

2006-01-01

Objective The effect of end-to-side neurotization of partially regenerated recipient nerves on improving motor power in late obstetric brachial plexus lesions, so-called nerve augmentation, was investigated. Methods Eight cases aged 3 – 7 years were operated upon and followed up for 4 years (C5,6 rupture C7,8T1 avulsion: 5; C5,6,7,8 rupture T1 avulsion:1; C5,6,8T1 rupture C7 avulsion:1; C5,6,7 ruptureC8 T1 compression: one 3 year presentation after former neurotization at 3 months). Grade 1–3 muscles were neurotized. Grade0 muscles were neurotized, if the electromyogram showed scattered motor unit action potentials on voluntary contraction without interference pattern. Donor nerves included: the phrenic, accessory, descending and ascending loops of the ansa cervicalis, 3rd and 4th intercostals and contralateral C7. Results Superior proximal to distal regeneration was observed firstly. Differential regeneration of muscles supplied by the same nerve was observed secondly (superior supraspinatus to infraspinatus regeneration). Differential regeneration of antagonistic muscles was observed thirdly (superior biceps to triceps and pronator teres to supinator recovery). Differential regeneration of fibres within the same muscle was observed fourthly (superior anterior and middle to posterior deltoid regeneration). Differential regeneration of muscles having different preoperative motor powers was noted fifthly; improvement to Grade 3 or more occurred more in Grade2 than in Grade0 or Grade1 muscles. Improvements of cocontractions and of shoulder, forearm and wrist deformities were noted sixthly. The shoulder, elbow and hand scores improved in 4 cases. Limitations The sample size is small. Controls are necessary to rule out any natural improvement of the lesion. There is intra- and interobserver variability in testing muscle power and cocontractions. Conclusion Nerve augmentation improves cocontractions and muscle power in the biceps, pectoral muscles, supraspinatus, anterior and lateral deltoids, triceps and in Grade2 or more forearm muscles. As it is less expected to improve infraspinatus power, it should be associated with a humeral derotation osteotomy and tendon transfer. Function to non improving Grade 0 or 1 forearm muscles should be restored by muscle transplantation. Level of evidence Level IV, prospective case series. PMID:17147803

Distal polyneuropathy in an adult Birman cat with toxoplasmosis.

PubMed

Mari, Lorenzo; Shelton, G Diane; De Risio, Luisa

2016-01-01

A 6-year-old female spayed Birman cat presented with a history of weight loss, stiff and short-strided gait in the pelvic limbs and reluctance to jump, progressing to non-ambulatory tetraparesis over 6 weeks. Poor body condition, dehydration and generalised muscle wastage were evident on general examination. Neurological examination revealed mildly depressed mental status, non-ambulatory flaccid tetraparesis and severely decreased proprioception and spinal reflexes in all four limbs. The neuroanatomical localisation was to the peripheral nervous system. Haematology, feline immunodeficiency virus/feline leukaemia virus serology, serum biochemistry, including creatine kinase and thyroxine, thoracic radiographs and abdominal ultrasound did not reveal significant abnormalities. Electromyography revealed fibrillation potentials and positive sharp waves in axial and appendicular muscles. Decreased motor conduction velocities and compound muscle action potential amplitudes were detected in ulnar and sciatic-tibial nerves. Residual latency was increased in the sciatic-tibial nerve. Histologically, several intramuscular nerve branches were depleted of myelinated fibres and a few showed mononuclear infiltrations. Toxoplasma gondii serology titres were compatible with active toxoplasmosis. Four days after treatment initiation with oral clindamycin the cat recovered the ability to walk. T gondii serology titres and neurological examination were normal after 11 and 16 weeks, respectively. Clindamycin was discontinued after 16 weeks. One year after presentation the cat showed mild relapse of clinical signs and seroconversion, which again resolved following treatment with clindamycin. To our knowledge, this is the first report of distal polyneuropathy associated with toxoplasmosis in a cat. This case suggests the inclusion of toxoplasmosis as a possible differential diagnosis for acquired polyneuropathies in cats.

Double nerve intraneural interface implant on a human amputee for robotic hand control.

PubMed

Rossini, Paolo M; Micera, Silvestro; Benvenuto, Antonella; Carpaneto, Jacopo; Cavallo, Giuseppe; Citi, Luca; Cipriani, Christian; Denaro, Luca; Denaro, Vincenzo; Di Pino, Giovanni; Ferreri, Florinda; Guglielmelli, Eugenio; Hoffmann, Klaus-Peter; Raspopovic, Stanisa; Rigosa, Jacopo; Rossini, Luca; Tombini, Mario; Dario, Paolo

2010-05-01

The principle underlying this project is that, despite nervous reorganization following upper limb amputation, original pathways and CNS relays partially maintain their function and can be exploited for interfacing prostheses. Aim of this study is to evaluate a novel peripheral intraneural multielectrode for multi-movement prosthesis control and for sensory feed-back, while assessing cortical reorganization following the re-acquired stream of data. Four intrafascicular longitudinal flexible multielectrodes (tf-LIFE4) were implanted in the median and ulnar nerves of an amputee; they reliably recorded output signals for 4 weeks. Artificial intelligence classifiers were used off-line to analyse LIFE signals recorded during three distinct hand movements under voluntary order. Real-time control of motor output was achieved for the three actions. When applied off-line artificial intelligence reached >85% real-time correct classification of trials. Moreover, different types of current stimulation were determined to allow reproducible and localized hand/fingers sensations. Cortical organization was observed via TMS in parallel with partial resolution of symptoms due to the phantom-limb syndrome (PLS). tf-LIFE4s recorded output signals in human nerves for 4 weeks, though the efficacy of sensory stimulation decayed after 10 days. Recording from a number of fibres permitted a high percentage of distinct actions to be classified correctly. Reversal of plastic changes and alleviation of PLS represent corollary findings of potential therapeutic benefit. This study represents a breakthrough in robotic hand use in amputees. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity.

PubMed

García-Mesa, Y; García-Piqueras, J; García, B; Feito, J; Cabo, R; Cobo, J; Vega, J A; García-Suárez, O

2017-12-01

The transformation of mechanical energy into electrical signals is the first step in mechanotransduction in the peripheral sensory nervous system and relies on the presence of mechanically gated ion channels within specialized sensory organs called mechanoreceptors. Piezo2 is a vertebrate stretch-gated ion channel necessary for mechanosensitive channels in mammalian cells. Functionally, it is related to light touch, which has been detected in murine cutaneous Merkel cell-neurite complexes, Meissner-like corpuscles and lanceolate nerve endings. To the best of our knowledge, the occurrence of Piezo2 in human cutaneous mechanoreceptors has never been investigated. Here, we used simple and double immunohistochemistry to investigate the occurrence of Piezo2 in human digital glabrous skin. Piezo2 immunoreactivity was detected in approximately 80% of morphologically and immunohistochemically characterized (cytokeratin 20 + , chromogranin A + and synaptophisin + ) Merkel cells. Most of them were in close contact with Piezo2 - nerve fibre profiles. Moreover, the axon, but not the lamellar cells, of Meissner's corpuscles was also Piezo2 + , but other mechanoreceptors, i.e. Pacinian or Ruffini's corpuscles, were devoid of immunoreactivity. Piezo2 was also observed in non-nervous tissue, especially the basal keratinocytes, endothelial cells and sweat glands. The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner's corpuscles) low-threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch. These data offer additional insight into the molecular basis of mechanosensing in humans. © 2017 Anatomical Society.

Exploration of peripapillary vessel density in highly myopic eyes with peripapillary intrachoroidal cavitation and its relationship with ocular parameters using optical coherence tomography angiography.

PubMed

Chen, Qiuying; He, Jiangnan; Hua, Yihong; Fan, Ying

2017-12-01

Identifying changes of peripapillary vessel density in highly myopic eyes with peripapillary intrachoroidal cavitation by optical coherence tomography angiography. To investigate peripapillary vessel density and its relationship with other ocular parameters in highly myopic eyes with peripapillary intrachoroidal cavitation. Hospital-based, cross-sectional study. Thirty-five highly myopic eyes with peripapillary intrachoroidal cavitation, 46 highly myopic eyes without peripapillary intrachoroidal cavitation and 36 normal eyes were included in this study. All participants underwent optical coherence tomography angiography to image the retinal vasculature in the peripapillary areas, including the radial peripapillary capillaries and optic nerve head layer. Correlations between vessel density and ocular metrics were analysed. Peripapillary vessel density. In highly myopic eyes, vessel density was significantly lower in eyes with peripapillary intrachoroidal cavitation than in those without in peripapillary (P = 0.014, P = 0.037), inferotemporal (P < 0.001, P < 0.001) and superotemporal (P = 0.014, P = 0.009) areas. In the radial peripapillary capillaries layer, vessel density was negatively correlated with peripapillary atrophy area (P = 0.012) and myopic maculopathy (P = 0.002), and in the optic nerve head layer, it was negatively associated with a diagnosis of peripapillary intrachoroidal cavitation (P = 0.012) and myopic maculopathy (P < 0.001). In addition, it was positively correlated with retinal nerve fibre layer thickness in both layers (P < 0.001). Highly myopic eyes with peripapillary intrachoroidal cavitation had lower peripapillary vessel densities, especially in the temporal area, than those without. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Selective effects of an octopus toxin on action potentials

PubMed Central

Dulhunty, Angela; Gage, Peter W.

1971-01-01

1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

Anatomical mapping of choline acetyltransferase (ChAT)-like and glutamate decarboxylase (GAD)-like immunoreactivity in outer hair cell efferents in adult rats.

PubMed

Dannhof, B J; Roth, B; Bruns, V

1991-10-01

The distribution of choline acetyltransferase (ChAT)-like and glutamate decarboxylase (GAD)-like immunoreactivity in the cochleae of 15 adult Wistar white rats was investigated using the peroxidase-antiperoxidase (PAP) technique. A monoclonal antibody to ChAT and a polyclonal antiserum to GAD were used. Immunoreaction was investigated quantitatively, in the electron microscope, on tangential sections of the tunnel of Corti and the rows of outer hair cells. ChAT-like and GAD-like immunoreactivity was found in all efferent nerve fibres in the tunnel of Corti and in all efferent synapses on the outer hair cells. A coexistence of ChAT and GAD in the efferent system to the outer hair cells of the rat is therefore assumed.

Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge.

PubMed

Michel, K; Michaelis, M; Mazzuoli, G; Mueller, K; Vanden Berghe, P; Schemann, M

2011-12-15

Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by -conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores.

Revealing fine microstructural morphology in the living human retina using Optical Coherence Tomography with pancorrection

NASA Astrophysics Data System (ADS)

Torti, C.; Považay, B.; Hofer, B.; Unterhuber, A.; Hermann, B.; Drexler, W.

2008-09-01

Ultra-high speed optical coherence tomography employing an ultra-broadband light source has been combined with adaptive optics utilizing a single high stroke deformable mirror and chromatic aberration compensation. The reduction of motion artefacts, geometric and chromatic aberrations (pancorrection) permits to achieve an isotropic resolution of 2-3 μm in the human eye. The performance of this non-invasive imaging modality enables to resolve cellular structures including cone photoreceptors, nerve fibre bundles and collagenous plates of the lamina cribrosa, and retinal pigment epithelial (RPE) cells in the human retina in vivo with superior detail. Alterations of cellular morphology due to cone degeneration in a colour-blind subject are investigated in ultra-high resolution with selective depth sectioning for the first time.

The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model

PubMed Central

Jokic, Natasa; Gonzalez de Aguilar, Jose-Luis; Dimou, Leda; Lin, Shuo; Fergani, Anissa; Ruegg, Markus A; Schwab, Martin E; Dupuis, Luc; Loeffler, Jean-Philippe

2006-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss and muscle wasting. In muscles of ALS patients, Nogo-A—a protein known to inhibit axon regeneration—is ectopically expressed at levels that correlate with the severity of the clinical symptoms. We now show that the genetic ablation of Nogo-A extends survival and reduces muscle denervation in a mouse model of ALS. In turn, overexpression of Nogo-A in wild-type muscle fibres leads to shrinkage of the postsynapse and retraction of the presynaptic motor ending. This suggests that the expression of Nogo-A occurring early in ALS skeletal muscle could cause repulsion and destabilization of the motor nerve terminals, and subsequent dying back of the axons and motor neurons. PMID:17039253

Angiotensin II type 2 receptor (AT2R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons

PubMed Central

Anand, U; Facer, P; Yiangou, Y; Sinisi, M; Fox, M; McCarthy, T; Bountra, C; Korchev, YE; Anand, P

2013-01-01

Background The angiotensin II (AngII) receptor subtype 2 (AT2R) is expressed in sensory neurons and may play a role in nociception and neuronal regeneration. Methods We used immunostaining with characterized antibodies to study the localization of AT2R in cultured human and rat dorsal root ganglion (DRG) neurons and a range of human tissues. The effects of AngII and AT2R antagonist EMA401 on capsaicin responses in cultured human and rat (DRG) neurons were measured with calcium imaging, on neurite length and density with Gap43 immunostaining, and on cyclic adenosine monophosphate (cAMP) expression using immunofluorescence. Results AT2R expression was localized in small-/medium-sized cultured neurons of human and rat DRG. Treatment with the AT2R antagonist EMA401 resulted in dose-related functional inhibition of capsaicin responses (IC50 = 10 nmol/L), which was reversed by 8-bromo-cAMP, and reduced neurite length and density; AngII treatment significantly enhanced capsaicin responses, cAMP levels and neurite outgrowth. The AT1R antagonist losartan had no effect on capsaicin responses. AT2R was localized in sensory neurons of human DRG, and nerve fibres in peripheral nerves, skin, urinary bladder and bowel. A majority sub-population (60%) of small-/medium-diameter neuronal cells were immunopositive in both control post-mortem and avulsion-injured human DRG; some very small neurons appeared to be intensely immunoreactive, with TRPV1 co-localization. While AT2R levels were reduced in human limb peripheral nerve segments proximal to injury, they were preserved in painful neuromas. Conclusions AT2R antagonists could be particularly useful in the treatment of chronic pain and hypersensitivity associated with abnormal nerve sprouting. PMID:23255326

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

PubMed

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

2017-05-01

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

Implication of NMDA type glutamate receptors in neural regeneration and neoformation of synapses after excitotoxic injury in the guinea pig cochlea.

PubMed

d'Aldin, C G; Ruel, J; Assié, R; Pujol, R; Puel, J L

1997-07-01

In the adult mammalian cochlea, the ability of nerve fibres to regenerate has been observed following disruption of the organ of Corti by various means, or transsection of the cochlear nerve in the internal auditory meatus. Based upon the implication of glutamate as a neurotransmitter at synapses between sensory hair cells and terminal dendrites of the auditory nerve in the mammalian cochlea, we have developed, in a previous study, an in vivo model of neural regeneration and formation of synapses after the destruction of the afferent nerve endings by local application of the glutamate agonist alpha-amino-3-hydroxy-5-methyl-isoxazol-propionic acid (AMPA). In situ hybridization experiments performed during the re-innervation process revealed an overexpression of mRNA coding for NR1 subunit of N-methyl-D-aspartate (NMDA) receptors in the spiral ganglion neurons, suggesting that these receptors are implicated in neural regenerative processes. The present study has been designed to study the functional implication of NMDA receptors in the regrowth and synaptic repair of auditory dendrites in the guinea pig cochlea, by blocking the NMDA receptors during the period of normal functional recovery. In a first set of experiments, we recorded compound action potential after acute perilymphatic perfusion of cumulative doses (0.03-10mM) of DL 2-amino-5-phosphonovalerate (D-AP5), a NMDA antagonist, to determine the efficiency of the drug. In a second set of experiments, the auditory dendrites were destroyed by local application of the glutamate agonist AMPA. The blockage of NMDA by the antagonist D-AP5 applied with an osmotic micropump delayed the functional recovery and the regrowth of auditory dendrites. The findings of our study support the hypothesis that, in addition to acting as a fast transmitter, glutamate has a neurotrophic role via the activation of NMDA receptors.

Time course of the soleus M response and H reflex after lidocaine tibial nerve block in the rat.

PubMed

Buffenoir, Kévin; Decq, Philippe; Pérot, Chantal

2013-01-01

In spastic subjects, lidocaine is often used to induce a block predictive of the result provided by subsequent surgery. Lidocaine has been demonstrated to inhibit the Hoffmann (H) reflex to a greater extent than the direct motor (M) response induced by electrical stimulation, but the timecourse of these responses has not been investigated. An animal (rat) model of the effects of lidocaine on M and H responses was therefore developed to assess this time course. M and H responses were recorded in 18 adult rats before and after application of lidocaine to the sciatic nerve. Two to five minutes after lidocaine injection, M responses were markedly reduced (mean reduction of 44%) and H reflexes were completely abolished. Changes were observed more rapidly for the H reflex. The effects of lidocaine then persisted for 100 minutes. The effect of lidocaine was therefore more prolonged on the H reflex than on the M response. This study confirms that lidocaine blocks not only alpha motoneurons but also Ia afferent fibres responsible for the H reflex. The authors describe, for the first time, the detailed time course of the effect of lidocaine on direct or reflex activation of motoneurons in the rat.

Electrical responses of isolated protoplasm from Nitella.

PubMed

Koppenhöfer, E

1975-07-21

Isolated protoplasmic droplets of the alga Nitella were investigated with microelectrodes in artificial vacuolar sap. The following observations were made: 1. Two types of preparations could be distinguished differing in size and in time of adaptation to artificial pond water but only slightly in their electrical behaviour. 2. The droplets proved to be electrically excitable in the sense that short current pulses elicited electrical responses which outlasted the stimuli. 3. The responses resembled nerve action potentials in shape and duration but they were graded and could be elicited as well in positive as in negative direction. Moreover, spontaneous changes of the normal resting potential (a few millivolts inside negative) did not influence their amplitudes. 4. In most cases the amplitudes of the responses grew with time and saturated after about 90 min. Before saturation the relation between stimulus strength and amplitude of responses was almost linear but became slightly S-shaped after saturation. The saturation value of the responses caused by 100 mus pulses of 1 muA/mm2 was taken as a standard response. In 32 experiments the standard response varied considerable between 2 and 90 mV and was 13 mV on the average. The observations suggest that quite different mechanisms are responsible for the transients of the Nitella droplets and the all-or-none responses of nerve fibres.