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Sample records for nerve cell activity

  1. Upregulation of Nuclear Factor of Activated T-Cells by Nerve Injury Contributes to Development of Neuropathic Pain

    OpenAIRE

    Cai, You-qing; Chen, Shao-rui; Pan, Hui-lin

    2013-01-01

    Nerve injury induces long-term changes in gene expression in the nociceptive circuitry and can lead to chronic neuropathic pain. However, the transcriptional mechanism involved in neuropathic pain is poorly understood. Nuclear factor of activated T-cells (NFATc) is a transcriptional factor regulated by the Ca2+-dependent protein phosphatase calcineurin. In this study, we determined nerve injury–induced changes in the expression of NFATc1–c4 in the dorsal root ganglia (DRG) and spinal cord...

  2. Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats

    Directory of Open Access Journals (Sweden)

    Kanje Martin

    2011-01-01

    Full Text Available Abstract Background Extracellular-signal regulated kinase (ERK1/2 is activated by nerve damage and its activation precedes survival and proliferation of Schwann cells. In contrast, activation of caspase 3, a cysteine protease, is considered as a marker for apoptosis in Schwann cells. In the present study, axonal outgrowth, activation of ERK1/2 by phosphorylation (p-ERK 1/2 and immunoreactivity of cleaved caspase 3 were examined after immediate, delayed, or no repair of transected rat sciatic nerves. Results Axonal outgrowth, detected by neurofilament staining, was longer after immediate repair than after either the delayed or no repair conditions. Immediate repair also showed a higher expression of p-ERK 1/2 and a lower number of cleaved caspase 3 stained Schwann cells than after delayed nerve repair. If the transected nerve was not repaired a lower level of p-ERK 1/2 was found than in either the immediate or delayed repair conditions. Axonal outgrowth correlated to p-ERK 1/2, but not clearly with cleaved caspase 3. Contact with regenerating axons affected Schwann cells with respect to p-ERK 1/2 and cleaved caspase 3 after immediate nerve repair only. Conclusion The decreased regenerative capacity that has historically been observed after delayed nerve repair may be related to impaired activation of Schwann cells and increased Schwann cell death. Outgrowing axons influence ERK 1/2 activation and apoptosis of Schwann cells.

  3. Osteopontin Is Induced by TGF-?2 and Regulates Metabolic Cell Activity in Cultured Human Optic Nerve Head Astrocytes

    OpenAIRE

    Neumann, Carolin; Garreis, Fabian; Paulsen, Friedrich; Hammer, Christian M.; Birke, Marco T.; Scholz, Michael

    2014-01-01

    The aqueous humor (AH) component transforming growth factor (TGF)-?2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary ocular cells. Here we present osteopontin (OPN) as a new TGF-?2 responsive factor in cultured human optic nerve head (ONH) astrocytes. Activation was initially demonstrated by Oligo GEArray microar...

  4. Docosahexaenoic acid decreases phospholipase A2 activity in the neurites/nerve growth cones of PC12 cells.

    Science.gov (United States)

    Martin, R E

    1998-12-15

    Docosahexaenoic acid (DHA) accumulates in nerve growth cones (NGC) during perinatal development and it is neuroprotective in ischemia. Because the phospholipases A2 (PLA2) are present in NGC and these enzymes function in both ischemia and long-term potentiation, the relationship between DHA and PLA2 was investigated in the NGC of nerve growth factor-differentiated PC12 cells. When PC12 cells were incubated with [3H]DHA, it primarily esterified in ethanolamine glycerolipids and concentrated initially in cell bodies with similar levels present in the neurite/nerve growth cone (N/NGC) fraction after 4 days. PLA2 activity in the N/NGC fraction was investigated using [14C]arachidonic acid-labeled phosphatidylinositol ([14C-AA]PI) as substrate. Heat denaturation and pharmacological inhibition showed that much of the PLA2 activity was calcium-independent and secretory rather than cytosolic. Supplementing the media with as little as 33 nM DHA significantly reduced PLA2 activity in the N/NGC fraction. PMID:9856864

  5. Expression of Activating Transcription Factor 3 (ATF 3) and caspase 3 in Schwann cells and axonal outgrowth after sciatic nerve repair in diabetic BB rats.

    OpenAIRE

    Stenberg, Lena; Kanje, Martin; Dolezal, Katarina; Dahlin, Lars

    2012-01-01

    The aim of this study was to evaluate nerve regeneration in relation to the transcription factor, Activating Transcription Factor 3 (ATF 3), and an apoptotic marker, caspase 3, in the Schwann cells of diabetic BB rats (i.e. display type 1 diabetes phenotype). Sciatic nerves in healthy Wistar rats and in diabetic BB rats were transected and immediately repaired. Axonal outgrowth (neurofilament staining) and expression of ATF 3 and caspase 3 were quantified by immunohistochemistry after six day...

  6. Nerve compression activates selective nociceptive pathways and upregulates peripheral sodium channel expression in Schwann cells.

    Science.gov (United States)

    Frieboes, Laura Rummler; Palispis, Winnie Anne; Gupta, Ranjan

    2010-06-01

    Chronic nerve compression (CNC) injuries, such as carpal tunnel syndrome, are common musculoskeletal conditions that affect patients with debilitating loss of sensory function and pain. Although early detection and treatment are important, our understanding of pain-related molecular mechanisms remains largely unclear. Here we investigate these mechanisms using an animal model for CNC injury. To confirm that CNC injury induces pain, we assessed expression of c-fos, a gene that is rapidly expressed in spinal sensory afferents in response to painful peripheral stimuli, and TNF-alpha and IL-6, two proinflammatory cytokines that are crucial to development of inflammatory-mediated pain. Results show c-fos upregulation 1-2 weeks postinjury in the absence of TNF-alpha or IL-6 expression, indicating increased neural sensitivity without an inflammatory response. This is consistent with previous studies that showed no morphologic evidence of inflammation in the CNC model. Surprisingly, we also found de novo expression of Na(V)1.8, a sodium channel linked to the development of neuropathic pain, in endoneurial Schwann cells following injury. Until now, Na(V)1.8 expression was thought to be restricted to sensory neurons. CNC injury appears to be a unique model of noninflammatory neuropathic pain. Further investigation of the underlying molecular basis could yield promising targets for early diagnosis and treatment. PMID:20014316

  7. Perceptual consequences of disrupted auditory nerve activity.

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    Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

    2005-06-01

    Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique contribution of neural synchrony to sensory perception but also provide guidance for translational research in terms of better diagnosis and management of human communication disorders. PMID:15615831

  8. Activation of MAPK ERK in peripheral nerve after injury

    Directory of Open Access Journals (Sweden)

    Tanomsridejchai N

    2006-06-01

    Full Text Available Abstract Background Activation of extracellular signal-regulated protein kinase (ERK, a member of mitogen-activated protein kinase (MAPK family, has been proposed to mediate neurite outgrowth-promoting effects of several neurotrophic factors in vitro. However, the precise activity of ERK during axonal regeneration in vivo remains unclear. Peripheral axotomy has been shown to activate ERK in the cell bodies of primary afferent neurons and associated satellite cells. Nevertheless, whether ERK is also activated in the axons and surrounded Schwann cells which also play a key role in the regeneration process has not been clarified. Results Phosphorylation of ERK in the sciatic nerve in several time-points after crush injury has been examined. Higher phosphorylation of ERK was observed in the proximal and distal nerve stumps compared to the contralateral intact nerve from one day to one month after crush. The activation of ERK was mainly localized in the axons of the proximal segments. In the distal segments, however, active ERK was predominantly found in Schwann cells forming Bungner's bands. Conclusion The findings indicate that ERK is activated in both the proximal and distal nerve stumps following nerve injury. The role of activated ERK in Wallerian degeneration and subsequent regeneration in vivo remains to be elucidated.

  9. Putative intermediates in the nerve cell differentiation pathway in hydra have properties of multipotent stem cells

    International Nuclear Information System (INIS)

    We have investigated the properties of nerve cell precursors in hydra by analyzing the differentiation and proliferation capacity of interstitial cells in the peduncle of Hydra oligactis, which is a region of active nerve cell differentiation. Our results indicate that about 50% of the interstitial cells in the peduncle can grow rapidly and also give rise to nematocyte precursors when transplanted into a gastric environment. If these cells were committed nerve cell precursors, one would not expect them to differentiate into nematocytes nor to proliferate apparently without limit. Therefore we conclude that cycling interstitial cells in peduncles are not intermediates in the nerve cell differentiation pathway but are stem cells. The remaining interstitial cells in the peduncle are in G1 and have the properties of committed nerve cell precursors. Thus, the interstitial cell population in the peduncle contains both stem cells and noncycling nerve precursors. The presence of stem cells in this region makes it likely that these cells are the immediate targets of signals which give rise to nerve cells

  10. Stem cell salvage of injured peripheral nerve.

    Science.gov (United States)

    Grimoldi, Nadia; Colleoni, Federica; Tiberio, Francesca; Vetrano, Ignazio G; Cappellari, Alberto; Costa, Antonella; Belicchi, Marzia; Razini, Paola; Giordano, Rosaria; Spagnoli, Diego; Pluderi, Mauro; Gatti, Stefano; Morbin, Michela; Gaini, Sergio M; Rebulla, Paolo; Bresolin, Nereo; Torrente, Yvan

    2015-01-01

    We previously developed a collagen tube filled with autologous skin-derived stem cells (SDSCs) for bridging long rat sciatic nerve gaps. Here we present a case report describing a compassionate use of this graft for repairing the polyinjured motor and sensory nerves of the upper arms of a patient. Preclinical assessment was performed with collagen/SDSC implantation in rats after sectioning the sciatic nerve. For the patient, during the 3-year follow-up period, functional recovery of injured median and ulnar nerves was assessed by pinch gauge test and static two-point discrimination and touch test with monofilaments, along with electrophysiological and MRI examinations. Preclinical experiments in rats revealed rescue of sciatic nerve and no side effects of patient-derived SDSC transplantation (30 and 180 days of treatment). In the patient treatment, motor and sensory functions of the median nerve demonstrated ongoing recovery postimplantation during the follow-up period. The results indicate that the collagen/SDSC artificial nerve graft could be used for surgical repair of larger defects in major lesions of peripheral nerves, increasing patient quality of life by saving the upper arms from amputation. PMID:24268028

  11. Synaptic inhibition in an isolated nerve cell.

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    KUFFLER, S W; EYZAGUIRRE, C

    1955-09-20

    Following the preceding studies on the mechanisms of excitation in stretch receptor cells of crayfish, this investigation analyzes inhibitory activity in the synapses formed by two neurons. The cell body of the receptor neuron is located in the periphery and sends dendrites into a fine muscle strand. The dendrites receive innervation through an accessory nerve fiber which has now been established to be inhibitory. There exists a direct peripheral inhibitory control mechanism which can modulate the activity of the stretch receptor. The receptor cell which can be studied in isolation was stimulated by stretch deformation of its dendrites or by antidromic excitation and the effect of inhibitory impulses on its activity was analyzed. Recording was done mainly with intracellular leads inserted into the cell body. 1. Stimulation of the relatively slowly conducting inhibitory nerve fiber either decreases the afferent discharge rate or stops impulses altogether in stretched receptor cells. The inhibitory action is confined to the dendrites and acts on the generator mechanism which is set up by stretch deformation. By restricting depolarization of the dendrites above a certain level, inhibition prevents the generator potential from attaining the "firing level" of the cell. 2. The same inhibitory impulse may set up a postsynaptic polarization or a depolarization, depending on the resting potential level of the cell. The membrane potential at which the inhibitory synaptic potential reverses its polarity, the equilibrium level, may vary in different preparations. The inhibitory potentials increase as the resting potential is displaced in any direction from the inhibitory equilibrium. 3. The inhibitory potentials usually rise to a peak in about 2 msec. and decay in about 30 msec. After repetitive inhibitory stimulation a delayed secondary polarization phase has frequently been seen, prolonging the inhibitory action. Repetitive inhibitory excitation may also be followed by a period of facilitation. Some examples of "direct" excitation by the depolarizing action of inhibitory impulses are described. 4. The interaction between antidromic and inhibitory impulses was studied. The results support previous conclusions (a) that during stretch the dendrites provide a persisting "drive" for the more central portions of the receptor cell, and (b) that antidromic all-or-none impulses do not penetrate into the distal portions of stretch-depolarized dendrites. The "after-potentials" of antidromic impulses are modified by inhibition. 5. Evidence is presented that inhibitory synaptic activity increases the conductance of the dendrites. This effect may occur in the absence of inhibitory potential changes. PMID:13252239

  12. Lipid extraction from isolated single nerve cells

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    Krasnov, I. V.

    1977-01-01

    A method of extracting lipids from single neurons isolated from lyophilized tissue is described. The method permits the simultaneous extraction of lipids from 30-40 nerve cells and for each cell provides equal conditions of solvent removal at the conclusion of extraction.

  13. Induced-pluripotent stem cells seeded acellular peripheral nerve graft as “autologous nerve graft”

    OpenAIRE

    Ti-Fei Yuan; Guo-Dong Gao; Jiang Li

    2010-01-01

    The hypothesis is that induced pluripotent stem cells (iPSC) derived Schwann cells and/or macrophages can be transplanted into acellular nerve graft in repairing injured nervous system. The efficiency of iPSC seeded acellular nerve graft may mimic the autologous peripheral nerve graft.

  14. Nardosinone enhances nerve growth factor-induced neurite outgrowth in a mitogen-activated protein kinase- and protein kinase C-dependent manner in PC12D cells.

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    Li, Ping; Yamakuni, Tohru; Matsunaga, Kimihiro; Kondo, Shunzo; Ohizumi, Yasushi

    2003-09-01

    The mechanism to enhance nerve growth factor (NGF, 2 ng/ml)-induced neurite outgrowth from PC12D cells by nardosinone isolated from Nardostachys chinensis was examined. It was shown that the potentiation of the NGF-induced neurite outgrowth by nardosinone was mitogen-activated protein (MAP) kinase-dependent, but was not accompanied by stimulation of NGF-induced increase in MAP kinase phosphorylation. Furthermore, this augmentation of NGF-induced neurite outgrowth was abolished by GF109203X, a protein kinase C (PKC) inhibitor. These results suggest that the enhancement of NGF-induced neurite outgrowth from PC12D cells by nardosinone involves activation of a down-stream step of the MAP kinase-dependent cascade of NGF coupled with PKC. PMID:14501162

  15. A plasminogen activator is induced during goldfish optic nerve regeneration.

    OpenAIRE

    Salle?s, F. J.; Schechter, N.; Strickland, S.

    1990-01-01

    The use of purified piscine plasminogen in a chromogenic solution assay enabled us to detect plasminogen activator (PA) activity in crude homogenates of goldfish optic nerve following nerve injury. In contrast, no activity was detected in the homogenates of uninjured nerve. Under conditions allowing regeneration of the optic axons (optic nerve crush), PA activity peaked 8 days after crush, and decreased to undetectable levels by 60 days. Under conditions allowing only degeneration of the axon...

  16. The differentiation of the newborn nerve cells in oculomotor nuclear after oculomotor nerve injury.

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    Yang, Min; Zhu, Ningxi; Meng, Youqiang; Wang, Xuhui; Zhong, Jun; Wan, Liang; Zhang, Wenchuan; Visocchi, Massimiliano; Zhu, Shugan; Li, Shiting

    2011-04-01

    Oculomotor nerve injury is a common complication of cranial trauma and craniotomy. For a long time, it has been generally considered that the oculomotor nerve is unable to regenerate and recover functionally after injury. With the development of neuroradiology, microsurgery and neurohistology, it has been reported that the injured oculomotor nerve could be repaired by operation. However, the mechanisms of neural regeneration of the injured oculomotor nerve remain obscure. Therefore, by investigating the differentiation of the newborn nerve cells in oculomotor nuclear after oculomotor nerve injury, the mechanisms of the neural regeneration of the injured oculomotor nerve was studied in the present paper. After animal model establishment, we found that the function of the injured oculomotor nerve could recover at some degree without treatment, at fourth week after the nerve injury. This result confirms that the injured oculomotor nerve per se has the potential to regenerate and repair. At the present study, by BredU stain, BrdU labeling cells were observed in oculomotor nuclear at the fourth week post-operatively. It indicated that the oculomotor nuclear per se has the ability of generating the cells, which will regenerate and differentiate after the nerve injury, without stimulation by exogenous agents. Immunofluorescence double staining was used in this study to show the differentiation of the newborn cells in oculomotor nuclear after oculomotor nerve injury. It is found that they could differentiate into neural progenitor cells, neuronal cells and neuroglial cells. It is suggested that the different differentiation of cells may play a role in the nerve regeneration procedure. PMID:21301911

  17. Denervated sheath cells secrete a new protein after nerve injury.

    OpenAIRE

    Skene, J. H.; Shooter, E. M.

    1983-01-01

    When rat sciatic nerves are crushed, Schwann cells or other supporting cells distal to the injury site begin to synthesize and secrete an acidic 37-kilodalton (kDa) protein. This crush-induced protein accumulates within the nerve sheath and accounts for 2-5% of the total extracellular protein in the distal nerve stump. Synthesis of the 37-kDa protein increased for 2 weeks after nerve crush and declines slowly, beginning 4-6 weeks after the injury. The synthesis of the protein may be regulated...

  18. Selective activation of the human tibial and common peroneal nerves with a flat interface nerve electrode

    Science.gov (United States)

    Schiefer, M. A.; Freeberg, M.; Pinault, G. J. C.; Anderson, J.; Hoyen, H.; Tyler, D. J.; Triolo, R. J.

    2013-10-01

    Objective. Electrical stimulation has been shown effective in restoring basic lower extremity motor function in individuals with paralysis. We tested the hypothesis that a flat interface nerve electrode (FINE) placed around the human tibial or common peroneal nerve above the knee can selectively activate each of the most important muscles these nerves innervate for use in a neuroprosthesis to control ankle motion. Approach. During intraoperative trials involving three subjects, an eight-contact FINE was placed around the tibial and/or common peroneal nerve, proximal to the popliteal fossa. The FINE's ability to selectively recruit muscles innervated by these nerves was assessed. Data were used to estimate the potential to restore active plantarflexion or dorsiflexion while balancing inversion and eversion using a biomechanical simulation. Main results. With minimal spillover to non-targets, at least three of the four targets in the tibial nerve, including two of the three muscles constituting the triceps surae, were independently and selectively recruited in all subjects. As acceptable levels of spillover increased, recruitment of the target muscles increased. Selective activation of muscles innervated by the peroneal nerve was more challenging. Significance. Estimated joint moments suggest that plantarflexion sufficient for propulsion during stance phase of gait and dorsiflexion sufficient to prevent foot drop during swing can be achieved, accompanied by a small but tolerable inversion or eversion moment.

  19. Peripheral nerve injury activates convergent nociceptive input to dorsal horn neurons from neighboring intact nerve.

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    Terayama, Ryuji; Yamamoto, Yuya; Kishimoto, Noriko; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that peripheral nerve injury induced excessive nociceptive response of spinal cord dorsal horn neurons and such change has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the spinal dorsal horn for convergence of nociceptive input to second-order neurons deafferented by peripheral nerve injury. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input to spinal dorsal horn neurons after the saphenous nerve injury. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and by electrical stimulation of the injured or uninjured saphenous nerve, respectively. Within the central terminal field of the saphenous nerve, the number of c-Fos protein-like immunoreactive (c-Fos-IR) cell profiles was significantly decreased at 3 days and returned to the control level by 14 days after the injury. p-ERK immunoreactive (p-ERK-IR) cell profiles were distributed in the central terminal field of the saphenous nerve, and the topographic distribution pattern and number of such p-ERK-IR cell profiles remained unchanged after the nerve injury. The time course of changes in the number of double-labeled cell profiles was similar to that of c-Fos-IR cell profiles after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves contributes to increased responsiveness of spinal dorsal horn nociceptive neurons. PMID:25600819

  20. Proteasome Inhibitors Prevent Oxidative Stress-Induced Nerve Cell Death by a Novel Mechanism

    OpenAIRE

    Maher, Pamela

    2008-01-01

    The role of the proteasome in neurodegenerative diseases is controversial. On the one hand, there is evidence that a dysfunction of proteasome activity can lead to neurodegeneration but there is also data showing that proteasome inhibition can protect nerve cells from a variety of insults. In an attempt to clarify this issue, we studied the effects of four different proteasome inhibitors in a well characterized model of oxidative stress-induced nerve cell death. Consistent with the hypothesis...

  1. Regulation of nerve growth factor biosynthesis by beta-adrenergic receptor activation in astrocytoma cells: a potential role of c-Fos protein.

    OpenAIRE

    Mocchetti, I.; Bernardi, M. A.; Szekely, A. M.; Alho, H.; Brooker, G.; Costa, E.

    1989-01-01

    The chain of events that results in increased production of nerve growth factor (NGF) following beta-adrenergic receptor (BAR) stimulation has been investigated in the C6-2B rat astrocytoma cell line. Exposure of these cells to the BAR agonist isoproterenol elicits the following cascade of events: (i) increase of cAMP content; (ii) increase of c-Fos mRNA content; (iii) accumulation of c-Fos protein immunoreactivity in the nucleus; (iv) increase of NGF mRNA content. The increase in c-Fos mRNA ...

  2. Denervated sheath cells secrete a new protein after nerve injury.

    Science.gov (United States)

    Skene, J H; Shooter, E M

    1983-07-01

    When rat sciatic nerves are crushed, Schwann cells or other supporting cells distal to the injury site begin to synthesize and secrete an acidic 37-kilodalton (kDa) protein. This crush-induced protein accumulates within the nerve sheath and accounts for 2-5% of the total extracellular protein in the distal nerve stump. Synthesis of the 37-kDa protein increased for 2 weeks after nerve crush and declines slowly, beginning 4-6 weeks after the injury. The synthesis of the protein may be regulated by axon-Schwann cell contact. The specific induction of the 37-kDa protein and its accumulation in the extracellular space during nerve regeneration suggest that the protein promotes some aspect of axon growth. Because it is induced slowly after injury, the 37-kDa protein is unlikely to stimulate initial outgrowth of axons; however, it might promote later neuronal responses related to axon growth. The sciatic nerve supporting cells also respond to denervation by reducing the synthesis and release of two proteins of molecular mass 51 and 54 kDa. After crush injury to rat optic nerves, glial cells in the distal optic nerve stump also begin to synthesize and release an acidic 37-kDa protein, although axons of this central nervous system tract do not regenerate. If the 37-kDa protein from peripheral nerves proves to participate in the support of axon regrowth, then the results with rat optic nerve suggest that central nervous system glia initiate at least one part of an appropriate response to nerve injury. PMID:6575401

  3. Early interfaced neural activity from chronic amputated nerves

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    KshitijaGarde

    2009-05-01

    Full Text Available Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .

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

    International Nuclear Information System (INIS)

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

  5. Peripheral nerve extract effects on mesenchymal cells.

    OpenAIRE

    Dietz, F. R.; Mukhopadhyay, B; Becker, G.; Daniels, K; Solursh, M

    1996-01-01

    Several common congenital limb disorders are characterized by normal tissue differentiation but abnormal somatic growth. These include: idiopathic clubfoot, idiopathic leg length discrepancy, hemi-atrophy and hemi-hypertrophy. Both clinical and research studies have suggested that peripheral nerves may be important in regulating somatic growth of limb tissues. To investigate the hypothesis that peripheral nerves convey trophic substances to mesenchymal tissues that are involved in the regulat...

  6. Angiotensin and peripheral sympathetic nerve activity

    Science.gov (United States)

    Benelli, G.; Della Bella, D.; Gandini, A.

    1964-01-01

    On the isolated vas deferens of the guinea-pig angiotensin potentiated strongly the height of contractions due to electrical stimulation of the hypogastric nerve; it did not affect the responses to noradrenaline and acetylcholine, nor did it elicit any contraction when given alone. Angiotensin likewise potentiated the responses of the cat spleen to nerve stimulation, but it also induced by itself strong contractions of the organ and reduction of the venous outflow. In experiments on the arterial blood pressure of anaesthetized and spinal cats, in which sympathetic postganglionic transmission was temporarily blocked by nicotine or tetramethylammonium, pressor responses to angiotensin were strongly reduced. As with some ganglion-stimulating drugs, the pressor responses, enhanced after a second series of nicotine injections, were reduced to the control level by hexamethonium. These findings indicate the involvement of peripheral sympathetic nerves in the action of angiotensin: the hypothesis is advanced that angiotensin acts at the peripheral nerve endings by promoting a greater output of noradrenaline. PMID:14126053

  7. In Vitro Evaluation of Cell-Seeded Chitosan Films for Peripheral Nerve Tissue Engineering

    Science.gov (United States)

    Wrobel, Sandra; Serra, Sofia Cristina; Ribeiro-Samy, Silvina; Sousa, Nuno; Heimann, Claudia; Barwig, Christina; Grothe, Claudia; Haastert-Talini, Kirsten

    2014-01-01

    Natural biomaterials have attracted an increasing interest in the field of tissue-engineered nerve grafts, representing a possible alternative to autologous nerve transplantation. With the prospect of developing a novel entubulation strategy for transected nerves with cell-seeded chitosan films, we examined the biocompatibility of such films in vitro. Different types of rat Schwann cells (SCs)—immortalized, neonatal, and adult—as well as rat bone-marrow-derived mesenchymal stromal cells (BMSCs) were analyzed with regard to their cell metabolic activity, proliferation profiles, and cell morphology after different time points of mono- and cocultures on the chitosan films. Overall the results demonstrate a good cytocompatibility of the chitosan substrate. Both cell types were viable on the biomaterial and showed different metabolic activities and proliferation behavior, indicating cell-type-specific cell–biomaterial interaction. Moreover, the cell types also displayed their typical morphology. In cocultures adult SCs used the BMSCs as a feeder layer and no negative interactions between both cell types were detected. Further, the chitosan films allow neurite outgrowth from dissociated sensory neurons, which is additionally supported on film preseeded with SC-BMSC cocultures. The presented chitosan films therefore demonstrate high potential for their use in tissue-engineered nerve grafts. PMID:24606318

  8. Extraction of nerve cells in images with herpetic infections.

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    Nedzved, A; Ablameyko, S; Oczeretko, E

    2005-01-01

    In this paper, algorithms for extracting and diagnosis of nerve cells with herpetic infections are proposed. Degree of herpetic lesions is divided into four classes. Morphological characteristic of herpetic lesions for cell is accomplished by analyze cells structure. Because virus of herpes change shape of nucleus. Therefore automated analysis of herpetic lesion carry out by morphology segmentation and cells structure identification. The algorithms have been successfully used in practical systems and showed good results. PMID:16358984

  9. In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction injury following mesenchymal stem cell transplantation

    International Nuclear Information System (INIS)

    Objective: To assess the continuous process of nerve regeneration in acute peripheral nerve traction injury treated with mesenchymal stem cells (MSCs) transplantation using MRI. Materials and methods: 1 week after acute nerve traction injury was established in the sciatic nerve of 48 New Zealand white rabbits, 5 × 105 MSCs and vehicle alone were grafted to the acutely distracted sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the injured nerves were performed with a 1.5-T scanner and functional recovery was recorded over a 10-week follow-up period, with histological assessments performed at regular intervals. Results: Compared with vehicle control, nerves grafted with MSCs had better functional recovery and showed improved nerve regeneration, with a sustained increase of T1 and T2 values during the phase of regeneration. Conclusion: MRI could be used to monitor the enhanced nerve regeneration in acute peripheral nerve traction injury treated with MSC transplantation, reflected by a prolonged increase in T1 and T2 values of the injured nerves

  10. 'Green mice' display limitations in enhanced green fluorescent protein expression in retina and optic nerve cells.

    Science.gov (United States)

    Caminos, Elena; Vaquero, Cecilia F; García-Olmo, Dolores C

    2014-12-01

    Characterization of retinal cells, cell transplants and gene therapies may be helped by pre-labeled retinal cells, such as those transfected with vectors for green fluorescent protein expression. The aim of this study was to analyze retinal cells and optic nerve components from transgenic green mice (GM) with the 'enhanced' green fluorescent protein (EGFP) gene under the control of the CAG promoter (a chicken ?-actin promoter and a cytomegalovirus enhancer). The structural analysis and electroretinography recordings showed a normal, healthy retina. Surprisingly, EGFP expression was not ubiquitously located in the retina and optic nerve. Epithelial cells, photoreceptors and bipolar cells presented high green fluorescence levels. In contrast, horizontal cells, specific amacrine cells and ganglion cells exhibited a null EGFP expression level. The synaptic terminals of rod bipolar cells displayed a high green fluorescence level when animals were kept in the dark. Immature retinas exhibited different EGFP expression patterns to those noted in adults. Axons and glial cells in the optic nerve revealed a specific regional EGFP expression pattern, which correlated with the presence of myelin. These results suggest that EGFP expression might be related to the activity of both the CAG promoter and ?-actin in mature retinal neurons and oligodendrocytes. Moreover, EGFP expression might be regulated by light in both immature and adult animals. Since GM are used in numerous retina bioassays, it is essential to know the differential EGFP expression in order to select cells of interest for each study. PMID:25284021

  11. Electroactive biocompatible materials for nerve cell stimulation

    Science.gov (United States)

    Yang, Mei; Liang, Youlong; Gui, Qingyuan; Chen, Jun; Liu, Yong

    2015-04-01

    In the past decades, great efforts have been developed for neurobiologists and neurologists to restore nervous system functions. Recently much attention has been paid to electrical stimulation (ES) of the nervous system as a potential way to repair it. Various conductive biocompatible materials with good electrical conductivity, biocompatibility, and long-term ES or electrical stability have been developed as the substrates for ES. In this review, we summarized different types of materials developed in the purpose for ES of nervous system, including conducting polymers, carbon nanomaterials and composites from conducting polymer/carbon nanomaterials. The present review will give our perspective on the future research directions for further investigation on development of ES particularly on the nerve system.

  12. Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties

    Science.gov (United States)

    Jin, Hua; Yang, Qi; Ji, Feng; Zhang, Ya-jie; Zhao, Yan; Luo, Min

    2015-01-01

    The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as embryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C6 root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C6 brachial plexus injury site (1 × 106 cells/mL, 3 ?L/injection, 25 injections) immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also significantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effectively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals. PMID:25883625

  13. JNK3 involvement in nerve cell apoptosis and neurofunctional recovery after traumatic brain injury?

    OpenAIRE

    Long, Jiang; Cai, Li; Li, Jintao; Zhang, Lei; Yang, Haiyang; Wang, Tinghua

    2013-01-01

    Increasing evidence has revealed that the activation of the JNK pathway participates in apoptosis of nerve cells and neurological function recovery after traumatic brain injury. However, which genes in the JNK family are activated and their role in traumatic brain injury remain unclear. Therefore, in this study, in situ end labeling, reverse transcription-PCR and neurological function assessment were adopted to investigate the alteration of JNK1, JNK2 and JNK3 gene expression in cerebral inju...

  14. Basis for the preferential activation of cardiac sympathetic nerve activity in heart failure

    OpenAIRE

    Ramchandra, Rohit; Hood, Sally G.; Denton, Derek A.; Woods, Robin L.; Mckinley, Michael J.; Mcallen, Robin M.; May, Clive N.

    2009-01-01

    In heart failure (HF), sympathetic nerve activity is increased. Measurements in HF patients of cardiac norepinephrine spillover, reflecting cardiac sympathetic nerve activity (CSNA), indicate that it is increased earlier and to a greater extent than sympathetic activity to other organs. This has important consequences because it worsens prognosis, provoking arrhythmias and sudden death. To elucidate the mechanisms responsible for the activation of CSNA in HF, we made simultaneous direct neura...

  15. An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

    OpenAIRE

    Tang, Zhongshu; Zhang, Shuihua; Lee, Chunsik; KUMAR, Anil; Arjunan, Pachiappan; Li, Yang; Zhang, Fan; Li, Xuri

    2011-01-01

    Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness.

  16. Autonomic nerve activity and atrial fibrillation

    OpenAIRE

    Chen, Peng-sheng; Tan, Alex Y.

    2006-01-01

    This review focuses on the importance of autonomic nervous system (ANS) activity in the induction of paroxysmal atrial fibrillation (PAF). Clinical studies suggest that both sympathetic and parasympathetic nervous systems are important in mediating PAF. Consistent with that hypothesis, heart rate variability analyses showed that sympathovagal imbalance is present before the onset of PAF episodes. The importance of the ANS in PAF is further supported by animal experiments and recent clinical s...

  17. Increased muscle sympathetic nerve activity acutely alters conduit artery shear rate patterns

    OpenAIRE

    Padilla, Jaume; Young, Colin N.; Simmons, Grant H.; Deo, Shekhar H.; Newcomer, Sean C; Sullivan, John P; Laughlin, M. Harold; Fadel, Paul J.

    2010-01-01

    Escalating evidence indicates that disturbed flow patterns, characterized by the presence of retrograde and oscillatory shear stress, induce a proatherogenic endothelial cell phenotype; however, the mechanisms underlying oscillatory shear profiles in peripheral conduit arteries are not fully understood. We tested the hypothesis that acute elevations in muscle sympathetic nerve activity (MSNA) are accompanied by increases in conduit artery retrograde and oscillatory shear. Fourteen healthy men...

  18. GABA-Activated Chloride Channels in Secretory Nerve Endings

    Science.gov (United States)

    Zhang, Shuanglin J.; Jackson, Meyer B.

    1993-01-01

    Neurotransmitters acting on presynaptic terminals regulate synaptic transmission and plasticity. Because of the difficulty of direct electrophysiological recording from small presynaptic terminals, little is known about the ion channels that mediate these actions or about the mechanisms by which transmitter secretion is altered. The patch-clamp technique is used to show that the predominant inhibitory presynaptic neurotransmitter, ?-aminobutyric acid (GABA), activates a GABA_A receptor and gates a chloride channel in the membranes of peptidergic nerve terminals of the posterior pituitary. The opening of a chloride channel by GABA weakly depolarizes the nerve terminal membrane and blocks action potentials. In this way, GABA limits secretion by retarding the spread of excitation into the terminal arborization.

  19. Stromal cell-derived CCL2 drives neuropathic pain states through myeloid cell infiltration in injured nerve.

    Science.gov (United States)

    Van Steenwinckel, Juliette; Auvynet, Constance; Sapienza, Anaïs; Reaux-Le Goazigo, Annabelle; Combadière, Christophe; Melik Parsadaniantz, Stéphane

    2015-03-01

    Neuropathic pain resulting from peripheral nerve injury involves many persistent neuroinflammatory processes including inflammatory chemokines that control leukocyte trafficking and activate resident cells. Several studies have shown that CCL2 chemokine, a potent attractant of monocytes, and its cognate receptor, CCR2, play a critical role in regulating nociceptive processes during neuropathic pain. However, the role of CCL2 in peripheral leukocyte infiltration-associated neuropathic pain remains poorly understood. In particular, the contribution of individual CCL2-expressing cell populations (i.e. stromal and leukocytes) to immune cell recruitment into the injured nerve has not been established. Here, in preclinical model of peripheral neuropathic pain (i.e. chronic constriction injury of the sciatic nerve), we have demonstrated that, CCL2 content was increased specifically in nerve fibers. This upregulation of CCL2 correlated with local monocyte/macrophage infiltration and pain processing. Furthermore, sciatic intraneural microinjection of CCL2 in naïve animals triggered long-lasting pain behavior associated with local monocyte/macrophage recruitment. Using a specific CCR2 antagonist and mice with a CCL2 genetic deletion, we have also established that the CCL2/CCR2 axis drives monocyte/macrophage infiltration and pain hypersensitivity in the CCI model. Finally, specific deletion of CCL2 in stromal or immune cells respectively using irradiated bone marrow-chimeric CCI mice demonstrated that stromal cell-derived CCL2 (in contrast to CCL2 immune cell-derived) tightly controls monocyte/macrophage recruitment into the lesion and plays a major role in the development of neuropathic pain. These findings demonstrate that in chronic pain states, CCL2 expressed by sciatic nerve cells predominantly drove local neuro-immune interactions and pain-related behavior through CCR2 signaling. PMID:25449579

  20. Nerve growth factor rapidly induces ornithine decarboxylase mRNA in PC12 rat pheochromocytoma cells.

    OpenAIRE

    Feinstein, S. C.; Dana, S. L.; Mcconlogue, L.; Shooter, E. M.; Coffino, P.

    1985-01-01

    The mechanism by which nerve growth factor (NGF) stimulates ornithine decarboxylase (OrnDCase; EC 4.1.1.17) activity in the rat pheochromocytoma cell line PC12 was investigated. As demonstrated previously, NGF rapidly induces OrnDCase activity in a dose-dependent manner, with maximal enzymatic activity at 4-6 hr after exposure to NGF. Activity subsequently returns to near basal levels. A cloned OrnDCase cDNA was used to analyze the levels of OrnDCase RNA. In response to NGF administration, Or...

  1. Effects of the potassium channel blocking dendrotoxins on acetylcholine release and motor nerve terminal activity.

    OpenAIRE

    Anderson, A. J.; Harvey, A L

    1988-01-01

    1. The effects of the K+ channel blocking toxins, the dendrotoxins, on neuromuscular transmission and motor nerve terminal activity were assessed on frog cutaneous pectoris, mouse diaphragm and mouse triangularis sterni nerve-muscle preparations. Endplate potentials (e.p.ps) and miniature e.p.ps were recorded with intracellular microelectrodes, and nerve terminal spikes were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves. 2. Dendrotoxin from green mamb...

  2. Are Natural Killer Cells Distributed in Relationship to Nerve Fibers in the Pregnant Mouse Uterus?

    Directory of Open Access Journals (Sweden)

    A.K. Sheikhi

    2007-01-01

    Full Text Available Specialized lymphocytes, called uterine Natural Killer (uNK cells, appear in human and rodent uteri and become abundant at implantation sites during decidualization and early pregnancy. The hallmark of human uNK cells is intense expression of CD56, a neural cell adhesion glycoprotein (NCAM-1 while mature (granulated mouse uNK cells express asialoGM1, a brain ganglioside. Murine uNK cells initiate the normal structural changes induced in maternal spiral arteries by pregnancy but regulation of their recruitment, localization and activation is incompletely understood. To address whether uNK cell distribution is co-localized with nerve fiber distribution, sections of gestation day (gd 6-12 implantation sites from C57BL/6 (B6 mice were studied. Nerve fibers reactive with antibodies to pan neurofilament 150 kD or with tyrosine hydroxylase, an enzyme restricted to sympathetic fibers, were present the walls of branches from the uterine artery in the mesentery. Reactivity was lost as the vessels crossed the myometrium and entered endometrium/decidua. Periodic Acid Schiff’s reactive uNK cells were absent from the mesentery and enriched in decidua basalis where they transcribed NCAM-1 and associated with non-innervated segments of the uterine arteries, including spiral arteries. These data suggest that the localization and activation of mature uNK cells are unlikely to be neurotransmitter regulated.

  3. Nerve growth factor-mediated targeting of liposomes to cells

    International Nuclear Information System (INIS)

    Derivatives of beta-nerve growth factor (NGF), modified by biotinylation of carboxyl groups, were used to target the specific binding of liposomes to cultured rat and human cells bearing NGF receptors. Streptavidin was conjugated via peptide bonds to amino groups on liposomes. Biotinylated NGF, but not unmodified NGF, mediated the binding of radiolabeled streptavidin-liposomes to rat pheochromocytoma PC12 cells in suspension at 40C. In contrast, biotinylated NGF did not increase the binding of hemoglobin-conjugated liposomes tested as a control for specificity. Biotinylated NGF also mediated the specific binding of streptavidin-liposomes containing fluorescein isothiocyanate-labeled dextran to PC12 cells and human melanoma HS294 cells. When HS294 cells were incubated at 370C following liposome binding at 40C, the cell-associated fluorescence appeared to become internalized, in that some cells displayed a perinuclear pattern of fluorescence similar to that observed when lysosomes were stained with acridine orange. Trypsin treatment abolished cell-associated fluorescence when cells were held at 40C but did not affect the fluorescence in cells following incubation at 370C. When liposomes containing carboxyfluorescein, a dye that can diffuse out of acidic compartments, were targeted to HS294 cells, incubation at 370C resulted in diffuse cytoplasmic fluorescence, suggesting that internalized liposomes encounter lysosomal or prelysosomal organelles

  4. Sympathetic nerve activity and whole body heat stress in humans

    OpenAIRE

    Low, David A.; Keller, David M.; Wingo, Jonathan E.; Brothers, R. Matthew; Crandall, Craig G.

    2011-01-01

    We and others have shown that moderate passive whole body heating (i.e., increased internal temperature ?0.7°C) increases muscle (MSNA) and skin sympathetic nerve activity (SSNA). It is unknown, however, if MSNA and/or SSNA continue to increase with more severe passive whole body heating or whether these responses plateau following moderate heating. The aim of this investigation was to test the hypothesis that MSNA and SSNA continue to increase from a moderate to a more severe heat stress....

  5. Activation of the Wnt/?-catenin signaling cascade after traumatic nerve injury.

    Science.gov (United States)

    Kurimoto, S; Jung, J; Tapadia, M; Lengfeld, J; Agalliu, D; Waterman, M; Mozaffar, T; Gupta, R

    2015-05-21

    Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via ?-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and ?-catenin are associated with NMJ destabilization following traumatic denervation. A critical size nerve defect was created by excising a 10-mm segment of the sciatic nerve in mice. Denervated muscles were then harvested at multiple time points for immunofluorescence staining, quantitative real-time PCR, and western blot analysis for Wnt3a and ?-catenin levels. Moreover, a novel Wnt/?-catenin transgenic reporter mouse line was utilized to support our hypothesis of Wnt activation after traumatic nerve injury. The expression of Wnt3a mRNA was significantly increased by 2weeks post-injury and remained upregulated for 2months. Additionally, ?-catenin was activated at 2months post-injury relative to controls. Correspondingly, immunohistochemical analysis of denervated transgenic mouse line TCF/Lef:H2B-GFP muscles demonstrated that the number of GFP-positive cells was increased at the motor endplate band. These collective data support that post-synaptic AChRs destabilize after denervation by a process that involves the Wnt/?-catenin pathway. As such, this pathway serves as a potential therapeutic target to prevent the motor endplate degeneration that occurs following traumatic nerve injury. PMID:25743255

  6. Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells

    OpenAIRE

    Joseph, Nancy M.; Mukouyama, Yoh-suke; Mosher, Jack T.; Jaegle, Martine; Crone, Steven A.; Dormand, Emma-louise; Lee, Kuo-fen; Meijer, Dies; Anderson, David J.; Morrison, Sean J.

    2004-01-01

    Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late gestation but their function is unknown. Current models of nerve development only consider the generation of Schwann cells from neural crest, but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Cre-recombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann cells, were neura...

  7. Elevated intracranial pressure causes optic nerve and retinal ganglion cell degeneration in mice.

    Science.gov (United States)

    Nusbaum, Derek M; Wu, Samuel M; Frankfort, Benjamin J

    2015-07-01

    The purpose of this study was to develop a novel experimental system for the modulation and measurement of intracranial pressure (ICP), and to use this system to assess the impact of elevated ICP on the optic nerve and retinal ganglion cells (RGCs) in CD1 mice. This system involved surgical implantation of an infusion cannula and a radiowave based pressure monitoring probe through the skull and into the subarachnoid space. The infusion cannula was used to increase ICP, which was measured by the probe and transmitted to a nearby receiver. The system provided robust and consistent ICP waveforms, was well tolerated, and was stable over time. ICP was elevated to approximately 30 mmHg for one week, after which we assessed changes in optic nerve structure with transmission electron microscopy in cross section and RGC numbers with antibody staining in retinal flat mounts. ICP elevation resulted in optic nerve axonal loss and disorganization, as well as RGC soma loss. We conclude that the controlled manipulation of ICP in active, awake mice is possible, despite their small size. Furthermore, ICP elevation results in visual system phenotypes of optic nerve and RGC degeneration, suggesting that this model can be used to study the impact of ICP on the visual system. Potentially, this model can also be used to study the relationship between ICP and IOP, as well diseases impacted by ICP variation such as glaucoma, idiopathic intracranial hypertension, and the spaceflight-related visual impairment intracranial pressure syndrome. PMID:25912998

  8. Imaging stretch-activated firing of spinal afferent nerve endings in mouse colon

    Directory of Open Access Journals (Sweden)

    NickSpencer

    2013-10-01

    Full Text Available Spinal afferent neurons play a major role in detecting noxious and innocuous stimuli from visceral organs, such as the gastrointestinal tract. However, all our understanding about spinal afferents has been obtained from recordings of spinal afferent axons, or cell bodies that lie outside the gut wall, or peripheral organ they innervate. No recordings have been made directly from spinal afferent nerve endings, which is where sensory transduction occurs. We developed a preparation whereby recordings could be made from rectal afferent nerve endings in the colon, to characterize mechanisms underlying sensory transduction. Dorsal root ganglia (L6-S2 were removed from mice, whilst retaining neural continuity with the colon. Fluo-4-AM was used to record from rectal afferent nerve endings in myenteric ganglia and circular muscle at 36oC. In slack (unstretched preparations of colon, no calcium transients were recorded from spinal afferent endings. However, in response to a maintained increase in circumferential diameter, a maintained discharge of calcium transients occurred simultaneously in multiple discrete varicosities along single axons of rectal afferents in myenteric ganglia and circular muscle. Stretch-activated calcium transients were resistant to hexamethonium and nifedipine, but were abolished by tetrodotoxin, CPA, BAPTA-AM, cobalt, gadolinium, or replacement of extracellular Na+ with NMDG. In summary, we present a novel preparation in which stretch-activated firing of spinal afferent nerve endings can be recorded, using calcium imaging. We show that circumferential stretch of the colon activates a maintained discharge of calcium transients simultaneously in varicosities along single rectal afferent endings in myenteric ganglia and circular muscle. Non-selective cation channels, TTX-sensitive Na+ channels and both extracellular calcium influx and intracellular Ca2+ stores are required for stretch-activated calcium transients in rectal afferent endings.

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

    Science.gov (United States)

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

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide conduits in the field of nerve tissue engineering. PMID:25580010

  10. Nerve repair with adipose-derived stem cells protects dorsal root ganglia neurons from apoptosis.

    Science.gov (United States)

    Reid, A J; Sun, M; Wiberg, M; Downes, S; Terenghi, G; Kingham, P J

    2011-12-29

    Novel approaches are required in the clinical management of peripheral nerve injuries because current surgical techniques result in deficient sensory recovery. Microsurgery alone fails to address extensive cell death in the dorsal root ganglia (DRG), in addition to poor axonal regeneration. Incorporation of cultured cells into nerve conduits may offer a novel approach in which to combine nerve repair and enhance axonal regeneration with neuroprotective therapies. We examined apoptotic mediator expression in rat DRG neurons following repair of a 10-mm sciatic nerve gap using a novel synthetic conduit made of poly ?-caprolactone (PCL) and primed with adipose-derived stem cells (ADSC) differentiated towards a Schwann cell phenotype or with primary adult Schwann cells. Differentiated ADSC expressed a range of neurotrophic factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and neurotrophin-4 (NT4). Incorporation of either differentiated ADSC or Schwann cells significantly increased anti-apoptotic Bcl-2 mRNA expression (P<0.001) in the DRG, while significantly decreasing pro-apoptotic Bax (P<0.001) and caspase-3 mRNA (P<0.01) expression. Cleaved caspase-3 protein was observed in the DRG following nerve injury which was attenuated when nerve repair was performed using conduits seeded with cells. Cell incorporation into conduit repair of peripheral nerves demonstrates experimental promise as a novel intervention to prevent DRG neuronal loss. PMID:22020320

  11. A systematic evaluation of Schwann cell injection into acellular cold-preserved nerve grafts.

    Science.gov (United States)

    Jesuraj, Nithya J; Santosa, Katherine B; Newton, Piyaraj; Liu, Z; Hunter, Daniel A; Mackinnon, Susan E; Sakiyama-Elbert, Shelly E; Johnson, Philip J

    2011-04-30

    Peripheral nerve regeneration after injury depends on environmental cues and trophic support. Schwann cells (SCs) secrete trophic factors that promote neuronal survival and help guide axons during regeneration. The addition of SCs to acellular nerve grafts is a promising strategy for enhancing peripheral nerve regeneration; however, inconsistencies in seeding parameters have led to varying results. The current work sought to establish a systematic approach to seeding SCs in cold-preserved acellular nerve grafts. Studies were undertaken to (1) determine the needle gauge for optimal cell survival and minimal epineurial disruption during injection, (2) track the seeded SCs using a commercially available dye, and (3) evaluate the seeding efficiency of SCs in nerve grafts. It was determined that seeding with a 27-gauge needle resulted in the highest viability of SCs with the least damage to the epineurium. In addition, Qtracker(®) dye, a commercially available quantum dot nanocrystal, was used to label SCs prior to transplantation, which allowed visualization of the seeded SCs in nerve grafts. Finally, stereological methods were used to evaluate the seeding efficiency of SCs in nerve grafts immediately after injection and following a 1- or 3-day in vitro incubation in SC growth media. Using a systematic approach, the best needle gauge and a suitable dye for SC visualization in acellular nerve grafts were identified. Seeding efficiency in these grafts was also determined. The findings will lead to improvements ability to assess injection of cells (including SCs) for use with acellular nerve grafts to promote nerve regeneration. PMID:21354206

  12. Effect of nerve activity on transport of nerve growth factor and dopamine ?-hydroxylase antibodies in sympathetic neurones

    International Nuclear Information System (INIS)

    The effect of nerve activity on the uptake and retrograde transport of nerve growth factor (NGF) and dopamine ?-hydroxylase (DBH) antibodies was studied by injecting 125I-labelled NGF and anti-DBH into the anterior eye chamber of guinea-pigs. Decentralization of the ipsilateral superior cervical ganglion (SCG) had no significant effect on the retrograde transport of either NGF or anti-DBH. Phenoxybenzamine produced a 50% increase in anti-DBH but not NGF accumulation and this effect was prevented by prior decentralization. This demonstrates that NGF is taken up independently of the retrieval of synaptic vesicle components. (Auth.)

  13. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

    KAUST Repository

    Takaku, Yasuharu

    2014-01-07

    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  14. Nerve growth factor-sensitive S6 kinase in cell-free extracts from PC12 cells

    International Nuclear Information System (INIS)

    Soluble extracts from nerve growth factor (NGF)-stimulated PC12 cells prepared by alkaline lysis show a 2-10 fold increase in the ability to phosphorylate the ribosomal protein S6. The alkaline lysis method yields a preparation of much higher specific activity than does sonication. Half-maximal incorporation of (32P) from (32P)ATP into S6 occurred after 4-7 minutes of nerve growth factor treatment. The partially purified NGF-sensitive S6 kinase has a molecular weight of 45,000 and is not inhibited by the inhibitor of cAMP-dependent protein kinase, NaCl, or trifluoperazine, nor is it activated by the addition of diolein plus phosphatidylserine. Trypsin treatment of either crude extracts or partially purified S6 kinase from control or NGF-treated cells was without effect. These data suggest that the S6 kinase stimulated by NGF is neither cAMP-dependent protein kinase, protein kinase C, nor the result of proteolytic activation of an inactive proenzyme. Treatment of intact cells with dibutyryl cyclic AMP or 5'-N-ethylcarboxamideadenosine also increases the subsequent cell-free phosphorylation of S6. But the effect of NGF in increasing S6 kinase activity cannot be mimicked by treatment of control extract with cAMP-dependent protein kinase in vitro. Thus, it is unlikely to result from the phosphorylation of a less active form of the S6 kinase by a cAMP-dependent protein kinase

  15. Stem cell-based approaches to improve nerve regeneration: potential implications for reconstructive transplantation?

    Science.gov (United States)

    Khalifian, Saami; Sarhane, Karim A; Tammia, Markus; Ibrahim, Zuhaib; Mao, Hai-Quan; Cooney, Damon S; Shores, Jaimie T; Lee, W P Andrew; Brandacher, Gerald

    2015-02-01

    Reconstructive transplantation has become a viable option to restore form and function after devastating tissue loss. Functional recovery is a key determinant of overall success and critically depends on the quality and pace of nerve regeneration. Several molecular and cell-based therapies have been postulated and tested in pre-clinical animal models to enhance nerve regeneration. Schwann cells remain the mainstay of research focus providing neurotrophic support and signaling cues for regenerating axons. Alternative cell sources such as mesenchymal stem cells and adipose-derived stromal cells have also been tested in pre-clinical animal models and in clinical trials due to their relative ease of harvest, rapid expansion in vitro, minimal immunogenicity, and capacity to integrate and survive within host tissues, thereby overcoming many of the challenges faced by culturing of human Schwann cells and nerve allografting. Induced pluripotent stem cell-derived Schwann cells are of particular interest since they can provide abundant, patient-specific autologous Schwann cells. The majority of experimental evidence on cell-based therapies, however, has been generated using stem cell-seeded nerve guides that were developed to enhance nerve regeneration across "gaps" in neural repair. Although primary end-to-end repair is the preferred method of neurorrhaphy in reconstructive transplantation, mechanistic studies elucidating the principles of cell-based therapies from nerve guidance conduits will form the foundation of further research employing stem cells in end-to-end repair of donor and recipient nerves. This review presents key components of nerve regeneration in reconstructive transplantation and highlights the pre-clinical studies that utilize stem cells to enhance nerve regeneration. PMID:25428664

  16. Senescent Cells Impair Erectile Function through Induction of Endothelial Dysfunction and Nerve Injury in Mice

    Science.gov (United States)

    Saito, Yasuho; Niimi, Aya; Nomiya, Akira; Fukuhara, Hiroshi; Kume, Haruki; Homma, Yukio

    2015-01-01

    Erectile dysfunction (ED) is a major health problem, particularly in the elderly population, which is rapidly increasing. It is necessary to elucidate the mechanism by which ED occurs in the elderly. Cellular senescence is commonly detected in old tissues, and it is well known that senescent cells not only withdraw from the cell cycle but also remain viable and actively produce a variety of cytokines. We examined the effect of senescent cells on erectile function after injection of senescent cells into the penises of mice. Human umbilical vein endothelial cells were infected with an adenovirus expressing a constitutively active mutant of Ras to induce senescence, and were injected into the penises of nude mice. These senescent cells expressed proinflammatory cytokines such as interleukin-1? (IL-1?). Injection of senescent cells impaired erectile function, as assessed by the measurement of intracavernous pressure. Although the structure of the cavernous body did not remarkably change, expression of the catalytically active form of endothelial nitric oxide synthase and that of total neural nitric oxide synthase significantly decreased after injection. The penises injected with the senescent cells expressed human IL-1? and subsequently endogenous proinflammatory cytokines such as mouse IL-1? and tumor necrosis factor-?. These results suggested that senescent cells impaired erectile function through induction of endothelial dysfunction and nerve injury. These effects may be mediated by proinflammatory cytokines produced by senescent cells. PMID:25894557

  17. A Systematic Evaluation of Schwann Cell Injection into Acellular Cold-Preserved Nerve Grafts

    OpenAIRE

    Jesuraj, Nithya J.; Santosa, Katherine B.; Newton, Piyaraj; Liu, Z.; Hunter, Daniel A; Mackinnon, Susan E.; Sakiyama-Elbert, Shelly E; Philip J. Johnson

    2011-01-01

    Peripheral nerve regeneration after injury depends on environmental cues and trophic support. Schwann cells (SCs) secrete trophic factors that promote neuronal survival and help guide axons during regeneration. The addition of SCs to acellular nerve grafts is a promising strategy for enhancing peripheral nerve regeneration; however, inconsistencies in seeding parameters have led to varying results. The current work sought to establish a systematic approach to seeding SCs in cold-preserved ace...

  18. GDF11 Forms a Bone Morphogenetic Protein 1-Activated Latent Complex That Can Modulate Nerve Growth Factor-Induced Differentiation of PC12 Cells

    Science.gov (United States)

    Ge, Gaoxiang; Hopkins, Delana R.; Ho, Wen-Bin; Greenspan, Daniel S.

    2005-01-01

    All transforming growth factor ? (TGF-?) superfamily members are synthesized as precursors with prodomain sequences that are proteolytically removed by subtilisin-like proprotein convertases (SPCs). For most superfamily members, this is believed sufficient for activation. Exceptions are TGF-?s 1 to 3 and growth differentiation factor 8 (GDF8), also known as myostatin, which form noncovalent, latent complexes with their SPC-cleaved prodomains. Sequence similarities between TGF-?s 1 to 3, myostatin, and superfamily member GDF11, also known as bone morphogenetic protein 11 (BMP11), prompted us to examine whether GDF11 might be capable of forming a latent complex with its cleaved prodomain. Here we demonstrate that GDF11 forms a noncovalent latent complex with its SPC-cleaved prodomain and that this latent complex is activated via cleavage at a single specific site by members of the developmentally important BMP1/Tolloid family of metalloproteinases. Evidence is provided for a molecular model whereby formation and activation of this complex may play a general role in modulating neural differentiation. In particular, mutant GDF11 prodomains impervious to cleavage by BMP1/Tolloid proteinases are shown to be potent stimulators of neurodifferentiation, with potential for therapeutic applications. PMID:15988002

  19. Nardosinone, a novel enhancer of nerve growth factor in neurite outgrowth from PC12D cells.

    Science.gov (United States)

    Li, P; Matsunaga, K; Yamamoto, K; Yoshikawa, R; Kawashima, K; Ohizumi, Y

    1999-09-24

    We isolated nardosinone as a neuritogenic substance from Nardostachys chinensis. Nardosinone did not exhibit the neurotrophic activity but caused a marked enhancement of the nerve growth factor (NGF)-mediated neurite outgrowth from PC12D cells. Nardosinone-induced enhancement of the NGF-action was completely blocked by PD98059, a representative mitogen activated protein kinase (MAPK) kinase inhibitor. The microscopic observations indicated that the neurites in response to nardosinone and NGF were quite long and were generally extended to the neighboring cells. These results suggest that nardosinone enhances the NGF-induced neurite outgrowth from PC12D cells probably by amplifying an up-stream step of MAPK kinase in the NGF receptor-mediated intracellular signaling pathway. PMID:10505650

  20. Binding and internalization of nerve growth factor by PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kasaian, M.T.

    1987-01-01

    The interaction of nerve growth factor (NGF) with its cell surface receptors has been studied using both fluorescent- and radio-labelled NGF. The fluorescence studies were done by flow cytometry, and gave information about the concentration dependence and time course of NGF binding to rat pheochromocytoma cells (PC12) and human melanoma cells (A875). /sup 125/I-NGF was used to study the fate of NGF in PC12 cells following its association with cell surface receptors. Variations of the PC12 binding assay were used to distinguish ligand bound to fast and slowly dissociating receptors at the cell surface, internalized ligand, and cytoskeletally-associated NGF. Ligand uptake into each of these pools was followed in untreated cells, as well as in cells exposed to colchicine and/or cytochalasin B to disrupt the cytoskeleton. NGF degradation was also followed in these cells, and chloroquine was used to inhibit this process. In a separate project, NGF activity was assayed in samples of human amniotic fluid and cerebrospinal fluid (CSF). A range of activities was found in these samples, with the CSF samples containing somewhat more activity than the amniotic fluid samples.

  1. Laser-activated protein solder for peripheral nerve repair

    Science.gov (United States)

    Trickett, Rodney I.; Lauto, Antonio; Dawes, Judith M.; Owen, Earl R.

    1995-05-01

    A 100 micrometers core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the albumin based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 +/- 5 min. (n equals 20) compared to 23 +/- 9 min. (n equals 10) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 +/- 5 g, while microsutured nerves had a tensile strength of 40 +/- 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study is under way comparing laser solder repaired tibial nerves to conventional microsuture repair. At the time of submission 15 laser soldered nerves and 7 sutured nerves were characterized at 3 months and showed successful regeneration with compound muscle action potentials of 27 +/- 8 mV and 29 +/- 8 mW respectively. A faster, less damaging and long lasting laser based anastomotic technique is presented.

  2. Senescence in adipose-derived stem cells and its implications in nerve regeneration

    OpenAIRE

    Mantovani, Cristina; Terenghi, Giorgio; Magnaghi, Valerio

    2014-01-01

    Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-derived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process w...

  3. BD™ PuraMatrix™ peptide hydrogel seeded with Schwann cells for peripheral nerve regeneration.

    Science.gov (United States)

    McGrath, Aleksandra M; Novikova, Liudmila N; Novikov, Lev N; Wiberg, Mikael

    2010-10-30

    This study investigated the effects of a membrane conduit filled with a synthetic matrix BD™ PuraMatrix™ peptide (BD) hydrogel and cultured Schwann cells on regeneration after peripheral nerve injury in adult rats. After sciatic axotomy, a 10mm gap between the nerve stumps was bridged using ultrafiltration membrane conduits filled with BD hydrogel or BD hydrogel containing Schwann cells. In control experiments, the nerve defect was bridged using either membrane conduits with alginate/fibronectin hydrogel or autologous nerve graft. Axonal regeneration within the conduit was assessed at 3 weeks and regeneration of spinal motoneurons and recovery of muscle weight evaluated at 16 weeks postoperatively. Schwann cells survived in the BD hydrogel both in culture and after transplantation into the nerve defect. Regenerating axons grew significantly longer distances within the conduits filled with BD hydrogel when compared with the alginate/fibronectin hydrogel and alginate/fibronectin with Schwann cells. Addition of Schwann cells to the BD hydrogel considerably increased regeneration distance with axons crossing the injury gap and entering into the distal nerve stump. The conduits with BD hydrogel showed a linear alignment of nerve fibers and Schwann cells. The number of regenerating motoneurons and recovery of the weight of the gastrocnemius muscle was inferior in BD hydrogel and alginate/fibronectin groups compared with nerve grafting. Addition of Schwann cells did not improve regeneration of motoneurons or muscle recovery. The present results suggest that BD hydrogel with Schwann cells could be used within biosynthetic conduits to increase the rate of axonal regeneration across a nerve defect. PMID:20633614

  4. Nestin-Expressing Stem Cells Promote Nerve Growth in Long-Term 3-Dimensional Gelfoam®-Supported Histoculture

    OpenAIRE

    Mii, Sumiyuki; Uehara, Fuminari; Yano, Shuya; Tran, Benjamin; Miwa, Shinji; Hiroshima, Yukihiro; Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M.

    2013-01-01

    We have previously reported that hair follicles contain multipotent stem cells which express nestin. The nestin-expressing cells form the hair follicle sensory nerve. In vitro, the nestin-expressing hair follicle cells can differentiate into neurons, Schwann cells, and other cell types. In the present study, the sciatic nerve was excised from transgenic mice in which the nestin promoter drives green fluorescent protein (ND-GFP mice). The ND-GFP cells of the sciatic nerve were also found to be...

  5. Effects of renal sympathetic nerve radiofrequency ablation on norepinephrine spillover rate and sympathetic nerve activity in dogs with hypertension

    Directory of Open Access Journals (Sweden)

    Hang YU

    2012-11-01

    Full Text Available Objective ?To evaluate the validity and explore the mechanism of renal sympathetic denervation (RSD in the treatment of dogs with hypertension reproduced by constriction of abdominal aorta. Methods ?The hypertension model was reproduced by constriction of abdominal aorta in 20 adult healthy dogs. These dogs were then randomly divided into the treatment group and control group (10 each. Renal sympathetic nerve radiofrequency ablation was done in treatment group 1 month after modeling. The foreleg blood pressure, sympathetic activity and norepinephrine overflow rate of dogs in two groups were detected before modeling, and 1, 2 and 3 months after modeling, and the trend of the change was also observed. Results ?One month after modeling, the systolic blood pressure (SBP, diastolic blood pressure (DBP and mean arterial blood pressure (MAP were elevated significantly in control group (146.7±21.0, 89.0±12.7 and 108.3±14.9mmHg compared with those before modeling (119.5±13.2, 76.5±7.8 and 90.9±8mmHg, P < 0.05. The renal sympathetic activity impulse and norepinephrine spillover rate were also enhanced significantly (P < 0.05. The renal sympathetic nerve activity obviously decreased in the treatment group after the operation, and then increased 2 months after the ablation. The norepinephrine spillover rate in treatment group increased significantly 1 month after modeling (P < 0.05, and decreased after ablation, and it lasted to the end of the experiment (P < 0.05. One and two months after ablation, the norepinephrine spillover rate was lower in treatment group than in control group (P < 0.05. Conclusion ?Renal sympathetic nerve radiofrequency ablation significantly inhibits the elevation of norepinephrine spillover rate and sympathetic nerve activity in dogs with hypertension.

  6. Laser-activated protein bands for peripheral nerve repair

    Science.gov (United States)

    Lauto, Antonio; Trickett, Rodney I.; Malik, Richard; Dawes, Judith M.; Owen, Earl R.

    1996-01-01

    A 100 micrometer core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the protein based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 plus or minus 5 min. (n equals 24) compared to 23 plus or minus 9 min (n equals 13) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 plus or minus 5 g, while microsutured nerves had a tensile strength of 40 plus or minus 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study, with a total of fifty-seven adult male wistar rats, compared laser solder repaired tibial nerves to conventional microsuture repair. Twenty-four laser soldered nerves and thirteen sutured nerves were characterized at three months and showed successful regeneration with average compound muscle action potentials (CMAP) of 2.4 plus or minus 0.7 mV and 2.7 plus or minus 0.8 mV respectively. Histopathology of the in vivo study, confirmed the comparable regeneration of axons in laser and suture operated nerves. A faster, less damaging and long lasting laser based anastomotic technique is presented.

  7. Stem cell therapy for central nerve system injuries: glial cells hold the key

    OpenAIRE

    Xiao, Li; Saiki, Chikako; Ide, Ryoji

    2014-01-01

    Mammalian adult central nerve system (CNS) injuries are devastating because of the intrinsic difficulties for effective neuronal regeneration. The greatest problem to be overcome for CNS recovery is the poor regeneration of neurons and myelin-forming cells, oligodendrocytes. Endogenous neural progenitors and transplanted exogenous neuronal stem cells can be the source for neuronal regeneration. However, because of the harsh local microenvironment, they usually have very low efficacy for funct...

  8. Tetramethylpyrazine protects Schwann cells from ischemia-like injury and increases cell survival in cold ischemic rat nerves

    Scientific Electronic Library Online (English)

    Ming-Ming, Yang; Wei, Huang; Dian-Ming, Jiang.

    2015-03-01

    Full Text Available Tetrametilpirazina (TMP), o principal componente do extrato de Ligusticum wallichi Franchat (erva chinesa), apresenta propriedades neuroprotetoras na isquemia. Nesse estudo, avaliamos seus efeitos protetores nas células de Schwann (SC), cultivando-as na presença de condições de depleção de oxigênio [...] da glicose (OGD) e medindo a sobrevivência dos nervos de ratos isquêmicos pelo resfriamento. No modelo de lesão isquêmica em SC induzida por OGD, demonstramos que o tratamento com TMP não somente reduziu as perdas de viabilidade celular induzida por OGD, a morte celular, a apoptose de SC dose-dependente e inibiu a liberação de LDH, mas, também, suprimiu a infra-regulação do Vcl-2 e a supra-regulação de Bax e caspase-3, e inibiu a consequente ativação da caspase-3. No modelo de nervo isquêmico por resfriamento, observamos que a exposição prolongada ao resfriamento por quatro semanas estava, marcadamente, associada com a ausência de SC, com o decréscimo da viabilidade celular e a apoptose em segmentos de nervo incubados na solução da Universidade de Wisconsin apenas. Entretanto, a TMP atenuou o dano no segmento do nervo preservando SC e antagonizando a diminuição da viabilidade da fibra nervosa e o aumento das células TUNEL-positiva de modo dose-dependente. De forma conjunta, nossos resultados indicam que o TMP não só fornece efeitos protetores em um modelo de dano semelhante à isquemia de SC de ratos cultivados pela regulação de BCl-2, Bax e caspase 3, mas, também, aumenta a sobrevivência celular e suprime a apoptose no modelo de isquemia por resfriamento por exposição prolongada por quatro semanas. Então, TMP pode ser uma estratégia terapêutica eficaz para prevenir doenças isquêmicas do sistema nervoso periférico e melhora a armazenagem do nervo periférico. Abstract in english Tetramethylpyrazine (TMP), a major active ingredient of Ligusticum wallichi Franchat extract (a Chinese herb), exhibits neuroprotective properties in ischemia. In this study, we assessed its protective effects on Schwann cells (SCs) by culturing them in the presence of oxygen glucose deprivation (OG [...] D) conditions and measuring cell survival in cold ischemic rat nerves. In the OGD-induced ischemic injury model of SCs, we demonstrated that TMP treatment not only reduced OGD-induced cell viability losses, cell death, and apoptosis of SCs in a dose-dependent manner, and inhibited LDH release, but also suppressed OGD-induced downregulation of Bcl-2 and upregulation of Bax and caspase-3, as well as inhibited the consequent activation of caspase-3. In the cold ischemic nerve model, we found that prolonged cold ischemic exposure for four weeks was markedly associated with the absence of SCs, a decrease in cell viability, and apoptosis in preserved nerve segments incubated in University of Wisconsin solution (UWS) alone. However, TMP attenuated nerve segment damage by preserving SCs and antagonizing the decrease in nerve fiber viability and increase in TUNEL-positive cells in a dose-dependent manner. Collectively, our results indicate that TMP not only provides protective effects in an ischemia-like injury model of cultured rat SCs by regulating Bcl-2, Bax, and caspase-3, but also increases cell survival and suppresses apoptosis in the cold ischemic nerve model after prolonged ischemic exposure for four weeks. Therefore, TMP may be a novel and effective therapeutic strategy for preventing peripheral nervous system ischemic diseases and improving peripheral nerve storage.

  9. Both central command and exercise pressor reflex activate cardiac sympathetic nerve activity in decerebrate cats

    OpenAIRE

    Tsuchimochi, Hirotsugu; Hayes, Shawn G.; Mccord, Jennifer L.; Kaufman, Marc P.

    2009-01-01

    Both static and dynamic exercise are known to increase cardiac pump function as well as arterial blood pressure. Feedforward control by central command and feedback control by the exercise pressor reflex are thought to be the neural mechanisms causing these effects during exercise. It remains unknown as to how each mechanism activates cardiac sympathetic nerve activity (CSNA) during exercise, especially at its onset. Thus we examined the response of CSNA to stimulation of the mesencephalic lo...

  10. Surgical treatment options and management strategies of metastatic renal cell carcinoma to the lumbar spinal nerve roots

    OpenAIRE

    Strong, Christian; Yanamadala, Vijay; Khanna, Arjun; Walcott, Brian P.; Nahed, Brian V.; Borges, Lawrence F.; Coumans, Jean-valery C. E.

    2013-01-01

    Spinal nerve root metastasis of renal cell carcinoma is a rare occurrence. In addition to treatment of the primary lesion, surgical resection of the nerve root metastasis, occasionally with sacrifice of the involved nerve, is the accepted standard of treatment. Resection often resolves presenting motor and pain symptoms due to relief of neural compression. We describe two patients with nerve root metastasis of renal cell carcinoma and their management. While locally advanced and metastatic re...

  11. Regulation of muscle sympathetic nerve activity after bed rest deconditioning

    Science.gov (United States)

    Pawelczyk, J. A.; Zuckerman, J. H.; Blomqvist, C. G.; Levine, B. D.

    2001-01-01

    Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.

  12. Effects of the potassium channel blocking dendrotoxins on acetylcholine release and motor nerve terminal activity.

    Science.gov (United States)

    Anderson, A J; Harvey, A L

    1988-01-01

    1. The effects of the K+ channel blocking toxins, the dendrotoxins, on neuromuscular transmission and motor nerve terminal activity were assessed on frog cutaneous pectoris, mouse diaphragm and mouse triangularis sterni nerve-muscle preparations. Endplate potentials (e.p.ps) and miniature e.p.ps were recorded with intracellular microelectrodes, and nerve terminal spikes were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves. 2. Dendrotoxin from green mamba (Dendroaspis angusticeps) venom and toxin I from black mamba (D. polylepis) venom increased the amplitude of e.p.ps by increasing quantal content, and also induced repetitive e.p.ps. 3. Perineural recordings revealed that dendrotoxins could decrease the component of the waveform associated with K+ currents at the nerve terminals, and induce repetitive activation of nerve terminals. 4. In frog motor nerves, dendrotoxins are known to block the fast f1 component of the K+ current at nodes of Ranvier. Blockade of a similar component of the K+ current at motor nerve terminals may be responsible for the effects of these toxins on neuromuscular transmission. 5. Similar conclusions can be drawn from the results obtained from mouse neuromuscular junctions. PMID:2450611

  13. A comparison between complete immobilisation and protected active mobilisation in sensory nerve recovery following isolated digital nerve injury.

    LENUS (Irish Health Repository)

    Henry, F P

    2012-06-01

    Post-operative immobilisation following isolated digital nerve repair remains a controversial issue amongst the microsurgical community. Protocols differ from unit to unit and even, as evidenced in our unit, may differ from consultant to consultant. We undertook a retrospective review of 46 patients who underwent isolated digital nerve repair over a 6-month period. Follow-up ranged from 6 to 18 months. Twenty-four were managed with protected active mobilisation over a 4-week period while 22 were immobilised over the same period. Outcomes such as return to work, cold intolerance, two-point discrimination and temperature differentiation were used as indicators of clinical recovery. Our results showed that there was no significant difference noted in either clinical assessment of recovery or return to work following either post-operative protocol, suggesting that either regime may be adopted, tailored to the patient\\'s needs and resources of the unit.

  14. Long-term efficacy and safety outcomes of transplantation of induced pluripotent stem cell-derived neurospheres with bioabsorbable nerve conduits for peripheral nerve regeneration in mice.

    Science.gov (United States)

    Uemura, Takuya; Ikeda, Mikinori; Takamatsu, Kiyohito; Yokoi, Takuya; Okada, Mitsuhiro; Nakamura, Hiroaki

    2014-01-01

    The induced pluripotent stem cell (iPSc) offers great potential for cell-based therapy in regenerative medicine. We previously developed tissue-engineered bioabsorbable nerve conduits coated with iPSc-derived neurospheres for use in peripheral nerve repair. Here, we examine the long-term efficacy and safety of using nerve conduits with iPSc technology for peripheral nerve repair in mice. The nerve conduit consisted of an outer layer of a poly L-lactide mesh and an inner layer of porous sponge composed of 50% L-lactide and 50% ?-caprolactone. Secondary neurospheres were derived from mouse iPScs, resuspended and cultured within the conduit for 14 days. Conduits were implanted within surgically administered 5-mm defects in the left sciatic nerve of mice (iPSc group; n = 14). The defects in the control group (n = 13) were reconstructed using the nerve conduit alone. At 4, 8, 12, 24 and 48 weeks postsurgery, motor and sensory functional recovery in the iPSc group had improved significantly more than in the control group. At 24 and 48 weeks, histological analysis revealed axonal regeneration in the nerve conduits of both groups. However, axonal regeneration and myelination were significantly enhanced in the iPSc group. No teratomas were identified in the iPSc group at any time point. Therefore, we here demonstrate that bioabsorbable nerve conduits coated with iPSc-derived neurospheres promote enhanced regeneration of peripheral nerves and functional recovery without teratoma formation in the long term. This combination of iPSc technology and bioabsorbable nerve conduits has the potential to be a safe future tool for the treatment of peripheral nerve defects. © 2015 S. Karger AG, Basel. PMID:25823624

  15. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karadag, Demet; Karaguelle, Ayse Tuba; Erden, Ilhan; Erden, Ayse E-mail: erden@ada.net.tr

    2002-10-01

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment.

  16. Stem cell therapy for central nerve system injuries: glial cells hold the key

    Science.gov (United States)

    Xiao, Li; Saiki, Chikako; Ide, Ryoji

    2014-01-01

    Mammalian adult central nerve system (CNS) injuries are devastating because of the intrinsic difficulties for effective neuronal regeneration. The greatest problem to be overcome for CNS recovery is the poor regeneration of neurons and myelin-forming cells, oligodendrocytes. Endogenous neural progenitors and transplanted exogenous neuronal stem cells can be the source for neuronal regeneration. However, because of the harsh local microenvironment, they usually have very low efficacy for functional neural regeneration which cannot compensate for the loss of neurons and oligodendrocytes. Glial cells (including astrocytes, microglia, oligodendrocytes and NG2 glia) are the majority of cells in CNS that provide support and protection for neurons. Inside the local microenvironment, glial cells largely influence local and transplanted neural stem cells survival and fates. This review critically analyzes current finding of the roles of glial cells in CNS regeneration, and highlights strategies for regulating glial cells’ behavior to create a permissive microenvironment for neuronal stem cells. PMID:25221575

  17. M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

    Science.gov (United States)

    Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

    2015-05-01

    Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients. PMID:25772973

  18. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    International Nuclear Information System (INIS)

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na+-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  19. Fabrication of bioactive conduits containing the fibroblast growth factor 1 and neural stem cells for peripheral nerve regeneration across a 15 mm critical gap

    International Nuclear Information System (INIS)

    Nerve conduits are often used in combination with bioactive molecules and stem cells to enhance peripheral nerve regeneration. In this study, the acidic fibroblast growth factor 1 (FGF1) was immobilized onto the microporous/micropatterned poly (D, L-lactic acid) (PLA) nerve conduits after open air plasma treatment. PLA substrates grafted with chitosan in the presence of a small amount of gold nanoparticles (nano Au) showed a protective effect on the activity of the immobilized FGF1 in vitro. Different conduits were tested for their ability to bridge a 15 mm critical gap defect in a rat sciatic nerve injury model. Axon regeneration and functional recovery were evaluated by histology, walking track analysis and electrophysiology. Among different conduits, PLA conduits grafted with chitosan–nano Au and the FGF1 after plasma activation had the greatest regeneration capacity and functional recovery in the experimental animals. When the above conduit was seeded with aligned neural stem cells, the efficacy was further enhanced and it approached that of the autograft group. This work suggested that microporous/micropatterned nerve conduits containing bioactive growth factors may be successfully fabricated by micropatterning techniques, open plasma activation, and immobilization, which, combined with aligned stem cells, may synergistically contribute to the regeneration of the severely damaged peripheral nerve. (paper)

  20. The plasminogen activator system modulates sympathetic nerve function

    OpenAIRE

    Schaefer, Ulrich; Machida, Takuji; Vorlova, Sandra; Strickland, Sidney; Levi, Roberto

    2006-01-01

    Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but wa...

  1. Signet ring cell adenocarcinoma and bilateral leptomeningeal involvement of optic nerve sheaths.

    Science.gov (United States)

    Mbekeani, Joyce N; Haseeb, Mohammed Q; Tulbah, Asma M; Hamed, Salem H; Al Hazzaa, Selwa A; Dogar, Mohammad A

    2015-06-01

    Signet ring cell adenocarcinoma has a propensity for leptomeningeal carcinomatosis, and although bilateral optic nerve involvement is rare, this may occur with or without obvious signs of diffuse leptomeningeal involvement. We describe a 41-year-old woman who presented with a brief history of simultaneous bilateral visual deterioration and a distended abdomen. Examination revealed bilateral no light perception vision and bilateral optic disc edema. Radiologic work-up showed large multiple pelvic masses involving the ovaries, multifocal boney deposits, and widespread central nervous system carcinomatosis, involving the optic nerves and the first, fifth, and eighth cranial nerves. Biopsy of an ovarian mass demonstrated islands of signet ring cells. Signet cell adenocarcinomatous infiltration of the leptomeningeal space should be considered in cases of bilateral simultaneous vision loss with signs suggestive of leptomeningeal infiltration of the optic nerve sheath. PMID:25839780

  2. Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in Schwann cells through purinergic signaling and the PKC-PKD pathway.

    Science.gov (United States)

    Xu, Pin; Rosen, Kenneth M; Hedstrom, Kristian; Rey, Osvaldo; Guha, Sushovan; Hart, Courtney; Corfas, Gabriel

    2013-07-01

    Upon peripheral nerve injury, specific molecular events, including increases in the expression of selected neurotrophic factors, are initiated to prepare the tissue for regeneration. However, the mechanisms underlying these events and the nature of the cells involved are poorly understood. We used the injury-induced upregulation of glial cell-derived neurotrophic factor (GDNF) expression as a tool to gain insights into these processes. We found that both myelinating and nonmyelinating Schwann cells are responsible for the dramatic increase in GDNF expression after injury. We also demonstrate that the GDNF upregulation is mediated by a signaling cascade involving activation of Schwann cell purinergic receptors, followed by protein kinase C signaling which activates protein kinase D (PKD), which leads to increased GDNF transcription. Given the potent effects of GDNF on survival and repair of injured peripheral neurons, we propose that targeting these pathways may yield therapeutic tools to treat peripheral nerve injury and neuropathies. PMID:23553603

  3. Efficiency of laryngeal motor nerve repair is greater with bulbar than with mucosal olfactory ensheathing cells.

    Science.gov (United States)

    Paviot, Alexandre; Guérout, Nicolas; Bon-Mardion, Nicolas; Duclos, Célia; Jean, Laetitia; Boyer, Olivier; Marie, Jean-Paul

    2011-03-01

    The real ability of OECs provided by olfactory mucosa cultures (OM-OECs) and those from olfactory bulb cultures (OB-OECs) must be better characterized in order to propose their future clinical application. Therefore, we used a lesion of the vagus nerve (VN), which constitutes a severe motor denervation due to long distance of the muscular targets (4.5 cm). We performed a section/anastomosis surgery of the VN, at the third tracheal ring. Then, OM-OECs and OB-OECs were injected in matrigel around the lesion site. Three months after surgery, laryngeal muscle activity, synkinesis phenomena and latency were evaluated by videolaryngoscopy and electromyography recordings. To complete these procedures, axonal morphometric study of the right recurrent nerve was performed to assess axonal regrowth and tracking of green fluorescent protein positive cells was performed. Recurrent nerve is the motor branch innervating the laryngeal muscles, and is located distally to the lesion, near the muscular targets (0.7 cm). These analyses permitted to compare the ability of these two populations to improve functional recovery and axonal regrowth. Our results show that, OM-OECs improved electrical muscular activity and nervous conduction with significant tissue healing but induced aberrant movement and poor functional recovery. In contrast, OB-OECs induced a partial functional recovery associated with an increase in the number of myelinated fibers and nervous conduction. Our study suggests that, as recently reported in a microarray study, OM-OECs and OB-OECs express different properties. In particular, OM-OECs could regulate inflammation processes and extracellular matrix formation but have a poor regeneration potential, whereas, OB-OECs could improve functional recovery by inducing targeted axonal regrowth. PMID:21168497

  4. Biologic strategies to improve nerve regeneration after peripheral nerve repair.

    Science.gov (United States)

    Fowler, John R; Lavasani, Mitra; Huard, Johnny; Goitz, Robert J

    2015-05-01

    Background?Peripheral nerve injuries remain a challenging problem for microsurgeons. Direct repair is the gold standard, but often the surgeon is left with a gap that prevents tension-free repair. The use of empty tubes/conduits/allograft has resulted in regeneration of some sensory and motor function, but the results remain suboptimal compared with autograft. However, the use of nerve autograft has associated donor site morbidity and limited availability. Methods?A review of the literature was performed to determine current biologic strategies to improve nerve regeneration after nerve repair. Results?Nerve conduits, various neurotrophic factors, and stem cells are currently being studied as alternatives to the use of nerve autograft. Conclusions?Sensory and motor recovery after peripheral nerve regeneration remains suboptimal, especially in cases where primary nerve repair is not possible. Current strategies to augment nerve regeneration have focused on modulating the presence and activity of Schwann cells, either through direct implantation or by stimulating stem cells to differentiate toward Schwann cells, and through the use of neurotrophic factors to enhance the speed and quality of axon growth. Clinical studies will be necessary to determine the benefit of these strategies. PMID:25503421

  5. A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells

    Science.gov (United States)

    Jenkins, Phillip M.; Laughter, Melissa R.; Lee, David J.; Lee, Young M.; Freed, Curt R.; Park, Daewon

    2015-06-01

    Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension.

  6. A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells.

    Science.gov (United States)

    Jenkins, Phillip M; Laughter, Melissa R; Lee, David J; Lee, Young M; Freed, Curt R; Park, Daewon

    2015-12-01

    Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension. PMID:26071111

  7. Olfactory Nerve–Evoked, Metabotropic Glutamate Receptor–Mediated Synaptic Responses in Rat Olfactory Bulb Mitral Cells

    OpenAIRE

    Ennis, Matthew; Zhu, Mingyan; Heinbockel, Thomas; Hayar, Abdallah

    2006-01-01

    The group I metabotropic glutamate receptor (mGluR) subtype, mGluR1, is highly expressed on the apical dendrites of olfactory bulb mitral cells and thus may be activated by glutamate released from olfactory nerve (ON) terminals. Previous studies have shown that mGluR1 agonists directly excite mitral cells. In the present study, we investigated the involvement of mGluR1 in ON-evoked responses in mitral cells in rat olfactory bulb slices using patch-clamp electrophysiology. In voltage-clamp rec...

  8. Early gene regulation by nerve growth factor in PC12 cells: induction of an interferon-related gene.

    OpenAIRE

    Tirone, F.; Shooter, E. M.

    1989-01-01

    Nerve growth factor (NGF) induces the chromaffin cell line PC12 to differentiate into cells with many of the properties of sympathetic neurons. We investigated the early differentiative phase and identified a gene, PC4, rapidly and transiently induced by NGF in PC12 cells. PC4 cDNA is homologous to the partial sequence of a putative mouse beta-interferon and encodes a protein related to a lymphokine, the rat gamma-interferon protein. Nonetheless, PC4 appears devoid of antiviral activity. PC4 ...

  9. Evaluation of Na+/K+ pump function following repetitive activity in mouse peripheral nerve

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Krarup, Christian

    2006-01-01

    After conduction of prolonged trains of impulses the increased Na+/K+ pump activity leads to hyperpolarization. The aim of this study was to develop a mouse model to investigate the Na+/K+ pump function in peripheral nerve by measuring the decrease in excitability during activity-dependent hyperpolarization. Acute electrophysiological investigations were carried out in seven adult mice. Nerve excitability was evaluated by tracking the change in threshold current after 5 min of 100 Hz stimulation of the tibial nerve at ankle. We developed a threshold tracking system that allowed us to follow several excitability measures simultaneously from the evoked plantar compound muscle action potential (CMAP) and sciatic compound nerve action potential (CNAP). Three minutes after repetitive supramaximal stimulation maximal CMAP and CNAP amplitudes recovered but the threshold was increased approximately 40% for motor axons approximately 34% for axons generating CNAP. The threshold recovered with a rate of 3.8%/minute thatwas similar for nerve and motor responses. By tracking the effect of polarizing currents we found evidence of activity dependent hyperpolarization, and our data suggest that the observed threshold change after repetitive stimulation of the mouse tibial nerve is an indicator of the Na+/K+ pump function in vivo. Evaluation of activity-dependent hyperpolarization may be an important indicator of axonal ability to cope with Na+ load.

  10. Low birth size and final height predict high sympathetic nerve activity in adulthood.

    OpenAIRE

    Boguszewski, Mc; Johannsson, G.; Fortes, Lc; Sverrisdo?ttir, Yb

    2004-01-01

    OBJECTIVE: Being born small for gestational age (SGA) is associated with insulin resistance, hypertension and increased cardiovascular morbidity/mortality in adulthood. Sympathetic nerve hyperactivity is a well-known risk factor for cardiovascular disease mortality and is proposed to link insulin resistance with hypertension. The objective of this study was to test the hypothesis that sympathetic nerve activity is altered in individuals born SGA. DESIGN: A cross-sectional, comparative study o...

  11. Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells

    International Nuclear Information System (INIS)

    Nerve trauma initiates significant changes in the composition of proteins secreted by nonneuronal cells. The most prominent of these proteins is a 37-kDa protein, whose expression correlates with the time course of nerve development, degeneration, and regeneration. The authors report that the 37-kDa protein is apolipoprotein E (apoE). They produced a specific antiserum against the 37-kDa protein isolated from previously crushed nerves. This antiserum recognizes a 36-kDa protein in rat serum that they have purified and identified as apoE. The anti-37-kDa antiserum also recognizes apoE on electrophoretic transfer blots of authentic samples of high and very low density lipoproteins. The nerve 37-kDa protein comigrates with apoE by two-dimensional electrophoresis, shares a similar amino acid composition, and reacts with an antiserum against authentic apoE. The purified apoE specifically blocks the immunoprecipitation of [35S]methionine-labeled 37-kDa protein synthesized by nonneuronal cells. Thus, on the basis of its molecular mass, isoelectric point, amino acid composition, and immunological properties, they conclude that the 37-kDa protein is apoE. They also used light microscopic immunochemistry to localize apoE following nerve injury. They propose that apoE is synthesized by phagocytic cells in response to nerve injury for the purpose of mobilizing lipids produced as a consequence of axon degeneration

  12. Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

    Energy Technology Data Exchange (ETDEWEB)

    AlbarracIn, A L [Catedra de Neurociencias, Facultad de Medicina, Universidad Nacional de Tucuman, Av. Roca 2200, PC 4000 (Argentina); Farfan, F D [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina); Felice, C J [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina)

    2007-11-15

    In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle.

  13. Selective recovery of fascicular activity in peripheral nerves

    Science.gov (United States)

    Wodlinger, B.; Durand, D. M.

    2011-10-01

    The peripheral nerves of an amputee's residual limb still carry the information required to provide the robust, natural control signals needed to command a dexterous prosthetic limb. However, these signals are mixed in the volume conductor of the body and extracting them is an unmet challenge. A beamforming algorithm was used to leverage the spatial separation of the fascicular sources, recovering mixed pseudo-spontaneous signals with normalized mean squared error of 0.14 ± 0.10 (n = 12) in an animal model. The method was also applied to a human femoral nerve model using computer simulations and recovered all five fascicular-group signals simultaneously with R2 = 0.7 ± 0.2 at a signal-to-noise ratio of 0 dB. This technique accurately separated peripheral neural signals, potentially providing the voluntary, natural and robust command signals needed for advanced prosthetic limbs.

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

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-01-01

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

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

    Science.gov (United States)

    Wang, Yang; Li, Zheng-Wei; Luo, Min; Li, Ya-Jun; Zhang, Ke-Qiang

    2015-06-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel grafts than with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells grafts and the autologous nerve grafts. PMID:26199615

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

    Directory of Open Access Journals (Sweden)

    Olree Kenneth S

    2006-07-01

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

  17. Tumour necrosis factor ? enhances CCL2 and ICAM-1 expression in peripheral nerve microvascular endoneurial endothelial cells

    Directory of Open Access Journals (Sweden)

    Evan B. Stubbs

    2013-02-01

    Full Text Available Recruitment and trafficking of autoreactive leucocytes across the BNB (blood–nerve barrier is an early pathological insult in GBS (Guillain-Barré syndrome, an aggressive autoimmune disorder of the PNS (peripheral nervous system. Whereas the aetiology and pathogenesis of GBS remain unclear, pro-inflammatory cytokines, including TNF? (tumour necrosis factor ?, are reported to be elevated early in the course of GBS and may initiate nerve injury by activating the BNB. Previously, we reported that disrupting leucocyte trafficking in vivo therapeutically attenuates the course of an established animal model of GBS. Here, PNMECs (peripheral nerve microvascular endothelial cells that form the BNB were harvested from rat sciatic nerves, immortalized by SV40 (simian virus 40 large T antigen transduction and subsequently challenged with TNF?. Relative changes in CCL2 (chemokine ligand 2 and ICAM-1 (intercellular adhesion molecule 1 expression were determined. We report that TNF? elicits marked dose- and time-dependent increases in CCL2 and ICAM-1 mRNA and protein content and promotes secretion of functional CCL2 from immortalized and primary PNMEC cultures. TNF?-mediated secretion of CCL2 promotes, in vitro, the transendothelial migration of CCR2-expressing THP-1 monocytes. Increased CCL2 and ICAM-1 expression in response to TNF? may facilitate recruitment and trafficking of autoreactive leucocytes across the BNB in autoimmune disorders, including GBS.

  18. Nerve growth factor induces sensitivity to botulinum neurotoxin type A in norepinephrine-secreting PC12 cells.

    Science.gov (United States)

    Banerjee, A; Martin, T F; DasGupta, B R

    1993-12-24

    Inhibition of Ca(2+)-activated norepinephrine secretion by the botulinum neurotoxin (NT) serotypes A and E was examined in permeabilized PC12 cells. The dichain type E NT reduced with dithiothreitol (DTT) completely inhibited secretion whereas the dichain type A NT reduced with DTT exhibited incomplete inhibitory activity. In contrast, Ca(2+)-activated secretion in PC12 cells treated with nerve growth factor (NGF) was completely inhibited by reduced type A NT. The NGF-treated PC12 cells retained a sensitivity to the type E NT similar to that of untreated PC12 cells. These results indicate that the intracellular mechanisms of inhibition of the types E and A NTs are distinct. NGF appears to either induce the expression of a component selectively required for type A NT sensitivity, or otherwise modifies the secretory apparatus to acquire type A NT sensitivity. PMID:8152624

  19. Skin derived precursor Schwann cells improve behavioral recovery for acute and delayed nerve repair.

    Science.gov (United States)

    Khuong, Helene T; Kumar, Ranjan; Senjaya, Ferry; Grochmal, Joey; Ivanovic, Aleksandra; Shakhbazau, Antos; Forden, Joanne; Webb, Aubrey; Biernaskie, Jeffrey; Midha, Rajiv

    2014-04-01

    Previous work has shown that infusion of skin-derived precursors pre-differentiated into Schwann cells (SKP-SCs) can remyelinate injured and regenerating axons, and improve indices of axonal regeneration and electrophysiological parameters in rodents. We hypothesized that SKP-SC therapy would improve behavioral outcomes following nerve injury repair and tested this in a pre-clinical trial in 90 rats. A model of sciatic nerve injury and acellular graft repair was used to compare injected SKP-SCs to nerve-derived Schwann cells or media, and each was compared to the gold standard nerve isograft repair. In a second experiment, rats underwent right tibial nerve transection and received either acute or delayed direct nerve repair, with injections of either 1) SKP-SCs distal to the repair site, 2) carrier medium alone, or 3) dead SKP-SCs, and were followed for 4, 8 or 17weeks. For delayed repairs, both transected nerve ends were capped and repaired 11weeks later, along with injections of cells or media as above, and followed for 9 additional weeks (total of 20weeks). Rats were serially tested for skilled locomotion and a slip ratio was calculated for the horizontal ladder-rung and tapered beam tasks. Immediately after nerve injury and with chronic denervation, slip ratios were dramatically elevated. In the GRAFT repair study, the SKP-SC treated rats showed statistically significant improvement in ladder rung as compared to all other groups, and exhibited the greatest similarity to the sham controls on the tapered beam by study termination. In the ACUTE repair arm, the SKP-SC group showed marked improvement in ladder rung slip ratio as early as 5weeks after surgery, which was sustained for the duration of the experiment. Groups that received media and dead SKP-SCs improved with significantly slower progression. In the DELAYED repair arm, the SKP-SC group became significantly better than other groups 7weeks after the repair, while the media and the dead SKP-SCs showed no significant improvement in slip ratios. On histomorphometrical analysis, SKP-SC group showed significantly increased mean axon counts while the percent myelin debris was significantly lower at both 4 and 8weeks, suggesting that a less inhibitory micro-environment may have contributed to accelerated axonal regeneration. For delayed repair, mean axon counts were significantly higher in the SKP-SC group. Compound action potential amplitudes and muscle weights were also improved by cell therapy. In conclusion, SKP-SC therapy improves behavioral recovery after acute, chronic and nerve graft repair beyond the current standard of microsurgical nerve repair. PMID:24440805

  20. The efflux of choline from nerve cells: mediation by ionic gradients and functional exchange of choline from glia to neurons

    International Nuclear Information System (INIS)

    This paper analyzes the relationship between ions and the efflux of choline, and suggests the possibility of a balance effect for choline fluxes which is produced and maintained by ioinic gradients. It is also suggested that glial cells may actively exchange choline with neurons during nerve actively exchange choline with neurons during nerve activity, and that they may function as a choline reservoir for neuronal needs. The study shows that neurons and glial cells spontaneously discharge choline into the incubation medium. The exiting choline is essentially of free origin, as can be seen in an illustration provided. Neurons and glial cells had been prelabelled with (14C) choline overnight, and labelled for 15 min with tritium-choline. The higher amount of tritium-choline exiting the cells indicates that it is the freshly labelled choline which is preferentially released. The remaining of (14C) - choline exiting the cells corresponds to the free choline of phospholipid origin which amounts to about one third of the total free choline content

  1. Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

    Science.gov (United States)

    Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

    1996-01-01

    OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular rather than dual-chamber pacing may be due in part to increased sympathetic nervous outflow.

  2. Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

    Science.gov (United States)

    Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

    1996-01-01

    OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular rather than dual-chamber pacing may be due in part to increased sympathetic nervous outflow.

  3. Chicken HOXA3 Gene: Its Expression Pattern and Role in Branchial Nerve Precursor Cell Migration

    Directory of Open Access Journals (Sweden)

    Natsuko Watari-Goshima, Osamu Chisaka

    2011-01-01

    Full Text Available In vertebrates, the proximal and distal sensory ganglia of the branchial nerves are derived from neural crest cells (NCCs and placodes, respectively. We previously reported that in Hoxa3 knockout mouse embryos, NCCs and placode-derived cells of the glossopharyngeal nerve were defective in their migration. In this report, to determine the cell-type origin for this Hoxa3 knockout phenotype, we blocked the expression of the gene with antisense morpholino oligonucleotides (MO specifically in either NCCs/neural tube or placodal cells of chicken embryos. Our results showed that HOXA3 function was required for the migration of the epibranchial placode-derived cells and that HOXA3 regulated this cell migration in both NCCs/neural tube and placodal cells. We also report that the expression pattern of chicken HOXA3 was slightly different from that of mouse Hoxa3.

  4. Neurobiological Observations of Bone Mesenchymal Stem Cells in vitro and in vivo of Injured Sciatic Nerve in Rabbit

    Directory of Open Access Journals (Sweden)

    Al-Jashamy Karim

    2011-01-01

    Full Text Available The PKH26 is a fluorescent lipophilic dyes used for the study of Asymmetric cell Divisions (ASDs and efficiently purifies the stem cell fraction. The aim of this study was to explore the neurobiological characteristics in vitro and in vivo and tracking fate of the transplanted rabbit Bone Marrow-Mesenchymal Stem Cells (rBM-MSCs. A fluorescent microscope was used to determine the changes in cell size, fluorescence intensity during tissue culture, track cell divisions and the distribution of PKH26 dye between daughter cells. The results showed the identification of ASDs based on fluorescence intensity of the PKH26 dye was distributed equally between daughter cells at each division in vitro. The labeling BMSCs with PKH26 showed within the wall of the neurons in the dorsal root ganglia in vivo. Labeled BMSCs which are fibroblastic-like cells in P4 showed oval shaped and less density than P2. Direct examine of the labeled BMSCs in the cryosections at 16 weeks post operation showed the BMSCs were differentiated and appeared as like Schwann cells in an anastomosed sciatic nerve in the Local Treated Group (LTG. In the Systemic Treated Group (STG sections, the labeled BMSCs were migrated to the anastomosed sciatic nerve, ipsilateral lumber dorsal root ganglia resembling glial and stellate cells and some of the labeled cells migrated to the anterior horn of spinal cord (motor neuron. In conclusion, the biological behaviors of BMSCs in vitro and in vivo showed highly mitosis at P2, activated fibroblast-like cells, differentiated to functional myelinating Schwann-like cells in LTG. The BMSCs in STG migrated and engrafted at the dorsal root ganglia as a neuron and glial cell, glial cells and satellite in the spinal cord.

  5. [Transplanted epidermal neural crest stem cell in a peripheral nerve gap].

    Science.gov (United States)

    Zhang, Lu; Zhang, Jieyuan; Li, Bingcang; Liu, Zheng; Liu, Bin

    2014-04-01

    Neural crest stem cells originated from hair follicle (epidermal neural crest stem cell, EPI-NCSC) are easy to obtain and have potentials to differentiate into various tissues, which make them eminent seed cells for tissue engineering. EPI-NCSC is now used to repair nerve injury, especially, the spinal cord injury. To investigate their effects on repairing peripheral nerve injury, EPI-NCSC from a GFP-SD rat were primarily cultured on coated dishes and on a poly lactic acid coglycolic acid copolymer (PLGA) membrane. Methyl thiazolyl tetrazolium (MTT) assay showed that the initial adhesion rate of EPI-NCSC was 89.7% on PLGA membrane, and the relative growth rates were 89.3%, 87.6%, 85.6%, and 96.6% on the 1st, 3rd, 5th, 7th day respectively. Cell cycles and DNA ploidy analysis demonstrated that cell cycles and proliferation indexes of cultured EPI-NCSC had the same variation pattern on coated dishes and PLGA membrane. Then cultured EPI-NCSC were mixed with equal amount of extracellular matrix and injected into a PLGA conduit to connect a 10 mm surgery excision gap of rat sciatic nerve, Dulbecco's Modified Eagle's medium (DMEM) was used to substitute EPI-NCSC in the control group. After four weeks of transplantation, the defected sciatic nerve achieved a histological restoration, the sensory function of rat hind limb was partly recovered and the sciatic nerve index was also improved. The above results showed that a PLGA conduit filled with EPI-NCSC has a good repair effect on the peripheral nerve injury. PMID:25195250

  6. Bone marrow-derived, neural-like cells have the characteristics of neurons to protect the peripheral nerve in microenvironment.

    Science.gov (United States)

    Guo, Shi-Lei; Zhang, Zhi-Ying; Xu, Yan; Zhi, Yun-Xia; Han, Chang-Jie; Zhou, Yu-Hao; Liu, Fang; Lin, Hai-Yan; Zhang, Chuan-Sen

    2015-01-01

    Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that "neural-like cells" may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG), immunohistochemistry, and transmission electron microscopy (TEM) were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve. PMID:25861281

  7. Myocardial adrenergic nerve activity in valvular diseases assessed by iodine-123-metaiodobenzylguanidine myocardial scintigraphy

    International Nuclear Information System (INIS)

    Iodine-123-metaiodobenzylguanidine (MIBG) imaging was used to assess myocardial adrenergic nerve activity in patients with heart failure. MIBG planar images were obtained in 94 patients. The uptake of MIBG, calculated as the heart-to-mediastinum activity ratio in the immediate image (15 min), showed a significant decrease only in patients with severe heart failure due to cardiomyopathy, but was not changed in those with valvular diseases. Storage and release of MIBG, calculated as the percentage myocardial MIBG washout from 15 min to 4 hours after isotope injection, was substantially accelerated in both patients with cardiomyopathy and valvular diseases in proportion to the severity of heart failure. These data suggest that, in severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. Also, myocardial adrenergic nerve activity is accelerated in proportion to the severity of heart failure independent of the underlying cause. MIBG images were analyzed in 20 patients with mitral stenosis with the same methods to clarify whether myocardial adrenergic nerve activity is different in patients with heart failure without left ventricular volume or pressure overload. Myocardial uptake of MIBG did not show any significant difference. The percentage myocardial MIBG washout was increased in patients with severe heart failure. The closest correlation was between myocardial washout and cardiac output. In heart failure due to mitral stenosis, myocardial ailure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. Decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification. (author)

  8. Up-Regulation of NF45 Correlates with Schwann Cell Proliferation After Sciatic Nerve Crush.

    Science.gov (United States)

    Wang, Youhua; Zhou, Shiran; Xu, Hua; Yan, Shixian; Xu, Dawei; Zhang, Yi

    2015-05-01

    Nuclear factor (NF)45 (also known as interleukin enhancer-binding factor (ILF)2), is a transcription factor that interacts with NF90 to regulate gene expression. It has long been implicated in the regulation of cell proliferation. However, the role of NF45 in the process of peripheral nervous system regeneration after injury remains poorly understood. Herein, we investigated the spatiotemporal expression of NF45 in a rat sciatic nerve crush model. We detected the up-regulated expression of NF45 in Schwann cell after sciatic nerve crush. What's more, the expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA) exhibited a similar tendency with that of NF45. In cell cultures, we observed increased expression of NF45 during the process of TNF-?-induced Schwann cell proliferation, whereas the protein level of p21 was down-regulated. Interference of NF45 led to enhanced expression of p21 and also impaired proliferation of Schwan cells. Taken together, our data implicated that NF45 was up-regulated in the sciatic nerve after crush, which was associated with proliferation of Schwann cell. PMID:25566957

  9. Cilnidipine inhibits the sympathetic nerve activity and improves baroreflex sensitivity in patients with hypertension.

    Science.gov (United States)

    Kishi, Takuya; Hirooka, Yoshitaka; Konno, Satomi; Sunagawa, Kenji

    2009-05-01

    N-type calcium channel blocker, cilnidipine, is reported not to increase the heart rate in spite of the strong depressor effect. However, it has not been determined whether cilnidipine has the sympatho-inhibitory effects or not. Moreover, the effect of cilnidipine on the baroreflex control has not been determined. The aim of this study was to determine the effect of cilnidipine on sympathetic and parasympathetic nerve activity, and baroreflex sensitivity. We studied five hypertensive patients treated with 10 mg cilnidipine (10-mg group) and five hypertensive patients treated with 20 mg cilnidipine (20-mg group). Before the treatment and 6 months after the treatment, we measured the blood pressure, spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV), and blood pressure variability (BPV). After 6 months, systolic blood pressure (SBP) and the low-frequency component of systolic BPV expressed in normalized units (LFnuSBP), as the parameter of sympathetic nerve activity, was significantly decreased in both groups, and the suppressive effects were stronger in the 20-mg group than in the 10-mg group. The high-frequency component of HRV expressed in normalized units, as the parameter of parasympathetic nerve activity, and BRS were significantly increased in 20-mg group, but not significant in 10-mg group. These results suggest that 6 months treatment with cilnidipine for hypertension has the sympatho-inhibtory effect, and that high-dose cilnidipine improves the parasympathetic nerve activity and baroreflex control in patients with hypertension. PMID:19387900

  10. Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair Respostas astrocitárias na medula espinal do rato submetido ao esmagamento duplo do nervo ciático e tratado com injeção local de suspensão de células de Schwann cultivadas ou de extrato de medula espinal lesada: implicações na terapia celular para o reparo do nervo

    OpenAIRE

    João Gabriel Martins Dallo; Bernardo Vergara Reichert; José Benedito Ramos Valladão Júnior; Camila Silva; Bianca Aparecida de Luca; Beatriz de Freitas Azevedo Levy; Gerson Chadi

    2007-01-01

    PURPOSE: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fiber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or...

  11. Distribution of Mesenchymal Stem Cells and Effects on Neuronal Survival and Axon Regeneration after Optic Nerve Crush and Cell Therapy

    Science.gov (United States)

    Mesentier-Louro, Louise Alessandra; Zaverucha-do-Valle, Camila; da Silva-Junior, Almir Jordão; Nascimento-dos-Santos, Gabriel; Gubert, Fernanda; de Figueirêdo, Ana Beatriz Padilha; Torres, Ana Luiza; Paredes, Bruno D.; Teixeira, Camila; Tovar-Moll, Fernanda; Mendez-Otero, Rosalia; Santiago, Marcelo F.

    2014-01-01

    Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC) injected into the vitreous body in a model of optic nerve injury. Adult (3–5 months old) Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1? expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime. PMID:25347773

  12. Delayed Nerve Stimulation Promotes Axon-Protective Neurofilament Phosphorylation, Accelerates Immune Cell Clearance and Enhances Remyelination In Vivo in Focally Demyelinated Nerves

    Science.gov (United States)

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

    2014-01-01

    Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination) on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP) and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF) in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies. PMID:25310564

  13. Hirschsprungs disease: Is there a relationship between mast cells and nerve fibers?

    Directory of Open Access Journals (Sweden)

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

    2009-03-01

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

  14. Leptin-Induced Sympathetic Nerve Activation: Signaling Mechanisms and Cardiovascular Consequences in Obesity

    OpenAIRE

    Rahmouni, Kamal

    2010-01-01

    Obesity increases cardiovascular morbidity and mortality in part by inducing hypertension. One factor linking excess fat mass to cardiovascular diseases may be the sympathetic cardiovascular actions of leptin. Initial studies of leptin showed it regulates appetite and enhances energy expenditure by activating sympathetic nerve activity (SNA) to thermogenic brown adipose tissue. Further study, however, demonstrated leptin also causes sympathetic excitation to the kidney that, in turn, increase...

  15. Whole body heat stress attenuates baroreflex control of muscle sympathetic nerve activity during postexercise muscle ischemia

    OpenAIRE

    Cui, Jian; Shibasaki, Manabu; Davis, Scott L.; Low, David A.; Keller, David M.; Crandall, Craig G.

    2009-01-01

    Both whole body heat stress and stimulation of muscle metabolic receptors activate muscle sympathetic nerve activity (MSNA) through nonbaroreflex pathways. In addition to stimulating muscle metaboreceptors, exercise has the potential to increase internal temperature. Although we and others report that passive whole body heating does not alter the gain of the arterial baroreflex, it is unknown whether increased body temperature, often accompanying exercise, affects baroreflex function when mus...

  16. Inhibition of cardiac sympathetic nerve activity during intravenous administration of lidocaine.

    OpenAIRE

    Miller, B. D.; Thames, M. D.; Mark, A. L.

    1983-01-01

    The antiarrhythmic action of lidocaine has been attributed solely to its direct electrophysiological effects on the heart. However, lidocaine is particularly effective in treating ventricular arrhythmias associated with increased sympathetic activity, e.g., in myocardial infarction and digitalis toxicity. We tested the hypothesis that lidocaine administered intravenously depressed cardiac sympathetic nerve activity (CSNA). We measured CSNA in six dogs in control state and after lidocaine in d...

  17. Schwann cell behavior after nerve repair by means of tissue-engineered muscle-vein combined guides

    OpenAIRE

    ROBECCHI, Mariagiuseppina; Perroteau, Isabelle; Raimondo, Stefania; Geuna, Stefano; Tos, Pierluigi

    2005-01-01

    Schwann cells play a critical role in peripheral nerve regeneration. When a non-nervous conduit is used to bridge a nerve defect, the conduit is soon colonized by a number of Schwann cells that make a pathway for regrowing axons. By using electron microscopy, immunohistochemistry, and reverse transcriptase-polymerase chain reaction analysis, we have investigated the behavior of migratory glial cells along a particular type of autologous tissue-engineered conduit made of a vein filled with fre...

  18. Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin.

    Science.gov (United States)

    Wang, L; Hilliges, M; Jernberg, T; Wiegleb-Edström, D; Johansson, O

    1990-07-01

    Sections of human skin were processed according to the indirect immunofluorescence technique with a rabbit antiserum against human protein gene product 9.5 (PGP 9.5). Immunoreactivity was detected in intraepidermal and dermal nerve fibres and cells. The intraepidermal nerves were varicose or smooth with different diameters, running as single processes or branched, straight or bent, projecting in various directions and terminating in the stratum basale, spinosum or granulosum. The density of the intraepidermal nerves varied between the different skin areas investigated. PGP 9.5-containing axons of the lower dermis were found in large bundles. They separated into smaller axon bundles within the upper dermis, entering this portion of the skin perpendicular to the surface. Then they branched into fibres mainly arranged parallel to the epidermal-dermal junctional zone. However, the fibres en route to the epidermis traversed the upper dermis more or less perpendicularly. Furthermore, immunoreactive dermal nerve fibres were found in the Meissner corpuscles, the arrector pili muscles, hair follicles, around the eccrine and apocrine sweat glands and around certain blood vessels. Such fibres were also observed around most subcutaneous blood vessels, sometimes heavily innervating these structures. Numerous weakly-to-strongly PGP 9.5-immunoreactive cells were found both in the epidermis and in the dermis. PMID:2143435

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

    Directory of Open Access Journals (Sweden)

    Decosterd Isabelle

    2009-09-01

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

  20. Monitoring of immune cell response to B cell depletion therapy and nerve root injury using SPIO enhanced MRI

    Science.gov (United States)

    Thorek, Daniel L.

    2009-12-01

    Magnetic resonance (MR) is a robust platform for non-invasive, high-resolution anatomical imaging. However, MR imaging lacks the requisite sensitivity and contrast for imaging at the cellular level. This represents a clinical impediment to greater diagnostic accuracy. Recent advances have allowed for the in vivo visualization of populations and even of individual cells using superparamagnetic iron oxide (SPIO) MR contrast agents. These nanoparticles, commonly manifested as a core of a single iron oxide crystal or cluster of crystals coated in a biocompatible shell, function to shorten proton relaxation times. In MR imaging these constructs locally dephase protons, resulting in a decrease in signal (hypointensity) localized to the region of accumulation of SPIO. In the context of immune cell imaging, SPIO can provide insight into the cellular migration patterns, trafficking, temporal dynamics and progression of diseases and their related pathological states. Furthermore, by visualizing the presence and activity of immune cells, SPIO-enabled cellular imaging can help evaluate the efficacy of therapy in immune disorders. This thesis examines the production, modification and application of SPIO in a range of in vitro and in vivo immune-response-relevant cellular systems. The role of different nanoparticle characteristics including diameter, surface charge and concentration are investigated in the labeling of T cells in culture. Following optimization of SPIO loading conditions for lymphocytes, the effect these particles have on the activation of primary B cells are elucidated. B cells are tracked using a variety of modalities, with and without the application of B cell depleting therapy. This is to evaluate the efficacy of SPIO as in vivo marker for B cell distribution. Unmodified SPIO were applied to monitor macrophage infiltration in a transient nerve root compression model, with implications for neck pain diagnosis and treatment. Nanoparticle accumulation and MR hypointensity was correlated to the presence of activated macrophage at the site of injury. Taken together, the application of SPIO to study nanoparticle uptake in vitro and visualization of immune cells in vivo provide a basis for advanced study and diagnosis of diverse pathologies.

  1. Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction?

    Directory of Open Access Journals (Sweden)

    Christine Radtke

    2012-10-01

    Full Text Available Successful nerve regeneration after nerve trauma is not only important for the restoration of motor and sensory functions, but also to reduce the potential for abnormal sensory impulse generation that can occur following neuroma formation. Satisfying functional results after severe lesions are difficult to achieve and the development of interventional methods to achieve optimal functional recovery after peripheral nerve injury is of increasing clinical interest. Olfactory ensheathing cells (OECs have been used to improve axonal regeneration and functional outcome in a number of studies in spinal cord injury models. The rationale is that the OECs may provide trophic support and a permissive environment for axonal regeneration. The experimental transplantation of OECs to support and enhance peripheral nerve regeneration is much more limited. This chapter reviews studies using OECs as an experimental cell therapy to improve peripheral nerve regeneration.

  2. Imaging stretch-activated firing of spinal afferent nerve endings in mouse colon

    OpenAIRE

    Travis, Lee; Spencer, Nick J

    2013-01-01

    Spinal afferent neurons play a major role in detecting noxious and innocuous stimuli from visceral organs, such as the gastrointestinal tract. However, all our understanding about spinal afferents has been obtained from recordings of spinal afferent axons, or cell bodies that lie outside the gut wall, or peripheral organ they innervate. No recordings have been made directly from spinal afferent nerve endings, which is where sensory transduction occurs. We developed a preparation whereby recor...

  3. Engraftment and Differentiation of Embryonic Stem Cell–Derived Neural Progenitor Cells in the Cochlear Nerve Trunk: Growth of Processes into the Organ of Corti

    OpenAIRE

    Corrales, C. Eduardo; Pan, Luying; Li, Huawei; Liberman, M. Charles; Heller, Stefan; Edge, Albert S. B.

    2006-01-01

    Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. To determine whether we could replace neurons lost to primary neuronal degeneration, we injected EYFP-expressing embryonic stem cell–derived mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed animals 1 week after destroying the cochlear nerve (spiral ganglion) cells while leaving hair cells intact by ouabain application to the round window at the base of the cochle...

  4. Tetrahydrobiopterin lowers muscle sympathetic nerve activity and improves augmentation index in patients with chronic kidney disease.

    Science.gov (United States)

    Park, Jeanie; Liao, Peizhou; Sher, Salman; Lyles, Robert H; Deveaux, Don D; Quyyumi, Arshed A

    2015-02-01

    Chronic kidney disease (CKD) is characterized by overactivation of the sympathetic nervous system (SNS) that contributes to cardiovascular risk. Decreased nitric oxide (NO) bioavailability is a major factor contributing to SNS overactivity in CKD, since reduced neuronal NO leads to increased central SNS activity. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase that increases NO bioavailability in experimental models of CKD. We conducted a randomized, double-blinded, placebo-controlled trial testing the benefits of oral sapropterin dihydrochloride (6R-BH4, a synthetic form of BH4) in CKD. 36 patients with CKD and hypertension were randomized to 12 wk of 1) 200 mg 6R-BH4 twice daily + 1 mg folic acid once daily; vs. 2) placebo + folic acid. The primary endpoint was a change in resting muscle sympathetic nerve activity (MSNA). Secondary endpoints included arterial stiffness using pulse wave velocity (PWV) and augmentation index (AIx), endothelial function using brachial artery flow-mediated dilation and endothelial progenitor cells, endothelium-independent vasodilatation (EID), microalbuminuria, and blood pressure. We observed a significant reduction in MSNA after 12 wk of 6R-BH4 (-7.5 ± 2.1 bursts/min vs. +3.2 ± 1.3 bursts/min; P = 0.003). We also observed a significant improvement in AIx (by -5.8 ± 2.0% vs. +1.8 ± 1.7 in the placebo group, P = 0.007). EID increased significantly (by +2.0 ± 0.59%; P = 0.004) in the 6R-BH4 group, but there was no change in endothelial function. There was a trend toward a reduction in diastolic blood pressure by -4 ± 3 mmHg at 12 wk with 6R-BH4 (P = 0.055). 6R-BH4 treatment may have beneficial effects on SNS activity and central pulse wave reflections in hypertensive patients with CKD. PMID:25477424

  5. Respiratory activity in glossopharyngeal, vagus and accessory nerves and pharyngeal constrictors in newborn rat in vitro.

    Science.gov (United States)

    Iizuka, M

    2001-04-15

    1. Previously, in a brainstem-spinal cord-rib preparation from neonatal rats we demonstrated that a decrement in extracellular pH (from about 7.4 to 7.1) caused expiratory activity in an internal intercostal muscle (IIM) during the first half of the expiratory phase (Ea). As the initial step in finding nerves or muscles firing during the second half of the expiratory phase (Eb), the patterns of activity in the glossopharyngeal, vagus and accessory nerves were examined in the present study. 2. Since the emerging motor rootlets of these three nerves (> 20; collected into about 10 bundles before the jugular foramen) are distributed in a continuous fashion from rostral to caudal levels of the brainstem, visual identification was impossible. Therefore, antidromic compound action potentials evoked by stimulation of the glossopharyngeal nerve (IX), the pharyngeal branch of the vagus nerve (PhX), the superior laryngeal nerve (SLN), the cervical vagus nerve (CX) and the accessory nerve (XI) were recorded from the peripheral stumps of the various rootlets. Nerve rootlets could be categorised into rostral, intermediate and caudal groups (rostIX-XI, intIX-XI, caudIX-XI). The rostIX-XI rootlets showed their largest potential on IX stimulation, while the intIX-XI and caudIX-XI rootlets showed their largest potentials on CX stimulation. The intIX-XI rootlets showed larger potentials on PhX and SLN stimulation than the caudIX-XI rootlets. 3. Activity was recorded simultaneously from the central stumps of the rootlets in the above three groups. Most rootlets showed inspiratory bursts. Under low pH conditions, all representatives of group rostIX-XI, most of intIX-XI and about half of caudIX-XI showed additional bursts during the Ea phase. Groups intIX-XI and caudIX-XI but not rostIX-XI also showed discrete bursts during the Eb phase in some preparations. In general, expiratory activity was prominent in intIX-XI. The spinal branch of XI showed no consistent respiratory activity. 4. Since the intIX-XI rootlets showed Eb bursts and large antidromic potentials on stimulation of PhX and SLN (which innervate the inferior pharyngeal constrictor muscle (IPC)), electromyograms were recorded from the rostral and caudal parts of IPC (rIPC and cIPC). Under low pH conditions, cIPC showed bursts during the Ea and Eb phases, while rIPC showed bursts predominantly during the Eb phase. 5. These results indicate that recording from rIPC would be a useful way of examining the neuronal mechanisms responsible for Eb phase activity. PMID:11306670

  6. Wide distribution of immunoreactive renin in nerve cells of human brain.

    OpenAIRE

    Slater, E. E.; Defendini, R.; Zimmerman, E. A.

    1980-01-01

    By use of the indirect peroxidase-antiperoxidase complex immunocytochemical technique, antibody to purified human renal renin was applied to formalin-fixed paraffin sections of human cadaver brain. Immune reaction products were observed in most nerve cells in all areas of the brain examined; staining was limited to the soma and proximal dendrites. These experiments have confirmed the presence of a renin-like substance in central nervous tissue and suggest a more generalized function for "brai...

  7. Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve regeneration in an axonotmesis rat model

    OpenAIRE

    Fregnan, Federica; Geuna, Stefano; Raimondo, Stefania; Fornaro, Michele; Gambarotta, Giovanna

    2008-01-01

    Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test hybrid chitosan membranes to use in peripheral nerve reconstruction, either alone or enriched with N1E-115 neural cells. Hybrid chitosan membranes were tested in vitro, to assess their ability in supporting N1E-115 cell survival and differentiation, and in vivo to assess biocompatibility as well as to evaluate their effects on nerve f...

  8. Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity

    OpenAIRE

    Holbein, Walter W.; Toney, Glenn M.

    2013-01-01

    Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P < 0.01), analysis of respiratory rhythmic bursting of sSNA reveale...

  9. Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans

    OpenAIRE

    Fairfax, Seth T.; Padilla, Jaume; Vianna, Lauro C.; Davis, Michael J.; Fadel, Paul J.

    2013-01-01

    Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single...

  10. Skin sympathetic nerve activity in humans during exposure to emotionally-charged images: sex differences

    OpenAIRE

    Brown, Rachael; Macefield, Vaughan G.

    2014-01-01

    While it is known that anxiety or emotional arousal affects skin sympathetic nerve activity (SSNA), the galvanic skin response (GSR) is the most widely used parameter to infer increases in SSNA during stress or emotional studies. We recently showed that SSNA provides a more sensitive measure of emotional state than effector-organ responses. The aim of the present study was to assess whether there are gender differences in the responses of SSNA and other physiological parameters such as blood ...

  11. Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration

    OpenAIRE

    Wilhelm, Jennifer C.; Xu, Mei; Cucoranu, Delia; Chmielewski, Sarah; Holmes, Tiffany; Lau, Kelly; Bassell, Gary J.; English, Arthur W.

    2012-01-01

    After peripheral nerve injury, neurotrophins play a key role in the regeneration of damaged axons which can be augmented by exercise, although the distinct roles played by neurons and Schwann cells are unclear. In this study, we evaluated the requirement for the neurotrophin, brain derived neurotrophic factor (BDNF), in neurons and Schwann cells, for the regeneration of peripheral axons after injury. Common fibular or tibial nerves in thy-1-YFP-H mice were cut bilaterally and repaired using a...

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

    Directory of Open Access Journals (Sweden)

    João G Franca

    2014-10-01

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

  13. Enhancement of median nerve regeneration by mesenchymal stem cells engraftment in an absorbable conduit: improvement of peripheral nerve morphology with enlargement of somatosensory cortical representation

    Science.gov (United States)

    Oliveira, Julia T.; Bittencourt-Navarrete, Ruben Ernesto; de Almeida, Fernanda M.; Tonda-Turo, Chiara; Martinez, Ana Maria B.; Franca, João G.

    2014-01-01

    We studied the morphology and the cortical representation of the median nerve (MN), 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL) conduit with or without bone marrow-derived mesenchymal stem cell (MSC) transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1), electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in three groups: MN Intact (n = 4), PCL-Only (n = 3), and PCL+MSC (n = 3). Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group) or without (PCL-Only group) injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to five animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383 ± 390 fibers; 2.3 mm2, respectively) than the PCL-Only group (2,226 ± 575 fibers; 1.6 mm2). In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN. PMID:25360086

  14. Excitatory and inhibitory effects of prolactin release activated by nerve stimulation in rat anterior pituitary

    Directory of Open Access Journals (Sweden)

    Gao Li-Zhi

    2009-12-01

    Full Text Available Abstract Background A series of studies showed the presence of substantial amount of nerve fibers and their close relationship with the anterior pituitary gland cells. Our previous studies have suggested that aside from the classical theory of humoral regulation, the rat anterior pituitary has direct neural regulation on adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses are found on every type of the hormone-secreting cells, many on lactotrophs. The present study was aimed at investigating the physiological significance of this synaptic relationship on prolactin release. Methods The anterior pituitary of rat was sliced and stimulated with electrical field in a self-designed perfusion chamber. The perfusate was continuously collected in aliquots and measured by radioimmunoassay for prolactin levels. After statistic analysis, differences of prolactin concentrations within and between groups were outlined. Results The results showed that stimulation at frequency of 2 Hz caused a quick enhancement of prolactin release, when stimulated at 10 Hz, prolactin release was found to be inhibited which came slower and lasted longer. The effect of nerve stimulation on prolactin release is diphasic and frequency dependent. Conclusions The present in vitro study offers the first physiological evidence that stimulation of nerve fibers can affect prolactin release in rat anterior pituitary. Low frequency stimulation enhances prolactin release and high frequency mainly inhibits it.

  15. Modelling the vascular response to sympathetic postganglionic nerve activity.

    Science.gov (United States)

    Briant, Linford J B; Paton, Julian F R; Pickering, Anthony E; Champneys, Alan R

    2015-04-21

    This paper explores the influence of burst properties of the sympathetic nervous system on arterial contractility. Specifically, a mathematical model is constructed of the pathway from action potential generation in a sympathetic postganglionic neurone to contraction of an arterial smooth muscle cell. The differential equation model is a synthesis of models of the individual physiological processes, and is shown to be consistent with physiological data. The model is found to be unresponsive to tonic (regular) stimulation at typical frequencies recorded in sympathetic efferents. However, when stimulated at the same average frequency, but with repetitive respiratory-modulated burst patterns, it produces marked contractions. Moreover, the contractile force produced is found to be highly dependent on the number of spikes in each burst. In particular, when the model is driven by preganglionic spike trains recorded from wild-type and spontaneously hypertensive rats (which have increased spiking during each burst) the contractile force was found to be 10-fold greater in the hypertensive case. An explanation is provided in terms of the summative increased release of noradrenaline. Furthermore, the results suggest the marked effect that hypertensive spike trains had on smooth muscle cell tone can provide a significant contribution to the pathology of hypertension. PMID:25698230

  16. Assessment of regional sympathetic nerve activity in vasospastic angina: analysis of iodine 123-labeled metaiodobenzylguanidine scintigraphy.

    Science.gov (United States)

    Sakata, K; Miura, F; Sugino, H; Saegusa, T; Shirotani, M; Yoshida, H; Hoshino, T; Kurata, C

    1997-04-01

    With the use of iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy, this study evaluated regional sympathetic nerve activity in vasospastic angina. Twenty male patients with left anterior descending coronary artery spasm and 18 male patients with normal coronary arteries as a control group were studied. All patients underwent quantitative 123I-MIBG scintigraphy and atropine stress 123I-MIBG scintigraphy. Both groups showed a similar heterogeneous 123I-MIBG uptake in the left ventricle. However, the regional washout rate in patients with coronary artery spasm was significantly reduced in all three territories compared with that in the control group. In vasospastic angina, the regional washout rate in the left anterior descending coronary artery territory was significantly reduced as compared with the other two regions. After intravenous injection of 1 mg atropine, the regional washout rate in the three regions significantly increased in both groups, but the regional differences between the two groups disappeared. The current study demonstrated that cardiac sympathetic nerve activity in vasospastic angina was suppressed, especially in the territory of the spasm-induced coronary artery, probably because of the enhanced parasympathetic nerve activity. PMID:9124179

  17. After-effects of exercise on haemodynamics and muscle sympathetic nerve activity in young patients with dilated cardiomyopathy.

    OpenAIRE

    Hara, K.; Floras, J. S.

    1996-01-01

    OBJECTIVE: To determine the after-effects on sympathetic nerve activity and calf and systemic haemodynamics of symptom-limited exercise in young patients with dilated cardiomyopathy. PATIENTS: 14 young patients with dilated cardiomyopathy (mean (SEM) age 35 (2) yr) and 17 healthy controls (age 29 (2) yr). METHODS: Blood pressure, muscle sympathetic nerve activity, calf blood flow, plasma noradrenaline, and stroke volume were recorded during baseline rest and an hour after symptom-limited trea...

  18. Surgical treatment options and management strategies of metastatic renal cell carcinoma to the lumbar spinal nerve roots.

    Science.gov (United States)

    Strong, Christian; Yanamadala, Vijay; Khanna, Arjun; Walcott, Brian P; Nahed, Brian V; Borges, Lawrence F; Coumans, Jean-Valery C E

    2013-11-01

    Spinal nerve root metastasis of renal cell carcinoma is a rare occurrence. In addition to treatment of the primary lesion, surgical resection of the nerve root metastasis, occasionally with sacrifice of the involved nerve, is the accepted standard of treatment. Resection often resolves presenting motor and pain symptoms due to relief of neural compression. We describe two patients with nerve root metastasis of renal cell carcinoma and their management. While locally advanced and metastatic renal cell carcinoma has been shown to be chemo- and radio-resistant, immunotherapy is a promising treatment. Given the high prevalence of systemic disease in patients with intradural metastases, systemic (and possibly intracranial) imaging can be used to identify other potential areas of disease. PMID:23931936

  19. Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury.

    Science.gov (United States)

    Song, Xian-Min; Xu, Xiao-Hui; Zhu, Jiao; Guo, Zhili; Li, Jian; He, Cheng; Burnstock, Geoffrey; Yuan, Hongbin; Xiang, Zhenghua

    2015-06-01

    Peripheral nerve injury (PNI) is a common disease, which results in a partial or total loss of motor, sensory and autonomic functions, leading to a decrease in quality of life. Schwann cells play a vital role in maintaining the peripheral nervous system and in injury and repair. Using immunohistochemistry, Western blot, calcium assay and bromodeoxyuridine (BrdU) proliferation assay, the present study clearly demonstrated that P2X7 receptors (R) were expressed in myelinating and non-myelinating Schwann cells in longitudinal sections of sciatic nerves. After sciatic nerve injury (SNI), P2X7R expression in Schwann cells of injured sciatic nerves was significantly up-regulated during the early days of SNI. Double immunofluorescence of proliferating cell nuclear antigen (PCNA) and P2X7R implied that P2X7R may be involved in proliferation of Schwann cells. Further experiments on primary cultures of Schwann cells showed that P2X7R are functionally expressed in Schwann cells of rat sciatic nerves; ATP via P2X7R can promote Schwann cell proliferation, possibly via the MAPK/ERK intracellular signalling pathway. Other possible roles of P2X7R on Schwann cells are discussed. PMID:25682129

  20. MR imaging and T2 measurements in peripheral nerve repair with activation of Toll-like receptor 4 of neurotmesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiang; Zhang, Fang; Lu, Liejing; Li, Haojiang; Wen, Xuehua; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China)

    2014-05-15

    To investigate the role of MR imaging in neurotmesis combined with surgical repair and Toll-like receptor 4 (TLR4) activation. Forty-eight rats received subepineurial microinjection of the TLR4 agonist lipopolysaccharide (LPS, n = 24) or phosphate buffered saline (PBS, n = 24) immediately after surgical repair of the transected sciatic nerve. Sequential fat-suppressed T2-weighted imaging and quantitative T2 measurements were obtained at 3, 7, 14 and 21 days after surgery, with histologic assessments performed at regular intervals. T2 relaxation times and histological quantification of the distal stumps were measured and compared. The distal stumps of transected nerves treated with LPS or PBS both showed persistent enlargement and hyperintense signal. T2 values of the distal stumps showed a rapid rise to peak level followed by a rapid decline pattern in nerves treated with LPS, while exhibiting a slow rise to peak value followed by a slow decline in nerves treated with PBS. Nerves treated with LPS exhibited more prominent macrophage recruitment, faster myelin debris clearance and more pronounced nerve regeneration. Nerves treated with TLR4 activation had a characteristic pattern of T2 value change over time. Longitudinal T2 measurements can be used to detect the enhanced repair effect associated with TLR4 activation in the surgical repair of neurotmesis. (orig.)

  1. MR imaging and T2 measurements in peripheral nerve repair with activation of Toll-like receptor 4 of neurotmesis

    International Nuclear Information System (INIS)

    To investigate the role of MR imaging in neurotmesis combined with surgical repair and Toll-like receptor 4 (TLR4) activation. Forty-eight rats received subepineurial microinjection of the TLR4 agonist lipopolysaccharide (LPS, n = 24) or phosphate buffered saline (PBS, n = 24) immediately after surgical repair of the transected sciatic nerve. Sequential fat-suppressed T2-weighted imaging and quantitative T2 measurements were obtained at 3, 7, 14 and 21 days after surgery, with histologic assessments performed at regular intervals. T2 relaxation times and histological quantification of the distal stumps were measured and compared. The distal stumps of transected nerves treated with LPS or PBS both showed persistent enlargement and hyperintense signal. T2 values of the distal stumps showed a rapid rise to peak level followed by a rapid decline pattern in nerves treated with LPS, while exhibiting a slow rise to peak value followed by a slow decline in nerves treated with PBS. Nerves treated with LPS exhibited more prominent macrophage recruitment, faster myelin debris clearance and more pronounced nerve regeneration. Nerves treated with TLR4 activation had a characteristic pattern of T2 value change over time. Longitudinal T2 measurements can be used to detect the enhanced repair effect associated with TLR4 activation in the surgical repair of neurotmesis. (orig.)

  2. Minocycline is cytoprotective in human trabecular meshwork cells and optic nerve head astrocytes by increasing expression of XIAP, survivin, and Bcl-2

    OpenAIRE

    Marcus Kernt; Neubauer, Aljoscha S.; Kirsten H Eibl; et al.

    2010-01-01

    Marcus Kernt, Aljoscha S Neubauer, Kirsten H Eibl, Armin Wolf, Michael W Ulbig, Anselm Kampik, Cristoph HirneissDepartment of Ophthalmology, Ludwig-Maximilians-University, Munich, GermanyIntroduction: Primary open-angle glaucoma (POAG) is one of the leading causes of blindness. Activation of optic nerve head astrocytes (ONHA) and loss of trabecular meshwork cells (TMC) are pathognomonic for this neurodegenerative disease. Oxidative stress and elevated levels of transforming growth factor beta...

  3. Davis-1961 revisited. Signal transmission in the cochlear hair cell-nerve junction.

    Science.gov (United States)

    Tonndorf, J

    1975-09-01

    In 1961, Hallowell Davis proposed the occurrence of the following general sequence of interrelated events in sense organs, in response to specific sensory inputs: (1) the generation of receptor potentials in the sensory cells; (2) chemical transmission across the synapses between hair cells and afferent dendrites; and (3) the triggering of postsynaptic generator potentials capable of eliciting the actual nerve action potentials. Although at the time of his writing there was no evidence for this hypothesis in the auditory organ, there is now good support for the occurrence of all three events and for their general importance in the sensory transduction process. PMID:169771

  4. Polyphosphoester microspheres for sustained release of biologically active nerve growth factor.

    Science.gov (United States)

    Xu, Xiaoyun; Yu, Hanry; Gao, Shujun; Ma, Hai-Quan; Leong, Kam W; Wang, Shu

    2002-09-01

    Controlled delivery of neurotrophic proteins to a target tissue by biodegradable polymer microspheres has been explored widely for its potential applications in the treatment of various disorders in the nervous system. We investigated in this study the potential of polyphosphoester microspheres as carriers for the sustained release of nerve growth factor (NGF), a water-soluble neurotrophic protein. Two polyphosphoesters (PPEs), P(BHET-EOP/TC) and P(DAPG-EOP), as well as poly(lactide/glycolic acid) (PLGA), were used to fabricate microspheres by a W/O/W emulsion and solvent evaporation/extraction method. With bovine serum albumin as a model protein to optimize processing parameters. P(DAPG-EOP) microspheres exhibited a lower burst effect but similar protein entrapment levels and efficiencies when compared with those made of PLGA. Bioactive NGF could be released for at least 10 weeks from the P(DAPG-EOP) microspheres, as confirmed by a neurite outgrowth assay of the PC12 cells. These NGF containing microspheres were incorporated into the nerve guide conduits that were implanted to bridge a 10 mm gap in a rat sciatic nerve model. Two weeks after implantation, immunostaining with an antibody against the neurofilament protein confirmed the presence of axons at the distal end of regenerated cables within the NGF microsphere-loaded conduits. These results demonstrated the feasibility of using biodegradable PPEs for microencapsulation of NGF and provided a basis for future therapeutic application of the microspheres. PMID:12109702

  5. Effect of SIRT1 regulating cholesterol synthesis in repairing retinal ganglion cells after optic nerve injury in rats

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2014-10-01

    Full Text Available AIM: To investigate the repair mechanism associated with cholesterol synthesis regulated by silent information regulator 1(SIRT1in rat model of optic nerve damage. METHODS: Preparation of optic nerve damage in 70 rats was randomly divided into normal group(10 rats, resveratrol treatment group(experimental group 30 ratsand PBS buffer control group(30 rats. The experimental group and control group was further divided into 3 subgroups(each group 10 rats, respectively. After 7, 14, 21d injected resveratrol or PBS, optic nerve injury were observed, then the rats were sacrificed. Retina was segregated; the surviving retinal ganglion cell(RGCswas counted. Dissection of optic nerve, cholesterol content of them were tested; RT-PCR was used to detect mRNA expression of SIRT1, SREBP2 and HMGCR; Western blot assay was used to test the protein expression levels of SIRT1, cholesterol regulatory element binding protein 2(SREBP2and HMGCR. RESULTS: The numbers of RGCs and cholesterol levels of rat model with optic nerve injury decreased significantly(PPPPCONCLUSION: Up-regulating the expression of SIRT1, SREBP2 and down-regulating HMGCR by resveratrol could repair the injury of optic nerve through promoting the synthesis of cholesterol in neurons and retinal ganglion cells in the repair process. SIRT1 may be as a promising new target for treatment on optic nerve damage.

  6. SIRT1 Activating Compounds Reduce Oxidative Stress and Prevent Cell Death in Neuronal Cells

    OpenAIRE

    KennethSShindler; LingZuo; MiraMSachdeva

    2012-01-01

    Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators re...

  7. SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells

    OpenAIRE

    Khan, Reas S.; Fonseca-Kelly, Zoe; Callinan, Catherine; Zuo, Ling; Sachdeva, Mira M.; Kenneth S. Shindler

    2012-01-01

    Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators red...

  8. Photostimulation of channelrhodopsin-2 expressing ventrolateral medullary neurons increases sympathetic nerve activity and blood pressure in rats.

    Science.gov (United States)

    Abbott, Stephen B G; Stornetta, Ruth L; Socolovsky, Carmela S; West, Gavin H; Guyenet, Patrice G

    2009-12-01

    To explore the specific contribution of the C1 neurons to blood pressure (BP) control, we used an optogenetic approach to activate these cells in vivo. A lentivirus that expresses channelrhodopsin-2 (ChR2) under the control of the catecholaminergic neuron-preferring promoter PRSx8 was introduced into the rostral ventrolateral medulla (RVLM). After 2-3 weeks, ChR2 was largely confined to Phox2b-expressing neurons (89%). The ChR2-expressing neurons were non-GABAergic, non-glycinergic and predominantly catecholaminergic (54%). Photostimulation of ChR2-transfected RVLM neurons (473 nm, 20 Hz, 10 ms, 9 mW) increased BP (15 mmHg) and sympathetic nerve discharge (SND; 64%). Light pulses at 0.2-0.5 Hz evoked a large sympathetic nerve response (16 x baseline) followed by a silent period (1-2 s) during which another stimulus evoked a reduced response. Photostimulation activated most (75%) RVLM baroinhibited neurons sampled with 1/1 action potential entrainment to the light pulses and without accommodation during 20 Hz trains. RVLM neurons unaffected by either CO(2) or BP were light-insensitive. Bötzinger respiratory neurons were activated but their action potentials were not synchronized to the light pulses. Juxtacellular labelling of recorded neurons revealed that, of these three cell types, only the cardiovascular neurons expressed the transgene. In conclusion, ChR2 expression had no discernable effect on the putative vasomotor neurons at rest and was high enough to allow precise temporal control of their action potentials with light pulses. Photostimulation of RVLM neurons caused a sizable sympathoactivation and rise in blood pressure. These results provide the most direct evidence yet that the C1 neurons have a sympathoexcitatory function. PMID:19822543

  9. Selective neural activation in a histologically derived model of peripheral nerve

    Science.gov (United States)

    Butson, Christopher R.; Miller, Ian O.; Normann, Richard A.; Clark, Gregory A.

    2011-06-01

    Functional electrical stimulation (FES) is a general term for therapeutic methods that use electrical stimulation to aid or replace lost ability. For FES systems that communicate with the nervous system, one critical component is the electrode interface through which the machine-body information transfer must occur. In this paper, we examine the influence of inhomogeneous tissue conductivities and positions of nodes of Ranvier on activation of myelinated axons for neuromuscular control as a function of electrode configuration. To evaluate these effects, we developed a high-resolution bioelectric model of a fascicle from a stained cross-section of cat sciatic nerve. The model was constructed by digitizing a fixed specimen of peripheral nerve, extruding the image along the axis of the nerve, and assigning each anatomical component to one of several different tissue types. Electrodes were represented by current sources in monopolar, transverse bipolar, and longitudinal bipolar configurations; neural activation was determined using coupled field-neuron simulations with myelinated axon cable models. We found that the use of an isotropic tissue medium overestimated neural activation thresholds compared with the use of physiologically based, inhomogeneous tissue medium, even after controlling for mean impedance levels. Additionally, the positions of the cathodic sources relative to the nodes of Ranvier had substantial effects on activation, and these effects were modulated by the electrode configuration. Our results indicate that physiologically based tissue properties cause considerable variability in the neural response, and the inclusion of these properties is an important component in accurately predicting activation. The results are used to suggest new electrode designs to enable selective stimulation of small diameter fibers.

  10. Painful nerve injury increases plasma membrane Ca2+-ATPase activity in axotomized sensory neurons

    Directory of Open Access Journals (Sweden)

    Gemes Geza

    2012-06-01

    Full Text Available Abstract Background The plasma membrane Ca2+-ATPase (PMCA is the principal means by which sensory neurons expel Ca2+ and thereby regulate the concentration of cytoplasmic Ca2+ and the processes controlled by this critical second messenger. We have previously found that painful nerve injury decreases resting cytoplasmic Ca2+ levels and activity-induced cytoplasmic Ca2+ accumulation in axotomized sensory neurons. Here we examine the contribution of PMCA after nerve injury in a rat model of neuropathic pain. Results PMCA function was isolated in dissociated sensory neurons by blocking intracellular Ca2+ sequestration with thapsigargin, and cytoplasmic Ca2+ concentration was recorded with Fura-2 fluorometry. Compared to control neurons, the rate at which depolarization-induced Ca2+ transients resolved was increased in axotomized neurons after spinal nerve ligation, indicating accelerated PMCA function. Electrophysiological recordings showed that blockade of PMCA by vanadate prolonged the action potential afterhyperpolarization, and also decreased the rate at which neurons could fire repetitively. Conclusion We found that PMCA function is elevated in axotomized sensory neurons, which contributes to neuronal hyperexcitability. Accelerated PMCA function in the primary sensory neuron may contribute to the generation of neuropathic pain, and thus its modulation could provide a new pathway for peripheral treatment of post-traumatic neuropathic pain.

  11. Hardware-in-the-loop simulation and analysis of magnetic recording of nerve activity.

    Science.gov (United States)

    Jezernik, Saso

    2005-03-30

    The focus of the reported research was on examination of properties of a special toroidal arrangement for magnetic recording of nerve activity. Toroidal high permeability coil placed around a nerve trunk can be used to record voltage induced by magnetic field generated by ionic nerve currents associated with propagating action potentials. The properties were examined in hardware-in-the-loop simulations that were used to identify the input-output relationship of the recording arrangement in case of different simulated intra-axonal current amplitudes and conduction velocities. Based on the recorded data, a nonlinear dynamical model (Wiener model) of the recording arrangement was identified, and subsequently used for predicting the voltage waveform expected in actual magnetic recording. This waveform was also used to estimate the potential of the method with the respect to obtainable signal quality (signal-to-noise (S/N) ratios). The manuscript also contains new theoretical results for sensitivity of toroidal and electroneurographic recording arrangements to different disturbances like, for example, EMG pickup. It can be concluded that high S/N ratios, short length, and superior disturbance rejection of the toroidal magnetic recording arrangement can make magnetic recording an attractive alternative to acute and chronic electroneurographic recording techniques. PMID:15698669

  12. Patterned poly(chlorotrifluoroethylene) guides primary nerve cell adhesion and neurite outgrowth.

    Science.gov (United States)

    Saneinejad, S; Shoichet, M S

    2000-06-15

    Central nervous system (CNS) neurons, unlike those of the peripheral nervous system, do not spontaneously regenerate following injury. Recently it has been shown that in the developing CNS, a combination of cell-adhesive and cell-repulsive cues guide growing axons to their targets. We hypothesized that by mimicking these guidance signals, we could guide nerve cell adhesion and neurite outgrowth in vitro. Our objective was to direct primary nerve cell adhesion and neurite outgrowth on poly(chlorotrifluoroethylene) (PCTFE) surfaces by incorporating alternating patterns of cell-adhesive (peptide) and nonadhesive (polyethylene glycol; PEG) regions. PCTFE was surface-modified with lithium PEG-alkoxide, demonstrating the first report of metal-halogen exchange with an alkoxide and PCTFE. Titanium and then gold were sputtered onto PEG-modified films, using a shadow-masking technique that creates alternating patterns on the micrometer scale. PCTFE-Au regions then were modified with one of two cysteine-terminated laminin-derived peptides, C-GYIGSR or C-SIKVAV. Hippocampal neuron cell-surface interactions on homogeneously modified surfaces showed that neuron adhesion was decreased significantly on PEG-modified surfaces and was increased significantly on peptide-modified surfaces. Cell adhesion was greatest on CGYIGSR surfaces while neurite length was greatest on CSIKVAV surfaces and PLL/laminin positive controls, indicating the promise of peptides for enhanced cellular interactions. On patterned surfaces, hippocampal neurons adhered and extended neurites preferentially on peptide regions. By incorporating PEG and peptide molecules on the surface, we were able to simultaneously mimic cell-repulsive and cell-adhesive cues, respectively, and maintain the biopatterning of primary CNS neurons for over 1 week in culture. PMID:10756304

  13. Collagen biomaterial doped with colominic acid for cell culture applications with regard to peripheral nerve repair.

    Science.gov (United States)

    Bruns, Stephanie; Stark, Yvonne; Röker, Stefanie; Wieland, Martin; Dräger, Gerald; Kirschning, Andreas; Stahl, Frank; Kasper, Cornelia; Scheper, Thomas

    2007-09-15

    Colominic acid (CA) is a homopolymer of sialic acid residues and is solely composed of polymerised units of alpha-2,8-linked N-acetylneuraminic acid. CA is a specific derivative of polysialic acid (PSA), produced as the capsular polysaccharide of Escherichia coli K1 derived molecule of PSA. PSA in vivo plays a significant role in synaptic plasticity and neural development. The use of collagen materials doped with defined CA is presented for the cultivation of various cell lines relevant for possible applications in Tissue Engineering. First, the release behaviour under culture conditions of the collagen-based (C-CA) materials was investigated by thiobarbituric acid assay. Additionally, the established cell lines, PC-12 and immortalised Schwann cells (ISC), used for neurobiological and neurochemical studies and the model liver cell line Hep-G2 as indicator for biocompatibility testing, were cultured on the C-CA matrix. Cell proliferation (MTT-test) and cell adhesion (DAPI-staining) of the cell lines on the matrices were observed. Likewise, gene expression of the marker genes thyrosine hydroxylase for the PC-12 cells, and albumin, transferrin and CYP3A4 for the Hep-G2 cells was evaluated via RT-PCR. The results indicate that CA integration in established biomaterial constructs enhances cell proliferation and offers promising features as conduits additive in regarding peripheral nerve regeneration. PMID:17714819

  14. Relationship between interstitial cells of Cajal, fibroblast-like cells and inhibitory motor nerves in the internal anal sphincter.

    Science.gov (United States)

    Cobine, Caroline A; Hennig, Grant W; Kurahashi, Masaaki; Sanders, Kenton M; Ward, Sean M; Keef, Kathleen D

    2011-04-01

    Interstitial cells of Cajal (ICC) have been shown to participate in nitrergic neurotransmission in various regions of the gastrointestinal (GI) tract. Recently, fibroblast-like cells, which are positive for platelet-derived growth factor receptor ? (PDGFR?(+)), have been suggested to participate additionally in inhibitory neurotransmission in the GI tract. The distribution of ICC and PDGFR?(+) cell populations and their relationship to inhibitory nerves within the mouse internal anal sphincter (IAS) are unknown. Immunohistochemical techniques and confocal microscopy were therefore used to examine the density and arrangement of ICC, PDGFR?(+) cells and neuronal nitric-oxide-synthase-positive (nNOS(+)) nerve fibers in the IAS of wild-type (WT) and W/W ( v ) mice. Of the total tissue volume within the IAS circular muscle layer, 18% consisted in highly branched PDGFR?(+) cells (PDGFR?(+)-IM). Other populations of PDGFR?(+) cells were observed within the submucosa and along the serosal and myenteric surfaces. Spindle-shaped intramuscular ICC (ICC-IM) were present in the WT mouse IAS but were largely absent from the W/W ( v ) IAS. The ICC-IM volume (5% of tissue volume) in the WT mouse IAS was significantly smaller than that of PDGFR?(+)-IM. Stellate-shaped submucosal ICC (ICC-SM) were observed in the WT and W/W ( v ) IAS. Minimum surface distance analysis revealed that nNOS(+) nerve fibers were closely aligned with both ICC-IM and PDGFR?(+)-IM. An even closer association was seen between ICC-IM and PDGFR?(+)-IM. Thus, a close morphological arrangement exists between inhibitory motor neurons, ICC-IM and PDGFR?(+)-IM suggesting that some functional interaction occurs between them contributing to inhibitory neurotransmission in the IAS. PMID:21337122

  15. Antinociceptive activity of (-)-carvone: evidence of association with decreased peripheral nerve excitability.

    Science.gov (United States)

    Gonçalves, Juan Carlos Ramos; Oliveira, Fernando de Sousa; Benedito, Rubens Batista; de Sousa, Damião Pergentino; de Almeida, Reinaldo Nóbrega; de Araújo, Demetrius Antônio Machado

    2008-05-01

    (-)-Carvone is a monoterpene ketone that is the main active component of Mentha plant species like Mentha spicata. This study aimed to investigate the antinociceptive activity of (-)-carvone using different experimental models of pain and to investigate whether such effects might be involved in the nervous excitability elicited by others monoterpenes. In the acetic acid-induced writhing test, we observed that (-)-carvone-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg was administered. It was also demonstrated that (-)-carvone inhibited the licking response of the injected paw when 100 and 200 mg/kg was administered (i.p.) to mice in the first and second phases of the formalin test. Since naloxone (5 mg/kg, s.c.), an opioid antagonist, showed no influence on the antinociceptive action of (-)-carvone (100 mg/kg), this suggested nonparticipation of the opioid system in the modulation of pain induced by (-)-carvone. Such results were unlikely to be provoked by motor abnormality, since (-)-carvone-treated mice did not exhibit any performance alteration on the Rota-rod apparatus. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and observed that (-)-carvone (10 mM) was able to reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 50% from control recordings. We conclude that (-)-carvone has antinociceptive activity associated with decreased peripheral nerve excitability. PMID:18451538

  16. Effect of Human Umbilical Cord Mesenchymal Stem Cells Transplantation on Nerve Fibers of A Rat Model of Endometriosis

    Science.gov (United States)

    Chen, Yan; Li, Dong; Zhang, Zhe; Takushige, Natsuko; Kong, Bei-Hua; Wang, Guo-Yun

    2015-01-01

    Background Endometriosis is a common, benign, oestrogen-dependent, chronic gynaecological disorder associated with pelvic pain and infertility. Some researchers have identi?ed nerve ?bers in endometriotic lesions in women with endometriosis. Mesenchymal stem cells (MSCs) have attracted interest for their possible use for both cell and gene therapies because of their capacity for self-renewal and multipotentiality of differentiation. We investigated how human umbilical cord-MSCs (hUC-MSCs) could affect nerve ?bers density in endometriosis. Materials and Methods In this experimental study, hUC-MSCs were isolated from fresh human umbilical cord, characterized by flow cytometry, and then transplanted into surgically induced endometriosis in a rat model. Ectopic endometrial implants were collected four weeks later. The specimens were sectioned and stained immunohistochemically with antibodies against neuro?lament (NF), nerve growth factor (NGF), NGF receptor p75 (NGFRp75), tyrosine kinase receptor-A (Trk-A), calcitonin gene-related peptide (CGRP) and substance P (SP) to compare the presence of different types of nerve ?bers between the treatment group with the transplantation of hUC-MSCs and the control group without the transplantation of hUC-MSCs. Results There were significantly less nerve fibers stained with specific markers we used in the treatment group than in the control group (p<0.05). Conclusion MSC from human umbilical cord reduced nerve ?ber density in the treatment group with the transplantation of hUC-MSCs. PMID:25918595

  17. Nerve growth factor-induced changes in neural cell adhesion molecule (N-CAM) in PC12 cells.

    OpenAIRE

    Prentice, H M; Moore, S.E.; Dickson, J G; Doherty, P; Walsh, F. S.

    1987-01-01

    The effects of nerve growth factor (NGF) on the expression of neural cell adhesion molecule (N-CAM) in PC12 cells were determined. A quantitative immunoassay was used to show that NGF induces a 4- to 5-fold increase in relative N-CAM levels over a 3-day period. This increase could not be mimicked by cholera toxin suggesting that it is not a simple consequence of morphological differentiation. The changes in N-CAM levels induced by NGF were accompanied by changes in N-CAM molecular forms. The ...

  18. Nerve growth factor-treated, neurite-bearing PC12 cells continue to synthesize DNA

    International Nuclear Information System (INIS)

    Cultures of rat pheochromocytoma (PC12) cells treated with beta-nerve growth factor (NGF) for up to 15 days continue to synthesize DNA. The present study compares the extent of maintained DNA synthesis in cells with and without processes and asks whether the observed DNA synthesis in differentiated PC12 cells reflects either the continued division of the cells or the formation of polyploid cells, or both. PC12 cells were grown on tissue coverslips for various lengths of time with or without 50 ng/ml of beta-NGF and then assayed for DNA synthesis by [3H]thymidine labeling and autoradiography. In 8-day-old control cultures (no NGF), 30% of the cells had labeled nuclei after a 2-hr [3H]thymidine pulse. In contrast, in cultures treated for 8 days with NGF, only 7% of the cells were labeled (i.e., still synthesizing DNA). The fractions of process-bearing and non-process-bearing cells with labeled nuclei were identical. Even after 14 days in NGF, 7% of the cells with neurites were still synthesizing DNA during any 2-hr period. With continuous [3H]thymidine labeling in the presence of NGF from 8 to 13 days, nearly 70% of the cells with neurites were labeled. The presence of neurites induced by NGF does not preclude continued (albeit reduced) DNA synthesis in these PC12 cells. To determine the fate of this newly synthesized DNA, nuclei extracted from NGF-treated PC12 cells were analyzed for the cellular distribution of DNA by combined propidiur distribution of DNA by combined propidium iodine staining and flow microfluorimetry. NGF treatment resulted in a 3-fold increase in the number of G2+M/4N cells along with the appearance of 8N cells

  19. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation.

    Science.gov (United States)

    Darios, Emma S; Barman, Susan M; Orer, Hakan S; Morrison, Shaun F; Davis, Robert P; Seitz, Bridget M; Burnett, Robert; Watts, Stephanie W

    2015-05-01

    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101±4 to 63±3mm Hg during slow infusion of 5-HT (25?g/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865

  20. Crosstalk between Delta Opioid Receptor and Nerve Growth Factor Signaling Modulates Neuroprotection and Differentiation in Rodent Cell Models

    Directory of Open Access Journals (Sweden)

    Dwaipayan Sen

    2013-10-01

    Full Text Available Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve growth factor (NGF could induce expression of the delta opioid receptor gene (Oprd1, dor, mainly through PI3K/Akt/NF-?B signaling in PC12h cells. In this study, using two NGF-responsive rodent cell model systems, PC12h cells and F11 cells, we found the delta opioid neuropeptide [D-Ala2, D-Leu5] enkephalin (DADLE-mediated neuroprotective effect could be blocked by pharmacological reagents: the delta opioid antagonist naltrindole, PI3K inhibitor LY294002, MAPK inhibitor PD98059, and Trk inhibitor K252a, respectively. Western blot analysis revealed that DADLE activated both the PI3K/Akt and MAPK pathways in the two cell lines. siRNA Oprd1 gene knockdown experiment showed that the upregulation of NGF mRNA level was inhibited with concomitant inhibition of the survival effects of DADLE in the both cell models. siRNA Oprd1 gene knockdown also attenuated the DADLE-mediated neurite outgrowth in PC12h cells as well as phosphorylation of MAPK and Akt in PC12h and F11 cells, respectively. These data together strongly suggest that delta opioid peptide DADLE acts through the NGF-induced functional G protein-coupled Oprd1 to provide its neuroprotective and differentiating effects at least in part by regulating survival and differentiating MAPK and PI3K/Akt signaling pathways in NGF-responsive rodent neuronal cells.

  1. Use of hybrid chitosan membranes and human mesenchymal stem cells from the Wharton jelly of umbilical cord for promoting nerve regeneration in an axonotmesis rat model?

    OpenAIRE

    Ga?rtner, Andrea; Pereira, Tiago; Simo?es, Maria Joa?o; Armada-da-silva, Paulo As; Franc?a, Miguel L.; Sousa, Rosa; Bompasso, Simone; Raimondo, Stefania; Shirosaki, Yuki; Nakamura, Yuri; Hayakawa, Satoshi; Osakah, Akiyoshi; Porto, Beatriz; Lui?s, Ana Lu?cia; Vareja?o, Artur Sp

    2012-01-01

    Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to assess the effect on nerve regeneration, associating a hybrid chitosan membrane with non-differentiated human mesenchymal stem cells isolated from Wharton's jelly of umbilical cord, in peripheral nerve reconstruction after crush injury. Chromosome analysis on human mesenchymal stem cell line from Wharton's jelly was carried out and no structural alter...

  2. Age-Related Yield of Adipose-Derived Stem Cells Bearing the Low-Affinity Nerve Growth Factor Receptor

    OpenAIRE

    Raquel Cuevas-Diaz Duran; Maria Teresa González-Garza; Alejandro Cardenas-Lopez; Luis Chavez-Castilla; Delia Elva Cruz-Vega; Jorge E. Moreno-Cuevas

    2013-01-01

    Adipose-derived stem cells (ADSCs) are a heterogeneous cell population that may be enriched by positive selection with antibodies against the low-affinity nerve growth factor receptor (LNGFR or CD271), yielding a selective cell universe with higher proliferation and differentiation potential. This paper addresses the need for determining the quantity of ADSCs positive for the CD271 receptor and its correlation with donor's age. Mononuclear cells were harvested from the lower backs of 35 femal...

  3. Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric

    Directory of Open Access Journals (Sweden)

    Janssen Katherine T

    2006-10-01

    Full Text Available Abstract Background Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal ganglion cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the ?Geo reporter gene, to evaluate the time course of optic nerve degeneration and ganglion cell loss, respectively, in aging mice. Results Optic nerve degeneration, characterized by axon loss and gliosis is first apparent in mice between 8 and 9 months of age. Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe. Although nerve damage is typically bilateral, the progression of disease is asymmetric between the eyes of individual mice. Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region. Ganglion cell loss, as a function of the loss of ?Geo expression, is evident in some mice between 8 and 10 months of age and is prevalent in the majority of mice older than 10.5 months. Most eyes display a uniform loss of ganglion cells throughout the retina, but many younger mice exhibit focal loss of cells in sectors extending from the optic nerve head to the retinal periphery. Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal. Conclusion A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma.

  4. Analysis of spatial relationships in three dimensions: tools for the study of nerve cell patterning

    Directory of Open Access Journals (Sweden)

    Raven Mary A

    2008-07-01

    Full Text Available Abstract Background Multiple technologies have been brought to bear on understanding the three-dimensional morphology of individual neurons and glia within the brain, but little progress has been made on understanding the rules controlling cellular patterning. We describe new matlab-based software tools, now available to the scientific community, permitting the calculation of spatial statistics associated with 3D point patterns. The analyses are largely derived from the Delaunay tessellation of the field, including the nearest neighbor and Voronoi domain analyses, and from the spatial autocorrelogram. Results Our tools enable the analysis of the spatial relationship between neurons within the central nervous system in 3D, and permit the modeling of these fields based on lattice-like simulations, and on simulations of minimal-distance spacing rules. Here we demonstrate the utility of our analysis methods to discriminate between two different simulated neuronal populations. Conclusion Together, these tools can be used to reveal the presence of nerve cell patterning and to model its foundation, in turn informing on the potential developmental mechanisms that govern its establishment. Furthermore, in conjunction with analyses of dendritic morphology, they can be used to determine the degree of dendritic coverage within a volume of tissue exhibited by mature nerve cells.

  5. Comparative survival study of glial cells and cells composing walls of blood vessels in crustacean ventral nerve cord after photodynamic treatment

    Science.gov (United States)

    Kolosov, Mikhail S.; Shubina, Elena

    2015-03-01

    Photodynamic therapy is a prospective treatment modality of brain cancers. It is of importance to have information about relative survival rate of different cell types in nerve tissue during photodynamic treatment. Particularly, for development of sparing strategy of the photodynamic therapy of brain tumors, which pursuits both total elimination of malignant cells, which are usually of glial origin, and, at the same time, preservation of normal blood circulation as well as normal glial cells in the brain. The aim of this work was to carry out comparative survival study of glial cells and cells composing walls of blood vessels after photodynamic treatment, using simple model object - ventral nerve cord of crustacean.

  6. Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size.

    Science.gov (United States)

    Sulaiman, O A; Gordon, T

    2000-12-01

    Poor functional recovery after peripheral nerve injury has been generally attributed to inability of denervated muscles to accept reinnervation and recover from denervation atrophy. However, deterioration of the Schwann cell environment may play a more vital role. This study was undertaken to evaluate the effects of chronic denervation on the capacity of Schwann cells in the distal nerve stump to support axonal regeneration and to remyelinate regenerated axons. We used a delayed cross-suture anastomosis technique in which the common peroneal (CP) nerve in the rat was denervated for 0-24 weeks before cross-suture of the freshly axotomized tibial (TIB) and chronically denervated CP nerve stumps. Motor neurons were backlabeled with either fluoro-ruby or fluorogold 12 months later, to identify and count TIB motor neurons that regenerated axons into chronically denervated CP nerve stumps. Number, size, and myelination of regenerated sensory and motor axons were determined using light and electron microscopy. We found that short-term denervation of < or =4 weeks did not affect axonal regeneration but more prolonged denervation profoundly reduced the numbers of backlabeled motor neurons and axons in the distal nerve stump. Yet, atrophic Schwann cells retained their capacity to remyelinate regenerated axons. In fact, the axons were larger and well myelinated by long-term chronically denervated Schwann cells. These findings demonstrate a progressive inability of chronically denervated Schwann cells to support axonal regeneration and yet a sustained capacity to remyelinate the axons which do regenerate. Thus, axonal interaction can effectively switch the nonmyelinating phenotype of atrophic Schwann cells back into the myelinating phenotype. PMID:11102965

  7. Peripheral neurons and Schwann cells secrete plasminogen activator

    OpenAIRE

    1984-01-01

    The secretion of the protease plasminogen activator (PA) by cells of developing peripheral nerve was demonstrated. Fetal and early postnatal dorsal root ganglia were established in culture as explants or as individual neurons and Schwann cells. A fibrin overlay assay was used to visualize the locations of PA secretion. Fibrinolytic zones formed around the somata of explants and were skewed in the direction of maximal fiber outgrowth. Individual growth cones at the tips of long fasiculated fib...

  8. A structure-activity analysis of the variation in oxime efficacy against nerve agents

    International Nuclear Information System (INIS)

    A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (kr2) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and in vitro kr2 decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (r2 as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (kr2 · [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation toidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy

  9. Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration

    Science.gov (United States)

    Carriel, Víctor; Garrido-Gómez, Juan; Hernández-Cortés, Pedro; Garzón, Ingrid; García-García, Salomé; Sáez-Moreno, José Antonio; Sánchez-Quevedo, María del Carmen; Campos, Antonio; Alaminos, Miguel

    2013-04-01

    Objective. The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. Approach. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. Main results. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. Significance. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

  10. Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats.

    Science.gov (United States)

    Xia, Nan; Xu, Jin-Mei; Zhao, Nan; Zhao, Qing-Song; Li, Ming; Cheng, Zhi-Feng

    2015-06-15

    Neuropathy is observed in 50% of diabetic patients with diabetic foot. This study attempted to explore the potential role of human mesenchymal stem cells-umbilical cord blood (hMSCs-UC) in femoral nerve (FN) neuropathy. The model rats were established by one time administration of streptozotocin and empyrosis on the dorsal hind foot. At 3d, 7d, 14d after treatment with hMSCs-UC or saline through left femoral artery, the serum NGF was examined by ELISA; NF-200 expression in FN was evaluated by immunohistochemistry; the diameter and roundness of FN, the ratio of capillary and muscular fiber of gastrocnemius were calculated under light microscope; and neuronal degenerations, such as demyelization, axonal atrophy, and loose arrangement of nerve fibers, were observed by electronic microscope. The results showed that, in hMSCs-UC-treated model rats, serum NGF was increased with higher positive rate of NF-200. Although the difference in FN diameters was not established among groups, improvement of roundness of FN was confirmed with increase in the numbers of capillary in FN-innervated gastrocnemius; additionally, degenerative neuropathy was significantly improved. Importantly, the functional study of electroneurogram (ENG) showed that, slowed conduction of FN in model rats was significantly restored by hMSCs-CU treatment. These data suggested that hMSCs-UC-treatment partially reverse the neuronal degeneration and nerve function of FN, which might be contributed by the upregulation of NGF with dramatic angiogenesis in FN-innervated gastrocnemius, consequently reversing neuronal structure and function, preventing or curing foot ulceration. PMID:25916880

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

    DEFF Research Database (Denmark)

    MØllgård, Kjeld; Jespersen, A

    2010-01-01

    The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve fibers in the dorsal mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these nerve fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic nerve fibers with the majority adjacent to the most peripheral fibers (close to Schwann cells). We also show that both nerve fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryospreferentially migrate along autonomic nerve fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine nerve plexus.

  12. The search of the target of promotion: Phenylbenzoate esterase activities in hen peripheral nerve

    International Nuclear Information System (INIS)

    Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crude homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC50 of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbam including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds

  13. Effect of an exo-polysaccharide from the culture broth of Hericium erinaceus on enhancement of growth and differentiation of rat adrenal nerve cells

    OpenAIRE

    Park, Young Shik; Lee, Hyun Soo; Won, Moo Ho; Lee, Jin Ha; Lee, Shin Young; Lee, Hyeon Yong

    2002-01-01

    It was found that an exo-biopolymer (M.W. 1,000,000, molar ratio of 1.5:1.7:1.2:0.6:0.9, glucose:galactose:xylose:mannose:fructose, purity 99%) purified from the liquid culture broth of Hericium erinaceus mycelium enhanced the growth of rat adrenal nerve cells. The polymer also improved the extension of the neurites of PC12 cell. Its efficacy was found to be higher than those from known nerve growth factors such as Nerve Growth Factor (NGF) and Brain-Derived Nerve Factor (BDNF). The effect of...

  14. Giant cell arteritis mimicking infiltrative leptomeningeal disease of the optic nerves.

    Science.gov (United States)

    Kornberg, Michael D; Ratchford, John N; Subramaniam, Rathan M; Probasco, John C

    2015-01-01

    A 67-year-old man presented with several days of progressive, painless left eye vision loss. He reported mild jaw claudication but denied headache, scalp tenderness or constitutional symptoms. Examination revealed palpable temporal arteries, blurring of the left optic disc, and 20/100 vision in the left eye with mild relative afferent pupillary defect. Inflammatory markers were sent, and methylprednisolone was initiated for presumptive giant cell arteritis (GCA). Erythrocyte sedimentation rate was normal, however, and C reactive protein was only mildly elevated, prompting further investigation. Orbital MRI revealed nodular enhancement of the optic nerve sheaths bilaterally from optic nerve head to chiasm, raising concern for an infiltrative leptomeningeal process such as sarcoidosis or lymphoma. Methylprednisolone was temporarily stopped while a broad work up for inflammatory and neoplastic causes was pursued. Fluorodeoxyglucose-positron emission tomography ultimately revealed hypermetabolism in the temporal, ophthalmic and occipital arteries suggesting GCA, which was confirmed by temporal artery biopsy. Steroids were restarted, and the patient's vision stabilised. PMID:25858943

  15. A PET activation study of brush-evoked allodynia in patients with nerve injury pain.

    DEFF Research Database (Denmark)

    Witting, Nanna; Kupers, Ron

    2006-01-01

    Acute experimental brush-evoked allodynia induces a cortical activation pattern that differs from that typically seen during experimental nociceptive pain. In this study, we used positron emission tomography to measure changes in regional cerebral blood flow (rCBF) in patients with clinical allodynia. Nine patients with peripheral nerve injury were scanned during rest, brush-evoked allodynia, and brushing of normal contralateral skin. PET data were analyzed for the whole group and for single subjects. Allodynic stimulation activated the contralateral orbitofrontal cortex (BA 11) in every patient. Whereas normal brushing activated most strongly the contralateral insular cortex, allodynic brushing produced an ipsilateral activation in this area. Another important difference between normal and allodynic brushing was the absence of a contralateral primary somatosensory cortex (SI) activation during allodynic brushing. No thalamic activation was observed during allodynic or control brushing. Although no anterior cingulate cortex (ACC) activation could be demonstrated in the group analysis, single subject analysis revealed that four patients activated this region during brush-evoked allodynia. A direct post hoc comparison of brush -and allodynia-induced rCBF changes showed that allodynia was associated with significantly stronger activations in orbitofrontal cortex and ipsilateral insula whereas non-painful brushing more strongly activated SI and BA 5/7. These findings indicate that activity in the cortical network involved in the sensory-discriminative processing of nociceptive pain is downregulated in neuropathic pain. Instead, there is an upregulation of activity in the orbitofrontal and insular cortices, which is probably due to the stronger emotional load of neuropathic pain and higher computational demands of processing a mixed sensation of brush and pain.

  16. Blood pressure is maintained during dehydration by hypothalamic paraventricular nucleus-driven tonic sympathetic nerve activity.

    Science.gov (United States)

    Holbein, Walter W; Bardgett, Megan E; Toney, Glenn M

    2014-09-01

    Resting sympathetic nerve activity (SNA) consists primarily of respiratory and cardiac rhythmic bursts of action potentials. During homeostatic challenges such as dehydration, the hypothalamic paraventricular nucleus (PVN) is activated and drives SNA in support of arterial pressure (AP). Given that PVN neurones project to brainstem cardio-respiratory regions that generate bursting patterns of SNA, we sought to determine the contribution of PVN to support of rhythmic bursting of SNA during dehydration and to elucidate which bursts dominantly contribute to maintenance of AP. Euhydrated (EH) and dehydrated (DH) (48 h water deprived) rats were anaesthetized, bilaterally vagotomized and underwent acute PVN inhibition by bilateral injection of the GABA-A receptor agonist muscimol (0.1 nmol in 50 nl). Consistent with previous studies, muscimol had no effect in EH rats (n = 6), but reduced mean AP (MAP; P < 0.001) and integrated splanchnic SNA (sSNA; P < 0.001) in DH rats (n = 6). Arterial pulse pressure was unaffected in both groups. Muscimol reduced burst frequency of phrenic nerve activity (P < 0.05) equally in both groups without affecting the burst amplitude-duration integral (i.e. area under the curve). PVN inhibition did not affect the amplitude of the inspiratory peak, expiratory trough or expiratory peak of sSNA in either group, but reduced cardiac rhythmic sSNA in DH rats only (P < 0.001). The latter was largely reversed by inflating an aortic cuff to restore MAP (n = 5), suggesting that the muscimol-induced reduction of cardiac rhythmic sSNA in DH rats was an indirect effect of reducing MAP and thus arterial baroreceptor input. We conclude that MAP is largely maintained in anaesthetized DH rats by a PVN-driven component of sSNA that is neither respiratory nor cardiac rhythmic. PMID:24973410

  17. Leptin into the rostral ventral lateral medulla (RVLM augments renal sympathetic nerve activity and blood pressure

    Directory of Open Access Journals (Sweden)

    MariaJBarnes

    2014-08-01

    Full Text Available Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity. Therefore, leptin is emerging as a major contributor to the hypertensive state observed in obesity. Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem. The rostral ventral-lateral medulla (RVLM is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure. Previous studies from our laboratory have shown that neurons in the ventral lateral medulla express leptin receptors (ObRb. Our present study using pseudo-rabies multi-synaptic retrograde tract tracing and immunohistochemical methods revealed that neurons within the RVLM that send sympathetic projections to the kidney express leptin receptors. Acute microinjection of leptin (1 and 3µg; 40nL into the RVLM evoked a significant increase in Mean Arterial Pressure (MAP and renal sympathetic nerve activity (RSNA. When the 3µg dose of leptin was preceded with a leptin antagonist, (SLAN-4; 1ng, it attenuated the cardiovascular response of leptin. Taken together, these data suggest that leptin’s actions within the RVLM may influence blood pressure and renal sympathetic nerve activity.

  18. Release of chemical transmitters from cell bodies and dendrites of nerve cells.

    Science.gov (United States)

    De-Miguel, Francisco F; Nicholls, John G

    2015-07-01

    Papers in this issue concern extrasynaptic transmission, namely release of signalling molecules by exocytosis or diffusion from neuronal cell bodies, dendrites, axons and glia. Problems discussed concern the molecules, their secretion and importance for normal function and disease. Molecules secreted extrasynaptically include transmitters, peptides, hormones and nitric oxide. For extrasynaptic secretion, trains of action potentials are required, and the time course of release is slower than at synapses. Questions arise concerning the mechanism of extrasynaptic secretion: how does it differ from the release observed at synaptic terminals and gland cells? What kinds of vesicles take part? Is release accomplished through calcium entry, SNAP and SNARE proteins? A clear difference is in the role of molecules released synaptically and extrasynaptically. After extrasynaptic release, molecules reach distant as well as nearby cells, and thereby produce long-lasting changes over large volumes of brain. Such changes can affect circuits for motor performance and mood states. An example with clinical relevance is dyskinesia of patients treated with l-DOPA for Parkinson's disease. Extrasynaptically released transmitters also evoke responses in glial cells, which in turn release molecules that cause local vasodilatation and enhanced circulation in regions of the brain that are active. PMID:26009760

  19. Nerve growth induces 5-HT3 recognition sites in rat pheochromocytoma (PC12) cells

    International Nuclear Information System (INIS)

    In rat pheochromocytoma (PC12) cells, nerve growth factor (7S NGF) induced the expression of recognition sites that bind the specific 5-HT3 antagonist (S-) [3H] zacopride. Culturing PC12 cells for 8-12 days in the presence of 50 ng/ml NGF increased the density (Bmax) of (S-) [3H] zacopride binding sites in cell membranes (0-100,000 x g fraction) from 0 to 105 fmoles/mg protein. This binding exhibited high affinity for (S-) [3H] zacopride (Kd=0.8 nM), was specific (>95%), and was inhibited by 5-HT3 compounds with a rank of potency (quipazine>ICS 205-930 > GR38032F > BRL 24924?MDL 72222 > phenylbiguanide ? seroton-in > 2-methyl-serotonin > metoclopramide) which was distinct from neuroblastoma cells. Thus, NGF-differentiated PC12 cells possess a 5-HT3 receptor and should be useful to investigate its regulation and biochemical mechanism of action

  20. Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair

    Directory of Open Access Journals (Sweden)

    Dahlin Lars B

    2008-09-01

    Full Text Available Abstract Background A delay in surgical nerve repair results in impaired nerve function in humans, but mechanisms behind the weakened nerve regeneration are not known. Activating transcription factor 3 (ATF3 increases the intrinsic growth state of injured neurons early after injury, but the role of long-term changes and their relation to axonal outgrowth after a delayed nerve repair are not well understood. ATF3 expression was examined by immunohistochemistry in motor and sensory neurons and in Schwann cells in rat sciatic nerve and related to axonal outgrowth after transection and delayed nerve repair (repair 0, 30, 90 or 180 days post-injury. Expression of the neuronal cell adhesion molecule (NCAM, which is expressed in non-myelinating Schwann cells, was also examined. Results The number of neurons and Schwann cells expressing ATF3 declined and the length of axonal outgrowth was impaired if the repair was delayed. The decline was more rapid in motor neurons than in sensory neurons and Schwann cells. Regeneration distances over time correlated to number of ATF3 stained neurons and Schwann cells. Many neurofilament stained axons grew along ATF3 stained Schwann cells. If nerve repair was delayed the majority of Schwann cells in the distal nerve segment stained for NCAM. Conclusion Delayed nerve repair impairs nerve regeneration and length of axonal outgrowth correlates to ATF3 expression in both neurons and Schwann cells. Mainly non-myelinating Schwann cells (NCAM stained are present in distal nerve segments after delayed nerve repair. These data provide a neurobiological basis for the poor outcomes associated with delayed nerve repair. Nerve trunks should, if possible, be promptly repaired.

  1. Retinal Ganglion Cell Loss in a Rat Ocular Hypertension Model Is Sectorial and Involves Early Optic Nerve Axon Loss

    OpenAIRE

    Soto, Ileana; Pease, Mary E.; Son, Janice L.; Shi, Xiaohai; Quigley, Harry A; Marsh-Armstrong, Nicholas

    2011-01-01

    Retinal ganglion cell loss in a rat hypertension model is shown here to resemble that seen in the DBA/2J mouse glaucoma model. The shared early axon loss and characteristic sectorial degeneration pattern point to an optic nerve head insult.

  2. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

    Scientific Electronic Library Online (English)

    R.V., Tiradentes; J.G.P., Pires; N.F., Silva; A.G., Ramage; C.H., Santuzzi; H.A., Futuro Neto.

    2014-07-01

    Full Text Available Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full [...] antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

  3. Effect of Atorvastatin vs. Rosuvastatin on cardiac sympathetic nerve activity in non-diabetic patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Effects of statin therapy on cardiac sympathetic nerve activity in patients with chronic heart failure (CHF) have not previously been evaluated. To compare the effects of lipophilic atorvastatin and hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were already receiving standard therapy for CHF, were randomized to atorvastatin (n=32) or rosuvastatin (n=31). We evaluated cardiac sympathetic nerve activity by cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and after 6 months of treatment. There were no differences in the baseline characteristics of the 2 groups. In the rosuvastatin group, there were no changes in MIBG parameters, left ventricular ejection fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a significant increase in the delayed heart/mediastinum count ratio (2.18±0.4 vs. 2.36±0.4, P<0.0001), and the washout rate was significantly decreased (34.8±5.7 vs. 32.6±6.3%, P=0.0001) after 6 months of treatment compared with the baseline values. The plasma NT-proBNP level was also significantly decreased (729±858 vs. 558±747 pg/ml, P=0.0139). Lipophilic atorvastatin but not hydrophilic rosuvastatin improves cardiac sympathetic nerve activity in CHF patients with DCM. (author) patients with DCM. (author)

  4. Sacral nerve stimulation increases activation of the primary somatosensory cortex by anal canal stimulation in an experimental model.

    LENUS (Irish Health Repository)

    Griffin, K M

    2011-08-01

    Sacral and posterior tibial nerve stimulation may be used to treat faecal incontinence; however, the mechanism of action is unknown. The aim of this study was to establish whether sensory activation of the cerebral cortex by anal canal stimulation was increased by peripheral neuromodulation.

  5. THE EFFECTS OF POLARIZATION UPON THE STEEL WIRE-NITRIC ACID MODEL OF NERVE ACTIVITY.

    Science.gov (United States)

    Bishop, G H

    1927-11-20

    The active process in a short length of steel wire passivated by 65 per cent nitric acid has been observed under the influence of a polarizing current, and the form of the potential recorded by the cathode ray oscillograph. In the passive wire, 80 per cent of the total potential drop takes place at the anode, 20 per cent at the cathode. The change from active to passive states, as measured by the potential change, is very abrupt compared to the duration of activity and the potential curve at a point on the wire is probably almost rectangular. The duration of the refractory state is decreased at the anode and increased at the cathode, as in nerve. This fact is against the idea that reactivity after passivation results from a partial reduction of an oxide layer. Soft iron wire passivated by anodal polarization repassivates after activation in acid of a dilution that fails to passivate it initially. It soon becomes rhythmic with a very short refractory phase, and then reacts continuously. Such a wire exhibits a very sharp alternation between a dark brown oxide coat during activity, and a bright clean surface during passivation. A passive steel wire in nitric acid shows many of the characteristics of an inert electrode such as platinum, and it may be inferred that, superposed upon the primary passivation potential, there exists an electrode or oxidation-reduction potential equilibrium between the effects of the various constituents of the solution. It is suggested that the phenomena of nerve-like reactivity in this system may involve an alternation between two protective coatings of the steel wire. During activity, the surface becomes mechanically coated with a brown oxide. If this coating does not adhere, due to gas convection or to rapid solution of the oxide, passivation does not result. Under sufficiently intense oxidizing conditions, a second oxide coat may form in the interstices of the first, and cover the surface as the first coating dissolves off. This furnishes the electrochemical protection of passivation, which is followed by the gradual attainment of electrode equilibrium with the solution. PMID:19872388

  6. Protection of ginsenoside Rg1 on central nerve cell damage and the influence on neuron apoptosis.

    Science.gov (United States)

    Wang, Bo; He, Li; Cui, Bingzhou; Lv, Haixin

    2014-11-01

    This paper aimed to verify the function of ginsenoside in the repair of peripheral nerve injury through the model of sciatic nerve injury in rat. The method was to prepare the model of SD rat injury of sciatic nerve, and to conduct treatment with different dose of ginsenoside Rg1. At the same time, the control group was established. The regenerative repair, functional recovery and the situation of target organ, etc. were evaluated by neuromorphic metrology index, fluorescence gold retrograde tag, animal behavior index (sciatic nerve index). The result was the situation of nerve regenerative repair and functional recovery in high dose ginsenoside Rg1 group was obviously superior to other groups, the recovery of sciatic nerve index, target muscle, etc. were fine and mostly close to normal. It was concluded that ginsenoside Rg1 could effectively promote the regenerative repair of peripheral nerve injury, and accelerate the recovery of its nerve function. It could also promote the regeneration of peripheral nerve and the recovery of its nerve function. PMID:25410069

  7. Activation of afferent renal nerves modulates RVLM-projecting PVN neurons.

    Science.gov (United States)

    Xu, Bo; Zheng, Hong; Liu, Xuefei; Patel, Kaushik P

    2015-05-01

    Renal denervation for the treatment of hypertension has proven to be successful; however, the underlying mechanism/s are not entirely clear. To determine if preautonomic neurons in the paraventricular nucleus (PVN) respond to afferent renal nerve (ARN) stimulation, extracellular single-unit recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM)-projecting PVN (PVN-RVLM) neurons to the response elicited during stimulation of ARN. In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among these PVN-RVLM neurons, 84% (21/25) were activated by ARN stimulation. The baseline discharge rate was significantly higher in these neurons than those PVN-RVLM neurons not activated by ARN stimulation (16%, 4/25). The responsiveness of these neurons to baroreflex activation induced by phenylephrine and activation of cardiac sympathetic afferent reflex (CSAR) was also examined. Almost all of the PVN neurons that responded to ARN stimulation were sensitive to baroreflex (95%) and CSAR (100%). The discharge characteristics for nonevoked neurons (not activated by RVLM antidromic stimulation) showed that 23% of these PVN neurons responded to ARN stimulation. All the PVN neurons that responded to ARN stimulation were activated by N-methyl-d-aspartate, and these responses were attenuated by the glutamate receptor blocker AP5. These experiments demonstrated that sensory information originating in the kidney is integrated at the level of preautonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in the modulation of sympathetic outflow in disease states such as hypertension and heart failure. PMID:25637549

  8. Activation of codependent transcription factors is required for transcriptional induction of the vgf gene by nerve growth factor and Ras.

    Science.gov (United States)

    D'Arcangelo, G; Habas, R; Wang, S; Halegoua, S; Salton, S R

    1996-01-01

    Nerve growth factor (NGF) treatment of PC12 cells leads to the elaboration of a neuronal phenotype, including the induction of neuronally expressed genes such as vgf. To study vgf transcription, we have created chimeric vgf/beta-globin genes in which vgf promoter sequences drive the expression of the beta-globin reporter gene or of a chimeric beta-globin gene fused to 3' untranslated vgf gene sequences. We have found that the level of inducibility of the latter construct by NGF resembles that of the endogenous vgf gene. Using transient transfection of the chimeric reporter genes into PC12 cells, into PC12 subclones expressing activated or dominantly interfering mutant Ras proteins, and into PC12 variants expressing specific NGF receptor/Trk mutants, we show that transcriptional regulation of the vgf promoter by NGF is mediated through a Ras-dependent signaling pathway. By mutational analysis of the vgf promoter, we have identified three promoter elements involved in mediating transcriptional induction by NGF and Ras. In addition to the cyclic AMP-responsive element (CRE), which binds to ATF-1, ATF-2, and CRE-binding protein in PC12 nuclear extracts, a novel CCAAT element and its binding proteins were identified, which, like the CRE, is necessary but not sufficient for the Ras-dependent induction of the vgf gene by NGF. We also identify a G(S)G element unusually located between the TATA box and transcriptional start site, which binds the NGF- and Ras-induced transcription factor, NGFI-A, and amplifies the transcriptional response. Integrating data from studies of vgf promoter regulation and NGF signal transduction, we present a model for vgf gene induction in which transcriptional activation is achieved through the persistent, direct activation of multiple interacting transcription factors binding to CRE and CCAAT elements, coordinated with the delayed transcription factor action at a G(S)G element resulting from the induced expression of NGFI-A. PMID:8756618

  9. Low-frequency Electro-Acupuncture and Physical Exercise Decrease High Muscle Sympathetic Nerve Activity in Polycystic Ovary Syndrome

    Science.gov (United States)

    Elisabet Stener-Victorin (Institution of Neuroscience and Physiology)

    2009-06-03

    Context: We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity. Animal studies support the concept that low-frequency electro-acupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, may modulate the activity of the sympathetic nervous system. Objective: The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS. Design: Randomized controlled trial. Setting: Sahlgrenska University Hospital, Gothenburg, Sweden. Outcome Measures and Subjects: Twenty women with PCOS were randomly allocated to one of three groups; low-frequency EA (n=9), physical exercise (n=5) or to an untreated control (n=6) group during 16 weeks. Direct recordings of multiunit efferent postganglionic muscle sympathetic nerve activity (MSNA) in a muscle fascicle of the peroneal nerve before and following 16 weeks of treatment. Biometric, hemodynamic, endocrine and metabolic parameters were measured. Results: Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared to the untreated control group. Low-frequency EA group reduced sagittal diameter (P = 0.001), while physical exercise group reduced body weight (P = 0.004) and body mass index (BMI) (P = 0.004) as compared to the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P < 0.005) in the EA group. No correlation was found for BMI and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine and metabolic variables. Conclusions: For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for women with PCOS.

  10. Stem Cell Therapy for Erectile Dysfunction of Cavernous Nerve Injury Rats: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Shan, Haitao; Chen, Fengzhi; Zhang, Tao; He, Shuhua; Xu, Le; Wei, Anyang

    2015-01-01

    Introduction Stem cell treatment is a novel therapeutic strategy for erectile dysfunction (ED) patients with bilateral cavernous nerve injury (CNI). The relative animal studies provide important clues to design pre-clinical studies and clinical studies further in the future. Purpose This study aims to evaluate the effects and influential factors of stem cell transplantation on ED rats with CNI. Materials and Methods We searched PubMed and EBSCO databases published before April 30, 2014 for pre-clinical studies to evaluate the efficacy of stem cell transplantation in the treatment of ED rats with CNI. A systematic review and a planned subgroup analysis were performed to identify whether or not some certain influential factors could bring significant effects on stem cell treatment. Results 12 studies with 319 rats were enrolled in this meta-analysis. Pooled analysis results confirmed the efficacy of stem cell transplantation. Subgroup analysis results showed that treatment effects were not related to CNI models, follow-up time, stem cell species, stem cell sources, markers and delivery approaches in the transplantation. Uncultured stem cells were poorly effective compared with cultured stem cells. Periprostatic implantation (PPI) with acellular scaffolds could promote cavernous nerve regeneration, but was less effective for smooth muscle cell recovery. Stem cells modified by NGF or BDNF combined with udenafil/bFGF seemed to be more effective than those modified by BDNF alone. Conclusion This meta-analysis shows that stem cell therapy can be performed to recover erectile function. Future studies should focus on nerve restoration and vascular cell recovery. The synergistic actions of multiple growth factors following stem cell transplantation should also be considered as beneficial strategies to obtain preferable effects. PMID:25860455

  11. Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

    Science.gov (United States)

    Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

    2014-08-01

    Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-?-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-?-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

  12. The nerve growth factor receptor CD271 is crucial to maintain tumorigenicity and stem-like properties of melanoma cells

    OpenAIRE

    Redmer, T.; Welte, Y.; Behrens, D.; Fichtner, I.; Przybilla, D.; Wruck, W.; Yaspo, M. L.; Lehrach, H.; Schaefer, R.; Regenbrecht, C. R. A.

    2014-01-01

    BACKGROUND: Large-scale genomic analyses of patient cohorts have revealed extensive heterogeneity between individual tumors, contributing to treatment failure and drug resistance. In malignant melanoma, heterogeneity is thought to arise as a consequence of the differentiation of melanoma-initiating cells that are defined by cell-surface markers like CD271 or CD133. RESULTS: Here we confirmed that the nerve growth factor receptor (CD271) is a crucial determinant of tumorigenicity, stem-like p...

  13. Stem Cell Ophthalmology Treatment Study (SCOTS for retinal and optic nerve diseases: a preliminary report

    Directory of Open Access Journals (Sweden)

    Jeffrey N Weiss

    2015-01-01

    Full Text Available In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS. SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD and 20/4,000 Left Eye (OS. Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.

  14. Degradation of nerve gases by CLECS and cells: kinetics of heterogenous systems.

    Science.gov (United States)

    Hoskin, F C; Walker, J E; Stote, R

    1999-05-14

    We have reported the enzymatic hydrolysis of phosphoro- and phosphonofluoridates and phosphoro- and phosphonothiolates and -thionates by an organophosphorus hydrolase (OPH) from Pseudomonas diminuta. In screening for other microbial sources of nerve gas hydrolyzing enzymes, it would be convenient, indeed essential, to be able to determine such hydrolyses on intact cells. As a preliminary step to such screening we have measured the hydrolysis of O,O-diisopropyl S-(2-diisopropylaminoethyl) phosphorothiolate (Tetriso) and O,O-diethyl S-(2-ethylthioethyl) phosphorothiolate (Demeton-S; formerly Isosystox) by intact cells and sonicates. The purified OPH has also been cross-linked to itself (CLEC = cross-linked enzyme crystals) and this has also been tested for its ability to hydrolyze Tetriso and Demeton-S. The testing of such heterogenous systems by a spectrophotometric assay (Ellman) has required novel modifications. Our findings are that both Tetriso and Demeton-S are subject to intact-cell assay, that both are readily hydrolyzed by the CLEC-ed OPH without marked change in kinetics, but that at any given substrate concentration Tetriso is hydrolyzed much more rapidly. However, since Demeton-S is commercially available, this appears to be the substrate most suitable for screening for our final goal in a search for sources of enzymes to detoxify O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX). PMID:10421481

  15. Effects of Yogurt Containing Lactobacillus gasseri OLL2716 on Autonomic Nerve Activities and Physiological Functions

    Directory of Open Access Journals (Sweden)

    Kaiho Otomi

    2015-03-01

    Full Text Available The purpose of this study was to investigate the effects of yogurt containing Lactobacillus gasseri OLL2716 (LG21 on autonomic nerve activities, peripheral blood flow, skin condition (skin pig-mentations and moisture, saliva s-IgA and examination of quality of life (QOL. 20 healthy female volunteers (yogurt containing LG21 group: 10 people, yogurt containing Bifidobacterium (Bif group: 10 people were examined. The subjects ingested 100 g of yogurt twice daily for 4 weeks. Analysis was before and after 4 weeks dosage. By the effects for the autonomic nervous activity, parasympathetic increase was observed in the LG21 yogurt group, but was not significant increase. The LG21 yogurt was significantly increased on the peripheral blood flow. The LG21 yogurt was significantly increased on saliva s-IgA. The LG21 yogurt and Bif yogurt were significantly decrease on skin pigmentation. Also, LG21 yogurt was significantly increased on skin moisture. As a result of QOL questionnaire, incomplete evacuation, lower abdominal fullness, cold extremities and pimply or rough skin improved in LG21 yogurt and Bif yogurt after the administration period. These results suggest that the improvement effects of LG21 yogurt may be related to the activity of the parasympathetic nervous system.

  16. Attenuation of negative pain affect produced by unilateral spinal nerve injury in the rat following anterior cingulate cortex activation.

    Science.gov (United States)

    LaBuda, C J; Fuchs, P N

    2005-01-01

    The affective and the sensory dimensions of pain processing can be differentiated in humans through the use of questionnaires and verbal communication. It is difficult to dissociate these two components of pain processing in rodents, and an understanding of the underlying mechanisms for each component is unclear. The quantification of a novel behavioral response to a repeated noxious cutaneous stimulus together with a measurement of tactile allodynia in nerve-injured rats might be used to differentially explore the sensory and affective components of pain processing in the rat. The present study utilized electrical stimulation of the anterior cingulate cortex, a structure implicated in affective pain processing but not sensory processing, in nerve-injured rats (L5 spinal nerve ligation) and found that the aversive quality of noxious cutaneous hindpaw stimulation was attenuated. There were no effects on sensory processing, because anterior cingulate cortex stimulation did not produce an anti-allodynic effect in L5 spinal nerve ligation animals. Furthermore, anterior cingulate cortex stimulation in animals with bilateral ventrolateral periaqueductal gray area lesions did not affect tactile sensitivity in L5 spinal nerve ligation rats, indicating that an endogenous pain suppression system was not likely activated by anterior cingulate cortex stimulation. However, bilateral ventrolateral periaqueductal gray area lesions in L5 spinal nerve ligation rats blocked the effect produced by anterior cingulate cortex stimulation in the place escape/avoidance paradigm. Specifically, these animals avoided noxious stimulation of the allodynic paw significantly more than anterior cingulate cortex-stimulated, sham or incomplete ventrolateral periaqueductal gray area-lesioned, L5 spinal nerve ligation animals. These findings provide the first quantified report that the activation of the anterior cingulate cortex reduced the aversive quality of repeated noxious tactile stimulation in nerve-injured animals without interfering with normal sensory processing. This effect might require the presence of an intact ventrolateral periaqueductal gray area. It is concluded that the selective manipulation of the anterior cingulate cortex has different effects on pain affect and sensory processing in a rodent model of neuropathic pain. PMID:16404776

  17. Nerves and Anesthesia: A physics perspective on medicine

    CERN Document Server

    Heimburg, Thomas

    2014-01-01

    We present a recent theory for nerve pulse propagation and anesthesia and argue that both nerve activity and the action of anesthetics can be understood on the basis of simple physical laws. It was found experimentally that biological membranes melt from a solid state to a liquid state just below physiological temperature. Such melting processes have a profound influence on the physical properties of cell membranes. They make it possible for mechanical pulses (solitons) to travel along nerve axons. In these pulses, a region of solid phase travels in the liquid nerve membrane. These pulses display many properties associated with the action potential in nerves. Both general and local anesthetics lower melting temperatures of membranes. Thus, they make it more difficult to excite the nerve membrane. Since hydrostatic pressure increases melting temperatures, it counteracts anesthesia. This theory has the virtue of providing a simple explanation of the famous Meyer-Overton correlation, which states that the effect...

  18. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    International Nuclear Information System (INIS)

    Research highlights: ? Extracellular Nm23H1 stimulates nerve growth. ? Extracellular Nm23H1 provides pathfinding cues to growth cones. ? The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. ? The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  19. Enhancement of the nerve growth factor-mediated neurite outgrowth from PC12D cells by Chinese and Paraguayan medicinal plants.

    Science.gov (United States)

    Li, P; Matsunaga, K; Ohizumi, Y

    1999-07-01

    It is very important to search for natural compounds possessing nerve growth factor (NGF)-potentiating activity. Extracts of 7 Chinese and 10 Paraguayan medicinal plants were examined for their effects on the NGF-mediated neurite outgrowth from PC12D cells to evaluate their NGF-potentiating activities. In the methanol extracts, Gymmopteris rufa (LINN.) BERNH, Ruta graveolens LINN. and Picrorhiza scrophulariiflora PENNELL markedly increased the proportion of neurite-bearing cells. In the case of ethyl acetate fractions, Equisetum giganteum LINN. produced the most powerful enhancement of the proportion of the neurite-bearing cells, and the activities were in the following decreasing order: Equisetum giganteum LINN., Gymmopteris rufa (LINN.) BERNH, Ruta graveolens LINN., and Picrorhiza scrophulariiflora PENNELL. In the water fractions, Imperata cylindrica, Ginseng Radix, Gymmopteris rufa (LINN.) BERNH, Gochnatia polymorpha (LESS) CAB and Picrorhiza scrophulariiflora PENNELL caused a weak enhancement of the proportion of PC12D cells with neurites. Of all the extracts and fractions, the methanol extract of Picrorhiza scrophulariiflora PENNELL induced the longest neurites in PC12D cells. In the ethyl acetate and water fractions of Nardostachys chinensis, long neurites were observed although only a small proportion of PC12D cells had neurites. On the other hand, in the ethyl acetate fraction of Equisetum gigantheum LINN., while the length of the neurites was short, the proportion of neurite-bearing cells was largest among all the extracts and fractions. PMID:10443479

  20. Regeneração de nervos periféricos: terapia celular e fatores neurotróficos / Peripheral nerve regeneration: cell therapy and neurotrophic factors

    Scientific Electronic Library Online (English)

    Alessandra Deise, Sebben; Martina, Lichtenfels; Jefferson Luis Braga da, Silva.

    Full Text Available Traumatismos em nervos periféricos resultam na perda de função do órgão inervado e raramente apresentam recuperação sem a intervenção cirúrgica. Diversas técnicas cirúrgicas são passíveis de serem empregadas para o reparo nervoso. Dentre elas, ressalta-se o uso da técnica de tubulização, podendo ser [...] acrescentados fatores com capacidade regenerativa na câmara. A terapia celular e engenharia de tecidos surgem como uma alternativa para estimular e auxiliar a regeneração de nervos periféricos. Portanto, o objetivo desta revisão é fornecer um levantamento e uma análise de estudos experimentais e clínicos, quanto aos resultados obtidos, que utilizam a terapia celular e engenharia de tecidos como ferramentas para otimizar o processo de regeneração. Os artigos utilizados são oriundos de bases de dados científicas LILACS e Medline, através de pesquisas realizadas no PubMed e SciELO. Artigos sobre o uso de células-tronco, células de Schwann, fatores de crescimento, colágeno, laminina e plasma rico em plaquetas no reparo de nervos periféricos foram sintetizados ao longo da revisão. Com base nos diversos estudos pode-se concluir que a utilização de células-tronco derivadas de diferentes fontes apresentam resultados promissores na regeneração nervosa, pois estas possuem capacidade de diferenciação neuronal, demonstrando, assim, resultados funcionais eficazes. O uso de tubos acrescidos de elementos bioativos com liberação controlada também otimiza o reparo nervoso, promovendo uma maior mielinização e crescimento axonal dos nervos periféricos. Outro tratamento promissor é o uso de plasma rico em plaquetas, que, além de liberar fatores de crescimento importantes no reparo nervoso, ainda serve como um carreador para fatores exógenos estimulando a proliferação de células específicas no reparo de nervo periférico. Abstract in english Peripheral nerve trauma results in functional loss in the innervated organ, and recovery without surgical intervention is rare. Many surgical techniques can be used for nerve repair. Among these, the tubulization technique can be highlighted: this allows regenerative factors to be introduced into th [...] e chamber. Cell therapy and tissue engineering have arisen as an alternative for stimulating and aiding peripheral nerve regeneration. Therefore, the aim of this review was to provide a survey and analysis on the results from experimental and clinical studies that used cell therapy and tissue engineering as tools for optimizing the regeneration process. The articles used came from the LILACS, Medline and SciELO scientific databases. Articles on the use of stem cells, Schwann cells, growth factors, collagen, laminin and platelet-rich plasma for peripheral nerve repair were summarized over the course of the review. Based on these studies, it could be concluded that the use of stem cells derived from different sources presents promising results relating to nerve regeneration, because these cells have a capacity for neuronal differentiation, thus demonstrating effective functional results. The use of tubes containing bioactive elements with controlled release also optimizes the nerve repair, thus promoting greater myelination and axonal growth of peripheral nerves. Another promising treatment is the use of platelet-rich plasma, which not only releases growth factors that are important in nerve repair, but also serves as a carrier for exogenous factors, thereby stimulating the proliferation of specific cells for peripheral nerve repair.

  1. Regeneração de nervos periféricos: terapia celular e fatores neurotróficos Peripheral nerve regeneration: cell therapy and neurotrophic factors

    Directory of Open Access Journals (Sweden)

    Alessandra Deise Sebben

    2011-01-01

    Full Text Available Traumatismos em nervos periféricos resultam na perda de função do órgão inervado e raramente apresentam recuperação sem a intervenção cirúrgica. Diversas técnicas cirúrgicas são passíveis de serem empregadas para o reparo nervoso. Dentre elas, ressalta-se o uso da técnica de tubulização, podendo ser acrescentados fatores com capacidade regenerativa na câmara. A terapia celular e engenharia de tecidos surgem como uma alternativa para estimular e auxiliar a regeneração de nervos periféricos. Portanto, o objetivo desta revisão é fornecer um levantamento e uma análise de estudos experimentais e clínicos, quanto aos resultados obtidos, que utilizam a terapia celular e engenharia de tecidos como ferramentas para otimizar o processo de regeneração. Os artigos utilizados são oriundos de bases de dados científicas LILACS e Medline, através de pesquisas realizadas no PubMed e SciELO. Artigos sobre o uso de células-tronco, células de Schwann, fatores de crescimento, colágeno, laminina e plasma rico em plaquetas no reparo de nervos periféricos foram sintetizados ao longo da revisão. Com base nos diversos estudos pode-se concluir que a utilização de células-tronco derivadas de diferentes fontes apresentam resultados promissores na regeneração nervosa, pois estas possuem capacidade de diferenciação neuronal, demonstrando, assim, resultados funcionais eficazes. O uso de tubos acrescidos de elementos bioativos com liberação controlada também otimiza o reparo nervoso, promovendo uma maior mielinização e crescimento axonal dos nervos periféricos. Outro tratamento promissor é o uso de plasma rico em plaquetas, que, além de liberar fatores de crescimento importantes no reparo nervoso, ainda serve como um carreador para fatores exógenos estimulando a proliferação de células específicas no reparo de nervo periférico.Peripheral nerve trauma results in functional loss in the innervated organ, and recovery without surgical intervention is rare. Many surgical techniques can be used for nerve repair. Among these, the tubulization technique can be highlighted: this allows regenerative factors to be introduced into the chamber. Cell therapy and tissue engineering have arisen as an alternative for stimulating and aiding peripheral nerve regeneration. Therefore, the aim of this review was to provide a survey and analysis on the results from experimental and clinical studies that used cell therapy and tissue engineering as tools for optimizing the regeneration process. The articles used came from the LILACS, Medline and SciELO scientific databases. Articles on the use of stem cells, Schwann cells, growth factors, collagen, laminin and platelet-rich plasma for peripheral nerve repair were summarized over the course of the review. Based on these studies, it could be concluded that the use of stem cells derived from different sources presents promising results relating to nerve regeneration, because these cells have a capacity for neuronal differentiation, thus demonstrating effective functional results. The use of tubes containing bioactive elements with controlled release also optimizes the nerve repair, thus promoting greater myelination and axonal growth of peripheral nerves. Another promising treatment is the use of platelet-rich plasma, which not only releases growth factors that are important in nerve repair, but also serves as a carrier for exogenous factors, thereby stimulating the proliferation of specific cells for peripheral nerve repair.

  2. Two adjacent promoter elements mediate nerve growth factor activation of the c-fos gene and bind distinct nuclear complexes.

    OpenAIRE

    Visvader, J; Sassone-Corsi, P; Verma, I M

    1988-01-01

    Protooncogene fos is rapidly and transiently induced by nerve growth factor (NGF) in rat pheochromocytoma PC12 cells. Two adjacent promoter elements have been identified to mediate the NGF response. One element colocalizes with the serum response element (SRE) centered at position -308, previously shown to confer inducibility by serum, phorbol 12-myristate 13-acetate, and epidermal growth factor, whereas the other element, termed SRE-2, maps approximately 20 base pairs downstream of the SRE a...

  3. Cells of origin of the branches of the facial nerve: a retrograde HRP study in the rabbit.

    Science.gov (United States)

    Baisden, R H; Woodruff, M L; Whittington, D L; Baker, D C; Benson, A E

    1987-02-01

    The origin of different branches of the facial nerve in the rabbit was determined by using retrograde transport of HRP. Either the proximal stump of specific nerves was exposed to HRP after transection, or an injection of the tracer was made into particular muscles innervated by a branch of the facial nerve. A clear somatotopic pattern was observed. Those branches which innervate the rostral facial musculature arise from cells located in the lateral and intermediate portions of the nuclear complex. Orbital musculature is supplied by neurons in the dorsal portion of the complex, with the more rostral orbital muscles receiving input from more laterally located cells while the caudal orbital region receives innervation from more medial regions of the dorsal facial nucleus. The rostral portion of the ear also receives innervation from cells located in the dorsomedial part of the nucleus, but the caudal aspect of the ear is supplied exclusively by cells located in medial regions. The cervical platysma, the platysma of the lower jaw, and the deep muscles (i.e., digastric and stylohyoid) receive input from cells topographically arranged in the middle and ventral portions of the nuclear complex. It is proposed that the topographic relationship between the facial nucleus and branches of the facial nerve reflects the embryological derivation of the facial muscles. Those muscles that develop from the embryonic sphincter colli profundus layer are innervated by lateral and dorsomedial portions of the nuclear complex. The muscles derived from the embryonic platysma layer, including the deep musculature, receive their input from mid to ventral regions of the nuclear complex. PMID:3578081

  4. Celastrol supports survival of retinal ganglion cells injured by optic nerve crush.

    Science.gov (United States)

    Kyung, Haksu; Kwong, Jacky M K; Bekerman, Vlad; Gu, Lei; Yadegari, Daniel; Caprioli, Joseph; Piri, Natik

    2015-06-01

    The present study evaluates the effect of celastrol on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). Celastrol, a quinine methide triterpene extracted from the perennial vine Tripterygium wilfordii (Celastraceae), has been identified as a potential neuroprotective candidate in a comprehensive drug screen against various neurodegenerative diseases. Two weeks after ONC, the average density of remaining RGCs in retinas of animals treated with daily intraperitoneal (i.p.) injections of celastrol (1mg/kg) was approximately 1332cells/mm(2), or 40.8% of the Celastrol/Control group. In retinas of the Vehicle/ONC group about 381RGCs/mm(2) were counted, which is 9.6% of the total number of RGCs in the DMSO/Control group. This corresponds to approximately a 250% increase in RGC survival mediated by celastrol treatment compared to Vehicle/ONC group. Furthermore, the average RGC number in retinas of ONC animals treated with a single intravitreal injection of 1mg/kg or 5mg/kg of celastrol was increased by approximately 80% (760RGCs/mm(2)) and 78% (753RGCs/mm(2)), respectively, compared to Vehicle/ONC controls (422cells/mm(2)). Injection of 0.2mg/kg of celastrol had no significant effect on cell survival, with the average number of RGCs being 514cells/mm(2) in celastrol-treated animals versus 422cells/mm(2) in controls. The expression levels of Hsp70, Hsf1, Hsf2, HO-1 and TNF-alpha in the retina were analyzed to evaluate the roles of these proteins in the celastrol-mediated protection of injured RGCs. No statistically significant change in HO-1, Hsf1 and Hsp70 levels was seen in animals with ONC. An approximately 2 fold increase in Hsf2 level was observed in celastrol-treated animals with or without injury. Hsf2 level was also increased 1.8 fold in DMSO-treated animals with ONC injury compared to DMSO-treated animals with no injury suggesting that Hsf2 induction has an injury-induced component. Expression of TNF-alpha in retinas of celastrol-treated uninjured and ONC animals was reduced by approximately 2 and 1.5 fold compared to vehicle treated animals, respectively. The observed results suggest that mechanisms underlying celastrol?s RGC protective effect are associated with inhibition of TNF-alpha-mediated cell death. PMID:25813825

  5. Long term recovery of median nerve repair using laser-activated chitosan adhesive films.

    Science.gov (United States)

    Barton, Matthew J; Morley, John W; Stoodley, Marcus A; Shaikh, Sumaiya; Mahns, David A; Lauto, Antonio

    2015-03-01

    Sutures remain the standard peripheral nerve repair technique, whether applied directly or indirectly to nerve tissue. Unfortunately, significant postoperative complications can result, such as inflammation, neuroma formation and foreign body reactions. Photochemical-tissue-bonding (PTB) using rose Bengal (RB) integrated into a chitosan bioadhesive is an alternative nerve repair device that removes the need for sutures. Rats were arranged into three groups: RB-chitosan adhesives-repair, end-to-end epineural suture-repair (surgical standard) and sham laser-irradiated control. Groups were compared through histological assessment, electrophysiological recordings and grip motor strength. RB-chitosan adhesive repaired nerves displayed comparable results when compared to the standard suture-repair based on histological and electrophysiological findings. Functionally, RB-chitosan adhesive was associated with a quicker and more pronounced recovery of grip force when compared to the suture-repair. PMID:24132983

  6. Arbitrary units are a composite and useful measure of muscle sympathetic nerve activity

    International Nuclear Information System (INIS)

    In humans, the muscle sympathetic nerve activity (MSNA) signal is challenging to detect, record and analyze. Several methods exist that attempt to capture the latent construct of MSNA. We directly compared the performance of five MSNA parameters: burst frequency, burst incidence, median burst amplitude, arbitrary units (AU) and fractal dimension (FD). The MSNA signal was recorded in 33 subjects for ?30 min before, during and after the application of a graded cold pressor test stimulus at 18 °C, 10 °C and 2 °C in random order with an adequate wash-out period. Using coefficient of variation, Shannon's entropy and principal component analysis, we observed that these five parameters defined two physical and conceptual domains of MSNA—frequency and amplitude. Since AU combines information from both these domains, we observed that it explained maximum inter-subject and inter-experimental segment variation. FD did not explain the inter-subject variability and was identified as a unique parameter in the factor analysis. Epidemiological studies that attempt to quantify MSNA may consistently use AU as the parameter for quantification of MSNA

  7. Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

    Science.gov (United States)

    Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

    2002-01-01

    The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.

  8. Lumbar sympathetic nerve activity and hindquarter blood flow during REM sleep in rats.

    Science.gov (United States)

    Miki, Kenju; Oda, Michiyo; Kamijyo, Nozomi; Kawahara, Kazumi; Yoshimoto, Misa

    2004-05-15

    The present study aimed to investigate the response of lumbar sympathetic nerve activity (LSNA) to the onset of rapid eye movement (REM) sleep and its contribution to the regulation of muscle blood flow during REM sleep in rats. Electrodes for the measurements of LSNA, electroencephalogram, electromyogram and electrocardiogram and a Doppler flow cuff for the measurements of blood flow in the common iliac and mesenteric arteries, also catheters for the measurements of systemic arterial and central venous pressures were implanted chronically. REM sleep resulted in a step increase in LSNA, by 22 +/- 9% (mean +/-S.E.M., P arterial pressure, reaching a maximum value of 8.1 +/- 2.0 mmHg (P lumbar sympathectomy blunted the reduction of iliac blood flow induced by the onset of REM sleep. The present observations suggest that the onset of REM sleep appears to be associated with a vasodilation in viscera and a vasoconstriction in skeletal muscle, such that systemic arterial pressure increases during REM sleep in rats. PMID:15020688

  9. Neuromuscular activity of Bothrops neuwiedi pauloensis snake venom in mouse nerve-muscle preparations

    Directory of Open Access Journals (Sweden)

    A. M. Durigon

    2005-03-01

    Full Text Available The pharmacological effects of Bothrops neuwiedi pauloensis venom on mouse phrenic nerve-diaphragm (PND preparations were studied. Venom (20 mug/ml irreversibly inhibited indirectly evoked twitches in PND preparations (60 ± 10% inhibition, mean ± SEM; p<0.05; n=6. At 50 mug/ml, the venom blocked indirectly and directly (curarized preparations evoked twitches in mouse hemidiaphragms. In the absence of Ca2+, venom (50 mug/ml, produced partial blockade only after an 80 min incubation, which reached 40.3 ± 7.8% (p<0.05; n=3 after 120 min. Venom (20 mug/ml increased (25 ± 2%, p< 0.05 the frequency of giant miniature end-plate potentials in 9 of 10 end-plates after 30 min and the number of miniature end-plate potentials which was maximum (562 ± 3%, p<0.05 after 120 min. During the same period, the resting membrane potential decreased from - 81 ± 1.4 mV to - 41.3 ± 3.6 mV 24 fibers; p<0.01; n=4 in the end-plate region and from - 77.4 ± 1.4 to -44.6 ± 3.9 mV (24 fibers; p<0.01; n=4 in regions distant from the end-plate. These results indicate that B. n. pauloensis venom acts primarily at presynaptic sites. They also suggest that enzymatic activity may be involved in this pharmacological action.

  10. Skin sympathetic nerve activity in humans during exposure to emotionally-charged images: sex differences

    Directory of Open Access Journals (Sweden)

    RachaelBrown

    2014-03-01

    Full Text Available While it is known that anxiety or emotional arousal affects skin sympathetic nerve activity (SSNA, the galvanic skin response (GSR is the most widely used parameter to infer increases in SSNA during stress or emotional studies. We recently showed that SSNA provides a more sensitive measure of emotional state than effector-organ responses. The aim of the present study was to assess whether there are gender differences in the responses of SSNA and other physiological parameters such as blood pressure, heart rate, skin blood flow and sweat release, while subjects viewed neutral or emotionally-charged images from the International Affective Picture System. Changes in SSNA were assessed using microneurography in twenty subjects (ten male and ten female. Blocks of positively-charged (erotica or negatively-charge images (mutilation were presented in a quasi-random fashion, following a block of neutral images, with each block containing fifteen images and lasting two minutes. Images of both erotica and mutilation caused significant increases in SSNA, with increases being greater for males viewing erotica and greater for females viewing mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not significantly different than those produced by viewing neutral images and were not always consistent with the SSNA increases. We conclude that SSNA increases with both positively-charged and negatively-charged emotional images, yet sex differences are present.

  11. Skin sympathetic nerve activity in humans during exposure to emotionally-charged images: sex differences.

    Science.gov (United States)

    Brown, Rachael; Macefield, Vaughan G

    2014-01-01

    While it is known that anxiety or emotional arousal affects skin sympathetic nerve activity (SSNA), the galvanic skin response (GSR) is the most widely used parameter to infer increases in SSNA during stress or emotional studies. We recently showed that SSNA provides a more sensitive measure of emotional state than effector-organ responses. The aim of the present study was to assess whether there are gender differences in the responses of SSNA and other physiological parameters such as blood pressure, heart rate, skin blood flow and sweat release, while subjects viewed neutral or emotionally-charged images from the International Affective Picture System (IAPS). Changes in SSNA were assessed using microneurography in 20 subjects (10 male and 10 female). Blocks of positively-charged (erotica) or negatively-charge images (mutilation) were presented in a quasi-random fashion, following a block of neutral images, with each block containing 15 images and lasting 2 min. Images of both erotica and mutilation caused significant increases in SSNA, with increases being greater for males viewing erotica and greater for females viewing mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not significantly different than those produced by viewing neutral images and were not always consistent with the SSNA increases. We conclude that SSNA increases with both positively-charged and negatively-charged emotional images, yet sex differences are present. PMID:24678303

  12. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity

    International Nuclear Information System (INIS)

    Src family kinases are involved in transducing growth factor signals for cellular differentiation and proliferation in a variety of cell types. The activity of all Src family kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-terminal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Src family kinases in neuronal differentiation. Pretreatment of PC12 cells with the Src family kinase inhibitor, PP1, blocked NGF-induced activation of SFKs and obliterated neurite outgrowth. To confirm a role for CSK and specific isoforms of SFKs in neuronal differentiation, we overexpressed active and catalytically dead CSK in the rat pheochromocytoma cell line, PC12. CSK overexpression caused a profound inhibition of NGF-induced activation of FYN, YES, RAS, and ERK and inhibited neurite outgrowth, NGF-stimulated integrin-directed migration and blocked the NGF-induced conversion of GDP-RAC to its GTP-bound active state. CSK overexpression markedly augmented the activation state of AKT following NGF stimulation. In contrast, kinase-dead CSK augmented the activation of FYN, RAS, and ERK and increased neurite outgrowth. These data suggest a distinct requirement for CSK in the regulation of NGF/TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation

  13. Activation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells.

    LENUS (Irish Health Repository)

    Irnaten, Mustapha

    2009-01-01

    The lamina cribrosa (LC) region of the optic nerve head is considered the primary site of damage in glaucomatous optic neuropathy. Resident LC cells have a profibrotic potential when exposed to cyclical stretch. However, the mechanosensitive mechanisms of these cells remain unknown. Here the authors investigated the effects of membrane stretch on cell volume change and ion channel activity and examined the associated changes in intracellular calcium ([Ca(2+)](i)).

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

    OpenAIRE

    Fu, Liang-wu; Longhurst, John C.

    2013-01-01

    Thinly myelinated A?-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 ische...

  15. Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

    OpenAIRE

    Vianna, Lauro C.; Hart, Emma C.; Fairfax, Seth T.; Charkoudian, Nisha; Joyner, Michael J.; Fadel, Paul J.

    2012-01-01

    The sympathetic nervous system is critical for the beat-to-beat regulation of arterial blood pressure (BP). Although studies have examined age- and sex-related effects on BP control, findings are inconsistent and limited data are available in postmenopausal women. In addition, the majority of studies have focused on time-averaged responses without consideration for potential beat-to-beat alterations. Thus we examined whether the ability of muscle sympathetic nerve activity (MSNA) to modulate ...

  16. Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally-charged images

    OpenAIRE

    RachaelBrown; LukeHenderson

    2012-01-01

    The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally-charged ...

  17. Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images

    OpenAIRE

    Brown, Rachael; James, Cheree; Henderson, Luke A.; Macefield, Vaughan G.

    2012-01-01

    The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged ...

  18. [Tissue engineering of erectile nerves].

    Science.gov (United States)

    May, F; Weidner, N; Matiasek, K; Vroemen, M; Mrva, T; Caspers, C; Henke, J; Brill, T; Lehmer, A; Blesch, A; Erhardt, W; Gänsbacher, B; Hartung, R

    2004-10-01

    Dissection of the cavernous nerves eliminates spontaneous erections and may lead to irreversible erectile dysfunction due to degeneration of cavernous tissue. Novel procedures to reconstruct penile innervation include cavernous nerve interposition grafting and neurotrophic treatments to revitalize penile neural input, evaluated thus far in various preclinical models of cavernous nerve injury. Schwann cells crucially contribute to successful axonal regeneration by mechanical and paracrine mechanisms in the injured nerve, and Schwann cells seeded into guidance channels have been successfully employed to support regeneration in animal models of cavernous nerve injury. Gene therapy, tissue engineering, and reconstructive techniques have been combined to deliver neurotrophic factors and recover erectile function. PMID:15549162

  19. Activation of Satellite Glial Cells in Rat Trigeminal Ganglion after Upper Molar Extraction

    International Nuclear Information System (INIS)

    The neurons in the trigeminal ganglion (TG) are surrounded by satellite glial cells (SGCs), which passively support the function of the neurons, but little is known about the interactions between SGCs and TG neurons after peripheral nerve injury. To examine the effect of nerve injury on SGCs, we investigated the activation of SGCs after neuronal damage due to the extraction of the upper molars in rats. Three, 7, and 10 days after extraction, animals were fixed and the TG was removed. Cryosections of the ganglia were immunostained with antibodies against glial fibrillary acidic protein (GFAP), a marker of activated SGCs, and ATF3, a marker of damaged neurons. After tooth extraction, the number of ATF3-immunoreactive (IR) neurons enclosed by GFAP-IR SGCs had increased in a time-dependent manner in the maxillary nerve region of the TG. Although ATF3-IR neurons were not detected in the mandibular nerve region, the number of GFAP-IR SGCs increased in both the maxillary and mandibular nerve regions. Our results suggest that peripheral nerve injury affects the activation of TG neurons and the SGCs around the injured neurons. Moreover, our data suggest the existence of a neuronal interaction between maxillary and mandibular neurons via SGC activation

  20. Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally-charged images

    Directory of Open Access Journals (Sweden)

    RachaelBrown

    2012-10-01

    Full Text Available The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally-charged images from the International Affective Picture System. Skin sympathetic nerve activity was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively-charged images (erotica or negatively-charged images (mutilation were presented in blocks of fifteen images of a specific type, each block lasting two minutes. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction, however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively-charged and negatively-charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.

  1. Cavernous nerve reconstitution with the use of bone marrow stem cells and erectile function evaluation: an experimental animal study

    Directory of Open Access Journals (Sweden)

    Oskar Grau Kaufmann

    2009-12-01

    Full Text Available Objective: To assess the influence of adult stem cells from bone marrow of rats in the regeneration of cavernous nerve, taking the return of erectile function as a parameter in animals subjected to the apomorphine-induced test of erection. Methods: Forty-eight male Wistar-EPM rats, aged between nine and ten weeks, and weighing approximately 250 g were used. They were randomly divided into four study Groups containing 12 animals each, as follows: Group I: surgical exposure of the cavernous nerves bilaterally without injury; Group II: bilateral surgical injury of the cavernous nerve of approximately 3 mm, without reconstruction; Group III: bilateral surgical injury of the cavernous nerves of approximately 3 mm, and bilateral reconstruction with silicone guiding tubes containing saline solution inside; Group IV: bilateral surgical injury of the cavernous nerves of approximately 3 mm, and bilateral reconstruction with silicone guiding tubes filled with adult stem cells. Four weeks after surgery, the animals were injected with apomorphine for induction of erection. Rresults: In Group I there was complete erectile response in all animals (100% – 12 out of 12. On the other hand, none of the animals in Group II presented erection after the use of apomorphine. Five of the twelve animals of Group III (41.7% and nine of the 12 animals of Group IV (75% had erections after the stimulus. When we compared the frequency of restoration of erection in the four Groups, Group IV was shown to have a similar performance to Group I (p = 0.217, while Group III animals had a frequency of erections inferior to those in Group I (p = 0.005. Moreover, comparison of results of Groups III and IV versus Group II showed that the frequency of erections was statistically higher in the first two Groups (p = 0.037 and p < 0.001, respectively. Finally, Group IV presented a tendency to a larger number of erections when compared to Group III (75 versus 41.7% but this difference was not statistically significant (p = 0.098. Cconclusion: This study shows that adult stem cells from bone marrow, filling silicone guiding tubes, may promote the regeneration of cavernous nerves and restore erectile function in an animal model.

  2. Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity

    Science.gov (United States)

    Morimoto-Kobayashi, Yumie; Ohara, Kazuaki; Takahashi, Chika; Kitao, Sayoko; Wang, Guanying; Taniguchi, Yoshimasa; Katayama, Mikio; Nagai, Katsuya

    2015-01-01

    Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-?-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-?-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-?-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the ?-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or beverages to counteract the accumulation of body fat. PMID:26098641

  3. Very high frequency components of renal sympathetic nerve activity in conscious rats.

    Science.gov (United States)

    Chapuis, Bruno; Oréa, Valérie; Barrès, Christian; Julien, Claude

    2010-01-15

    The aim of this study was to examine whether multifibrenal sympathetic nerve activity (RSNA) of conscious rats contains frequency components of biological interest at frequencies above 25Hz. RSNA was recorded in 10 conscious Sprague-Dawley rats under baseline conditions and during infusion of vasoactive drugs that reflexly altered the mean RSNA level. The RSNA signal was band-pass filtered (300-3000Hz) before being sampled at 10,000Hz. The analytic envelope of this raw signal was then extracted using the Hilbert transform, and 132-s periods were submitted to Fourier transform analysis. Spectral power was computed from 0 to 25Hz and from 25 to 3000Hz (P(25-3000)). P(25-3000) was reduced by about 80% after either ganglionic blockade or euthanasia, which indicated that it was of biological origin and derived from the activity of postganglionic sympathetic neurons. After subtraction of post-mortem spectral power, basal P(25-3000) contributed 59.8+/-2.4% of total power. P(25-3000) was strongly barosensitive and thus, accounted for a major part of the reflex changes in total power. In each of the 10 rats, P(25-3000) was linearly correlated with the mean RSNA level (0.984+/-0.003) and even more so with the spectral power in the 0-25Hz frequency range (0.994+/-0.001). In conclusion, the RSNA of conscious rats contains very high frequency components that account for about 60% of the total spectral power and are modulated by the baroreceptor reflex. A reasonable approximation of this power can be obtained by computing spectra up to 25Hz. PMID:19783485

  4. Nerve growth factor eye drops improve visual acuity and electrofunctional activity in age-related macular degeneration: a case report

    Scientific Electronic Library Online (English)

    Alessandro, Lambiase; Marco, Coassin; Paola, Tirassa; Flavio, Mantelli; Luigi, Aloe.

    2009-12-01

    Full Text Available Age-related macular degeneration (ARMD) is a severe disease affecting visual function in the elderly. Currently available surgical and medical options do not guarantee a significant impact on the outcome of the disease. We describe the effects of nerve growth factor eye drop treatment in a 94 years [...] old female with ARMD, whose visual acuity was progressively worsening in spite of previous surgical and medical treatments. NGF eye drops improved visual acuity and electrofunctional parameters as early as 3 months after initiation of treatment. These results are in line with previous reports on a neuroprotective effect of NGF on retinal cells and on NGF eye drops bioavailability in the retina and optic nerve. No side effects were observed after five years of follow-up, suggesting that topical NGF treatment may be a safe and effective therapy for ARMD.

  5. Immobilization of cells via activated cell walls

    Energy Technology Data Exchange (ETDEWEB)

    Markt, M.; Kas, J.; Valentova, O.; Demnerova, K.; Vodrazka, Z.

    1986-10-01

    Cell walls of Saccharomyces cerevisiae and S. uvarum were activated by periodate oxidation of vicinal diol groups in cell wall polysaccharides. The aldehyde groups thus generated allow the yeast cells to be covalently bound to modified bead cellulose or macroporous glycidyl methacrylate supports, or to enzymes such as glucose oxidase and catalase. 6 references.

  6. Can local supply of bone marrow mononuclear cells improve the outcome from late tubular repair of human median and ulnar nerves?

    Science.gov (United States)

    Braga-Silva, J; Gehlen, D; Padoin, A V; Machado, D C; Garicochea, B; Costa da Costa, J

    2008-08-01

    The purpose of this non-randomised retrospective study was to compare nerve regeneration after reconnection with silicone tubes with two different strategies. A total of 44 patients with injured median or ulnar nerves in the forearm were surgically treated. In one group of patients, a silicone tube alone was placed in the nerve gap. In a second group, the silicone tube was filled with autologous bone marrow mononuclear cells obtained by aspiration from the iliac crest. Motor function, sensation and the effect of pain on function were assessed 1 year after surgery. The tubes filled with bone marrow cells showed better recovery than the empty tubes. The use of bone marrow mononuclear cells in addition to tube re-connection may promote better nerve regeneration than conventional tubular repair. PMID:18687837

  7. Optic nerve hypoplasia in children.

    OpenAIRE

    Zeki, S M; Dutton, G N

    1990-01-01

    Optic nerve hypoplasia (ONH) is characterised by a diminished number of optic nerve fibres in the optic nerve(s) and until recently was thought to be rare. It may be associated with a wide range of other congenital abnormalities. Its pathology, clinical features, and the conditions associated with it are reviewed. Neuroendocrine disorders should be actively sought in any infant or child with bilateral ONH. Early recognition of the disorder may in some cases be life saving.

  8. Active cheerleading with radial nerve palsy following supracondylar humerus fracture [Cheerleading mit Radialisparese nach suprakondylärer Humerusfraktur

    Directory of Open Access Journals (Sweden)

    Herold, Christian

    2013-10-01

    Full Text Available [english] Cheerleading is associated with substantial morbidity. As such, cheerleading fall-related injuries may cause serious to fatal outcomes especially falls from attempted pyramids. We report on a female adolescent cheerleader age 14 suffering a supracondylar humerus fracture related to a fall from a pyramid. Unfortunately, lateral pinning led to complete iatrogenic radial nerve palsy. However, given an intriguing compensatory athletic function of the wrist she was able to perform cheerleading artistic figures such as flic-flac within four months after the injury with a radial nerve palsy, which is highlighted in an attached video. 18 months after the radial palsy she was admitted to our hospital and underwent neuroma resection of the initially transsected radial nerve at the elbow and sural nerve grafting for radial nerve palsy.[german] Cheerleading kann zu verschiedensten Unfällen führen. Insbesondere bei dem Versuch Pyramiden zu bilden sind bereits Todesfälle aufgetreten. Wir berichten von einer 14-jährigen Cheerleaderin welche bei dem Versuch eine Pyramide zu bilden stürzte und sich eine suprakondyläre Humerusfraktur zuzog. Bei der osteosynthetischen Versorgung kam es leider zu einer kompletten Durchtrennung des N. radialis. Dennoch konnte sie bei der gegebenen erstaunlichen Kompensation ihrer Handgelenksgeweglichkeit weiterhin schwierige Cheerleading Übungen wie Flick-Flack durchführen, was im beigefügten Video verdeutlicht wird. 18 Monate nach Eintreten der Radialisparese wurde sie in unserer Klinik vorstellig und es wurde nach einer Neuromresektion eine Suralis Interposition zur Nervenrekonstruktion durchgeführt.

  9. Nerve growth factor rapidly induces c-fos mRNA in PC12 rat pheochromocytoma cells.

    OpenAIRE

    Milbrandt, J.

    1986-01-01

    The nerve growth factor (NGF)-mediated increase in c-fos gene expression in the rat pheochromocytoma PC12 cell line has been investigated. NGF treatment of PC12 cells results in an increased level of c-fos mRNA within 15 min. An approximately 100-fold increase in the level of c-fos mRNA occurs 30-45 min after exposure to NGF and the c-fos mRNA concentration returns to its basal level 2 hr after NGF treatment. Thus, the half-life of this RNA transcript is extremely short. In the presence of cy...

  10. Differentiated baroreflex modulation of sympathetic nerve activity during deep brain stimulation in humans.

    Science.gov (United States)

    Sverrisdóttir, Yrsa B; Green, Alexander L; Aziz, Tipu Z; Bahuri, Nor Faizal A; Hyam, Jonathan; Basnayake, Shanika D; Paterson, David J

    2014-05-01

    Targeted electric deep brain stimulation in midbrain nuclei in humans alters cardiovascular parameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at 2 distinct brain locations. The aim of this study was to evaluate sympathetic outflow in humans with deep brain stimulating electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Multiunit muscle sympathetic nerve activity was recorded in 17 patients undergoing deep brain stimulation for treatment of chronic neuropathic pain (n=7) and Parkinson disease (n=10). Sympathetic outflow was recorded during ON and OFF stimulation. Arterial blood pressure, heart rate, and respiratory frequency were monitored during the recording session, and spontaneous vasomotor and cardiac baroreflex sensitivity were assessed. Head-up tilt testing was performed separately in the patients with Parkinson disease postoperatively. Stimulation of the dorsal most part of the subthalamic nucleus and ventrolateral periaqueductal gray resulted in improved vasomotor baroreflex sensitivity, decreased burst frequency and blood pressure, unchanged burst amplitude distribution, and a reduced fall in blood pressure after tilt. Stimulation of the dorsolateral periaqueductal gray resulted in a shift in burst amplitude distribution toward larger amplitudes, decreased spontaneous beat-to-beat blood pressure variability, and unchanged burst frequency, baroreflex sensitivity, and blood pressure. Our results indicate that a differentiated regulation of sympathetic outflow occurs in the subthalamic nucleus and periaqueductal gray. These results may have implications in our understanding of abnormal sympathetic discharge in cardiovascular disease and provide an opportunity for therapeutic targeting. PMID:24516109

  11. Wilms’ Tumor Gene 1 (WT1) Silencing Inhibits Proliferation of Malignant Peripheral Nerve Sheath Tumor sNF96.2 Cell Line

    Science.gov (United States)

    Parenti, Rosalba; Cardile, Venera; Graziano, Adriana Carol Eleonora; Parenti, Carmela; Venuti, Assunta; Bertuccio, Maria Paola; Furno, Debora Lo; Magro, Gaetano

    2014-01-01

    Wilms’ tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. WT1 expression has been variably reported in both benign and malignant peripheral nerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of the present study was to characterize its potential pathogenetic role in these relatively uncommon malignant tumors. Firstly, immunohistochemical analyses in MPNST sNF96.2 cell line showed strong WT1 staining in nuclear and perinuclear areas of neoplastic cells. Thus, we investigated the effects of silencing WT1 by RNA interference. Through Western Blot analysis and proliferation assay we found that WT1 knockdown leads to the reduction of cell growth in a time- and dose-dependent manner. siWT1 inhibited proliferation of sNF96.2 cell lines likely by influencing cell cycle progression through a decrease in the protein levels of cyclin D1 and inhibition of Akt phosphorylation compared to the control cells. These results indicate that WT1 knockdown attenuates the biological behavior of MPNST cells by decreasing Akt activity, demonstrating that WT1 is involved in the development and progression of MPNSTs. Thus, WT1 is suggested to serve as a potential therapeutic target for MPNSTs. PMID:25474318

  12. Wilms' tumor gene 1 (WT1) silencing inhibits proliferation of malignant peripheral nerve sheath tumor sNF96.2 cell line.

    Science.gov (United States)

    Parenti, Rosalba; Cardile, Venera; Graziano, Adriana Carol Eleonora; Parenti, Carmela; Venuti, Assunta; Bertuccio, Maria Paola; Furno, Debora Lo; Magro, Gaetano

    2014-01-01

    Wilms' tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. WT1 expression has been variably reported in both benign and malignant peripheral nerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of the present study was to characterize its potential pathogenetic role in these relatively uncommon malignant tumors. Firstly, immunohistochemical analyses in MPNST sNF96.2 cell line showed strong WT1 staining in nuclear and perinuclear areas of neoplastic cells. Thus, we investigated the effects of silencing WT1 by RNA interference. Through Western Blot analysis and proliferation assay we found that WT1 knockdown leads to the reduction of cell growth in a time- and dose-dependent manner. siWT1 inhibited proliferation of sNF96.2 cell lines likely by influencing cell cycle progression through a decrease in the protein levels of cyclin D1 and inhibition of Akt phosphorylation compared to the control cells. These results indicate that WT1 knockdown attenuates the biological behavior of MPNST cells by decreasing Akt activity, demonstrating that WT1 is involved in the development and progression of MPNSTs. Thus, WT1 is suggested to serve as a potential therapeutic target for MPNSTs. PMID:25474318

  13. The neuromuscular activity of Bothriopsis bilineata smaragdina (forest viper) venom and its toxin Bbil-TX (Asp49 phospholipase A2) on isolated mouse nerve-muscle preparations.

    Science.gov (United States)

    Floriano, Rafael Stuani; Rocha, Thalita; Carregari, Victor Corasolla; Marangoni, Sergio; da Cruz-Höfling, Maria Alice; Hyslop, Stephen; Rodrigues-Simioni, Léa; Rowan, Edward G

    2015-03-01

    The presynaptic action of Bothriopsis bilineata smaragdina (forest viper) venom and Bbil-TX, an Asp49 PLA2 from this venom, was examined in detail in mouse phrenic nerve-muscle (PND) preparations in vitro and in a neuroblastoma cell line (SK-N-SH) in order to gain a better insight into the mechanism of action of the venom and associated Asp49 PLA2. In low Ca(2+) solution, venom (3?g/ml) caused a quadriphasic response in PND twitch height whilst at 10?g/ml the venom additionally induced an abrupt and marked initial contracture followed by neuromuscular facilitation, rhythmic oscillations of nerve-evoked twitches, alterations in baseline and progressive blockade. The venom slowed the relaxation phase of muscle twitches. In low Ca(2+), Bbil-TX [210nM (3?g/ml)] caused a progressive increase in PND twitch amplitude but no change in the decay time constant. Venom (10?g/ml) and Bbil-TX (210nM) caused minor changes in the compound action potential (CAP) amplitude recorded from sciatic nerve preparations, with no significant effect on rise time and latency; tetrodotoxin (3.1nM) blocked the CAP at the end of the experiments. In mouse triangularis sterni nerve-muscle (TSn-m) preparations, venom (10?g/ml) and Bbil-TX (210nM) significantly reduced the perineural waveform associated with the outward K(+) current while the amplitude of the inward Na(+) current was not significantly affected. Bbil-TX (210nM) caused a progressive increase in the quantal content of TSn-m preparations maintained in low Ca(2+) solution. Venom (3?g/ml) and toxin (210nM) increased the calcium fluorescence in SK-N-SH neuroblastoma cells loaded with Fluo3 AM and maintained in low or normal Ca(2+) solution. In normal Ca(2+), the increase in fluorescence amplitude was accompanied by irregular and frequent calcium transients. In TSn-m preparations loaded with Fluo4 AM, venom (10?g/ml) caused an immediate increase in intracellular Ca(2+) followed by oscillations in fluorescence and muscle contracture; Bbil-TX did not change the calcium fluorescence in TSn-m preparations. Immunohistochemical analysis of toxin-treated PND preparations revealed labeling of junctional ACh receptors but a loss of the presynaptic proteins synaptophysin and SNAP25. Together, these data confirm the presynaptic action of Bbil-TX and show that it involves modulation of K(+) channel activity and presynaptic protein expression. PMID:25572337

  14. Myelinating cocultures of rat retinal ganglion cell reaggregates and optic nerve oligodendrocyte precursor cells.

    Science.gov (United States)

    Watkins, Trent A; Scholze, Anja R

    2014-10-01

    This protocol describes the generation of a rapidly myelinating central nervous system coculture for the study of complex neuronal-glial interactions in vitro. Postnatal rat retinal ganglion cells (RGCs) purified by immunopanning are promoted to cluster into reaggregates and then allowed to extend dense beds of radial axons for 10-14 d. Subsequently, rodent oligodendrocyte precursor cells are purified by immunopanning, transfected if desired, and seeded on top of the RGC reaggregates. Under the conditions described here, compact myelin can be observed within 6 d. PMID:25275100

  15. Apoptosis of sensory neurons and satellite cells after sciatic nerve transection in C57BL/6J mice

    Scientific Electronic Library Online (English)

    A.L.R., Oliveira.

    2001-03-01

    Full Text Available The rate of axonal regeneration, after sciatic nerve lesion in adult C57BL/6J mice, is reduced when compared to other isogenic strains. It was observed that such low regeneration was not due just to a delay, since neuronal death was observed. Two general mechanisms of cell death, apoptosis and necro [...] sis, may be involved. By using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique, we demonstrated that a large number of sensory neurons, as well as satellite cells found in the dorsal root ganglia, were intensely labeled, thus indicating that apoptotic mechanisms were involved in the death process. Although almost no labeled neurons or satellite cells were observed one week after transection, a more than ten-fold increase in TUNEL labeling was detected after two weeks. The results obtained with the C57BL/6J strain were compared with those of the A/J strain, which has a much higher peripheral nerve regeneration potential. In A/J mice, almost no labeling of sensory neurons or satellite cells was observed after one or two weeks, indicating the absence of neuronal loss. Our data confirm previous observations that approximately 40% of C57BL/6J sensory neurons die after sciatic nerve transection, and indicate that apoptotic events are involved. Also, our observations reinforce the hypothesis that the low rate of axonal regeneration occurring in C57BL/6J mice may be the result of a mismatch in the timing of the neurons need for neurotrophic substances, and production of the latter by non-neuronal cells in the distal stump.

  16. Apoptosis of sensory neurons and satellite cells after sciatic nerve transection in C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Oliveira A.L.R.

    2001-01-01

    Full Text Available The rate of axonal regeneration, after sciatic nerve lesion in adult C57BL/6J mice, is reduced when compared to other isogenic strains. It was observed that such low regeneration was not due just to a delay, since neuronal death was observed. Two general mechanisms of cell death, apoptosis and necrosis, may be involved. By using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL technique, we demonstrated that a large number of sensory neurons, as well as satellite cells found in the dorsal root ganglia, were intensely labeled, thus indicating that apoptotic mechanisms were involved in the death process. Although almost no labeled neurons or satellite cells were observed one week after transection, a more than ten-fold increase in TUNEL labeling was detected after two weeks. The results obtained with the C57BL/6J strain were compared with those of the A/J strain, which has a much higher peripheral nerve regeneration potential. In A/J mice, almost no labeling of sensory neurons or satellite cells was observed after one or two weeks, indicating the absence of neuronal loss. Our data confirm previous observations that approximately 40% of C57BL/6J sensory neurons die after sciatic nerve transection, and indicate that apoptotic events are involved. Also, our observations reinforce the hypothesis that the low rate of axonal regeneration occurring in C57BL/6J mice may be the result of a mismatch in the timing of the neurons need for neurotrophic substances, and production of the latter by non-neuronal cells in the distal stump.

  17. Effect of exercise-induced activation of sympathetic nerve activity on clearance of 123I-MIBG from the myocardium

    International Nuclear Information System (INIS)

    The effect of exercise on the cardiac kinetics of 123I-MIBG was investigated in the present study. 123I-MIBG was administered intravenously at rest in 6 healthy male volunteers, and anterior planar and SPECT images were obtained 15 minutes, and 2 and 4 hours after administration (protocol A). After 4 weeks, 123I-MIBG was again administered intravenously at rest, and images were obtained 15 minutes later. After imaging, the subjects ran 10 km in approximately 1 hour, and anterior planar and SPECT images were obtained 2 and 4 hours after administration of 123I-MIBG (protocol B). The heart-to-mediastinum uptake ratio (H/M) was calculated from each anterior planar image, and the mean 123I-MIBG clearance from 15 minutes to 2 hours, and from 2 hours to 4 hours was calculated with a bull's eye display. The H/M was much lower after exercise. The mean clearance rate between 15 minutes and 2 hours in protocol B was significantly higher than that between 2 hours and 4 hours, and that between 15 minutes and 2 hours in protocol A. It was concluded that the clearance rate of 123I-MIBG may be a useful index of cardiac sympathetic nerve activity. (author)

  18. Effect of exercise-induced activation of sympathetic nerve activity on clearance of 123I-MIBG from the myocardium.

    Science.gov (United States)

    Sugihara, H; Shiga, K; Terada, K; Kinoshita, N; Taniguchi, Y; Ito, K; Adachi, Y; Ushijima, Y; Nakagawa, M; Maeda, T

    1998-08-01

    The effect of exercise on the cardiac kinetics of 123I-MIBG was investigated in the present study. 123I-MIBG was administered intravenously at rest in 6 healthy male volunteers, and anterior planar and SPECT images were obtained 15 minutes, and 2 and 4 hours after administration (protocol A). After 4 weeks, 123I-MIBG was again administered intravenously at rest, and images were obtained 15 minutes later. After imaging, the subjects ran 10 km in approximately 1 hour, and anterior planar and SPECT images were obtained 2 and 4 hours after administration of 123I-MIBG (protocol B). The heart-to-mediastinum uptake ratio (H/M) was calculated from each anterior planar image, and the mean 123I-MIBG clearance from 15 minutes to 2 hours, and from 2 hours to 4 hours was calculated with a bull's eye display. The H/M was much lower after exercise. The mean clearance rate between 15 minutes and 2 hours in protocol B was significantly higher than that between 2 hours and 4 hours, and that between 15 minutes and 2 hours in protocol A. It was concluded that the clearance rate of 123I-MIBG may be a useful index of cardiac sympathetic nerve activity. PMID:9795701

  19. Multitarget Dielectrophoresis Activated Cell Sorter

    OpenAIRE

    Kim, Unyoung; Qian, Jiangrong; Kenrick, Sophia A.; Daugherty, Patrick S.; Soh, H. Tom

    2008-01-01

    The ability to rapidly and efficiently isolate specific viruses, bacteria, or mammalian cells from complex mixtures lies at the heart of biomedical applications ranging from in vitro diagnostics to cell transplantation therapies. Unfortunately, many current selection methods for cell separation, such as magnetic activated cell sorting (MACS), only allow the binary separation of target cells that have been labeled via a single parameter (e.g., magnetization). This limitation makes it challengi...

  20. Sciatic nerve injury induces apoptosis of dorsal root ganglion satellite glial cells and selectively modifies neurosteroidogenesis in sensory neurons.

    Science.gov (United States)

    Schaeffer, Véronique; Meyer, Laurence; Patte-Mensah, Christine; Eckert, Anne; Mensah-Nyagan, Ayikoe G

    2010-01-15

    Neurosteroids are synthesized either by glial cells, by neurons, or within the context of neuron-glia cross-talk. Various studies suggested neurosteroid involvement in the control of neurodegeneration but there is no evidence showing that the natural protection of nerve cells against apoptosis directly depends on their own capacity to produce neuroprotective neurosteroids. Here, we investigated the interactions between neurosteroidogenesis and apoptosis occurring in sensory structures of rats subjected to neuropathic pain generated by sciatic nerve chronic constriction injury (CCI). Using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), we observed no apoptotic cells in the spinal cord up to 30 days after CCI although pain symptoms such as mechano-allodynia, thermal and mechanical hyperalgesia were evidenced with the Hargreaves's behavioral and von Frey filament tests. In contrast, double-labeling experiments combining TUNEL and immunostaining with antibodies against glutamine synthetase or neuronal nuclei protein revealed apoptosis occurrence in satellite glial cells (SGC) (not in neurons) of CCI rat ipsilateral dorsal root ganglia (DRG) at day 30 after injury. Pulse-chase experiments coupled with high performance liquid chromatography and flow scintillation detection showed that, among numerous biosynthetic pathways converting [(3)H]pregnenolone into various [(3)H]neurosteroids, only [(3)H]estradiol formation was selectively modified and upregulated in DRG of CCI rats. Consistently, immunohistochemical investigations localized aromatase (estradiol-synthesizing enzyme) in DRG neurons but not in SGC. Pharmacological inhibition of aromatase caused apoptosis of CCI rat DRG neurons. Altogether, our results suggest that endogenously produced neurosteroids such as estradiol may be pivotal for the protection of DRG sensory neurons against sciatic nerve CCI-induced apoptosis. PMID:19565659

  1. SIRT1 Activating Compounds Reduce Oxidative Stress and Prevent Cell Death in Neuronal Cells

    Directory of Open Access Journals (Sweden)

    KennethSShindler

    2012-12-01

    Full Text Available Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators reduce oxidative stress and promote mitochondrial function in neuronal cells. Oxidative stress, marked by reactive oxygen species (ROS accumulation, was induced in RGC-5 cells by serum deprivation, or addition of doxorubicin or hydrogen peroxide, and resulted in significant cell loss. SIRT1 activators resveratrol and SRTAW04 reduced ROS levels, and promoted cell survival in RGC-5 cells as well as primary RGC cultures. Effects were blocked by SIRT1 siRNA. SIRT1 activators also increased expression of succinate dehydrogenase, a mitochondrial enzyme, and promoted deacetylation of PGC-1?, a co-enzyme involved in mitochondrial function. Results show SIRT1 activators prevent cell loss by reducing oxidative stress and promoting mitochondrial function in a neuronal cell line. Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress.

  2. Role of tumor necrosis factor receptor-1 in the death of retinal ganglion cells following optic nerve crush injury in mice.

    Science.gov (United States)

    Tezel, Gülgün; Yang, Xiangjun; Yang, Junjie; Wax, Martin B

    2004-01-23

    To assess the specific role of tumor necrosis factor (TNF) death receptor signaling in the induction of retinal ganglion cell (RGC) death, optic nerves of mice deficient for TNF receptor-1 (TNF-R1-/-) and control mice (C57BL/6J) were unilaterally subjected to crush injury. Counts of RGCs and their axons 6 weeks after the injury demonstrated that their loss was significantly less in TNF-R1-/- mice compared to controls. The most prominent decrease in neuronal loss detected in TNF-R1-/- mice was beyond the initial 2-week period after the injury. This time period was correlated with the period of glial activation and increased glial immunolabeling for TNF-alpha in these eyes. No further protection against neuronal loss was detectable in TNF-R1-/- mice treated with D-JNKI1, a specific inhibitor of c-Jun N-terminal protein kinase (JNK). However, anti-JNK treatment of control animals provided a significant protection against neuronal loss during the same secondary degeneration period. Phospho-JNK immunolabeling of RGCs in control mice subjected to optic nerve crush significantly decreased following their treatment with D-JNKI1, and anti-JNK treatment protected RGCs from degeneration in these animals, similar to the lack of TNF-R1. These findings provide evidence that TNF death receptor signaling is involved in the secondary degeneration of RGCs following optic nerve injury, and is associated with JNK signaling. Since secondarily degenerating neurons are viable targets for neuroprotection, inhibition of TNF death receptor signaling may be an effective strategy to protect RGCs in several neurodegenerative injuries. PMID:14697498

  3. Activation of codependent transcription factors is required for transcriptional induction of the vgf gene by nerve growth factor and Ras.

    OpenAIRE

    D'Arcangelo, G; Habas, R; Wang, S; Halegoua, S; Salton, S R

    1996-01-01

    Nerve growth factor (NGF) treatment of PC12 cells leads to the elaboration of a neuronal phenotype, including the induction of neuronally expressed genes such as vgf. To study vgf transcription, we have created chimeric vgf/beta-globin genes in which vgf promoter sequences drive the expression of the beta-globin reporter gene or of a chimeric beta-globin gene fused to 3' untranslated vgf gene sequences. We have found that the level of inducibility of the latter construct by NGF resembles that...

  4. Effect of nerve growth factor on the synthesis of amino acids in PC12 cells

    International Nuclear Information System (INIS)

    Radioactive short-chain fatty acids preferentially label glutamine relative to glutamate in brain due to compartmentation of glutamine and glutamate. To determine whether this phenomenon occurs in a single cell culture model, we examined the effect of fatty acid chain length on the synthesis as well as pool size of selected amino acids in rat pheochromocytoma PC12 cells, a cell culture model of the large glutamate compartment in neurons. Intracellular 14C-amino acids were quantitated by HPLC, and the incorporation of [U-14C]-glucose, [1-14C]-butyrate, [1-14C]-octanoate, and [1-14C]-palmitate into five amino acids was measured in native and NGF-treated PC12 cells. NGF pretreatment decreased the intracellular concentration of amino acids as did addition of fatty acids but these effects were not additive. Specific activities of amino acids in native cells labelled by 14C-octanoate were 1,300 DPM/nmol, 490 DPM/nmol, 200 DPM/nmol, and 110 DPM/nmol for glutamate, aspartate, glutamine, and serine, respectively. No radioactivity was detected in alanine. Similar specific activities were noted when 14C-butyrate was the precursor; however, there was at least 5-fold less if 14C-palmitate was the precursor. Pretreatment of cells with NGF decreased the specific activity of amino acids by 25-65%. Specific activities of amino acids synthesized from 14C-glucose decreased in the following order: glutamate, 1,640 DPM/nmol; aspartate, 1,210 DPM/nmol; alanine, 580 DPM/nmol; glutamine, 275mol; alanine, 580 DPM/nmol; glutamine, 275 DPM/nmol; and serine, 80 DPM/nmol for native cells. NGF pretreatment decreased the specific activities of glutamate and glutamine, but not of the other 3 amino acids. The preferred precursor for glutamate synthesis in native PC12 cells was glucose followed by octanoate, butyrate and palmitate (16:6:3:1)

  5. ATP Release through Lysosomal Exocytosis from Peripheral Nerves: The Effect of Lysosomal Exocytosis on Peripheral Nerve Degeneration and Regeneration after Nerve Injury

    OpenAIRE

    Jung, Junyang; Jo, Hyun Woo; Kwon, Hyunseob; Jeong, Na Young

    2014-01-01

    Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adeno...

  6. Prejunctional modulatory action of neuropeptide Y on responses due to antidromic activation of peripheral terminals of capsaicin-sensitive sensory nerves in the isolated guinea-pig ileum.

    OpenAIRE

    Takaki, M.; Nakayama, S.

    1991-01-01

    1. The effect of neuropeptide Y (NPY) on motor responses produced by activation of capsaicin-sensitive primary afferents in the guinea-pig isolated ileum was determined by use of capsaicin itself and electrical mesenteric nerve stimulation as stimuli. 2. NPY inhibited or suppressed the cholinergic contractile response produced by electrical mesenteric nerve stimulation while leaving the contractile response to a threshold concentration of capsaicin. 3. NPY had no effect on motor responses pro...

  7. Characterization of the MRC OX40 antigen of activated CD4 positive T lymphocytes--a molecule related to nerve growth factor receptor.

    Science.gov (United States)

    Mallett, S; Fossum, S; Barclay, A N

    1990-01-01

    The antigen recognized by the monoclonal antibody (mAb) MRC OX40 is present on activated rat CD4 positive T lymphocytes but not other cells. cDNA clones were isolated from an expression library using the MRC OX40 mAb and the protein sequence for the OX40 antigen deduced. It contains a typical signal sequence and a single putative transmembrane sequence of 25 predominantly hydrophobic amino acids giving an extracellular domain of 191 amino acids and a cytoplasmic domain of 36 amino acids. The sequence of the extracellular domain includes a cysteine-rich region with sequence similarities with the low affinity nerve growth factor receptor (NGFR) of neurons and the CD40 antigen present on human B cells. Within this region three cysteine-rich motifs can be recognized in OX40 compared with four similar motifs in both NGFR and CD40. OX40, CD40 and NGFR constitute a new superfamily of molecules with expression including lymphoid cells (OX40, CD40) and neuronal cells (NGFR). This is reminiscent of the immunoglobulin superfamily whose molecules are variously found at the surface of lymphoid or brain cells or both. Images Fig. 1. PMID:2157591

  8. The effects of dietary treatment with essential fatty acids on sciatic nerve conduction and activity of the Na+/K+ pump in streptozotocin-diabetic rats.

    Science.gov (United States)

    Lockett, M J; Tomlinson, D R

    1992-02-01

    1. This study examined the effects of dietary essential fatty acid supplementation (5% (w/w) evening primrose oil) upon sciatic motor nerve conduction velocity and 86Rb+ pumping in sciatic nerve endoneurial preparations in rats with 4 to 5 weeks of streptozotocin-induced diabetes. 2. Control diabetic rats (dietary supplementation with 5% (w/w) hydrogenated coconut oil) exhibited a reduction in motor nerve conduction velocity (16%; P less than 0.05) compared to similarly-fed non-diabetic controls, but there was no significant alteration in ouabain-sensitive 86Rb+ pumping, a parameter reflecting activity of the Na+/K+ pump. 3. Treatment of diabetic rats with evening primrose oil prevented completely the development of the motor nerve conduction velocity deficit without affecting the severity of diabetes. Evening primrose oil treatment did not significantly affect motor nerve conduction velocity of non-diabetic animals. 4. Evening primrose oil treatment caused a significant reduction in activity of the Na+/K+ pump in sciatic nerves of diabetic animals (45%; P less than 0.05). 5. These results suggest that the acute conduction velocity defect arising in streptozotocin-diabetic rats, and the actions of evening primrose oil upon this, are independent of any effect on activity of the Na+/K+ pump. Other putative mechanisms are discussed. PMID:1313726

  9. GLP-1 signals via ERK in peripheral nerve and prevents nerve dysfunction in diabetic mice

    DEFF Research Database (Denmark)

    Jolivalt, CG; Fineman, M

    2011-01-01

    Aim: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that induces glucose-dependent insulin secretion and may have neurotrophic properties. Our aim was to identify the presence and activity of GLP-1 receptors (GLP-1Rs) in peripheral nerve and to assess the impact of GLP-1R agonists on diabetes-induced nerve disorders. Methods: Tissues were collected from streptozotocin-diabetic rats. GLP-1R function was assessed by incubating tissues from normal and diabetic rats with GLP-1R agonists and antagonists and measuring induction of ERK1/2 phosphorylation by Western blot. Streptozotocin-diabetic mice were also treated with the GLP-1R agonist exenatide for 8 weeks to assess the impact of GLP-1R signalling on peripheral nerve function and structure. Results: GLP-1R protein was detected in rat dorsal root ganglia and the neurons and Schwann cells of the sciatic nerve. Protein levels were not affected by streptozotocin-induced diabetes. GLP-1R agonists did not signal via ERK1/2 in sciatic nerve of normal rats. However, GLP-1R agonists significantly increased pERK1/2 levels in sciatic nerves from diabetic rats, indicating that GLP-1Rs are functional in this tissue. Exenatide treatment did not affect blood sugar, insulin levels or paw thermal response latencies in either control or diabetic mice. However, the reductions of motor nerve conduction velocity and paw intraepidermal fibre density seen in diabetic mice were attenuated by exenatide treatment. Conclusions: These data show that the peripheral nerve of diabetic rodents exhibits functional GLP-1R and suggest that GLP-1R-mediated ERK-signalling in sciatic nerve of diabetic rodents may protect large motor fibre function and small C fibre structure by a mechanism independent of glycaemic control.

  10. Casein kinase II regulates N-methyl-D-aspartate receptor activity in spinal cords and pain hypersensitivity induced by nerve injury.

    Science.gov (United States)

    Chen, Shao-Rui; Zhou, Hong-Yi; Byun, Hee Sun; Chen, Hong; Pan, Hui-Lin

    2014-08-01

    Increased N-methyl-d-aspartate receptor (NMDAR) activity and phosphorylation in the spinal cord are critically involved in the synaptic plasticity and central sensitization associated with neuropathic pain. However, the mechanisms underlying increased NMDAR activity in neuropathic pain conditions remain poorly understood. Here we show that peripheral nerve injury induces a large GluN2A-mediated increase in NMDAR activity in spinal lamina II, but not lamina I, neurons. However, NMDAR currents in spinal dorsal horn neurons are not significantly altered in rat models of diabetic neuropathic pain and resiniferatoxin-induced painful neuropathy (postherpedic neuralgia). Inhibition of protein tyrosine kinases or protein kinase C has little effect on NMDAR currents potentiated by nerve injury. Strikingly, casein kinase II (CK2) inhibitors normalize increased NMDAR currents of dorsal horn neurons in nerve-injured rats. In addition, inhibition of calcineurin, but not protein phosphatase 1/2A, augments NMDAR currents only in control rats. CK2 inhibition blocks the increase in spinal NMDAR activity by the calcineurin inhibitor in control rats. Furthermore, nerve injury significantly increases CK2? and CK2? protein levels in the spinal cord. In addition, inhibition of CK2 or CK2? knockdown at the spinal level substantially reverses pain hypersensitivity induced by nerve injury. Our study indicates that neuropathic pain conditions with different etiologies do not share the same mechanisms, and increased spinal NMDAR activity is distinctly associated with traumatic nerve injury. CK2 plays a prominent role in the potentiation of NMDAR activity in the spinal dorsal horn and may represent a new target for treatments of chronic pain caused by nerve injury. PMID:24898266

  11. INCREASED CARDIAC SYMPATHETIC NERVE ACTIVITY IN HEART FAILURE IS NOT DUE TO DESENSITIZATION OF THE ARTERIAL BAROREFLEX

    OpenAIRE

    Watson, A. M. D.; Hood, S. G.; Ramchandra, R.; Mcallen, R. M.; May, C. N.

    2007-01-01

    Increased sympathetic drive to the heart worsens prognosis in heart failure, but the level of cardiac sympathetic nerve activity (CSNA) has been assessed only by indirect methods, which do not permit testing whether its control by arterial baroreceptors is defective. To do this, CSNA was measured directly in 16 female sheep, 8 of which had been ventricularly paced at 200–220 beats/min for 4–6 weeks, until their ejection fraction fell to between 35 and 40%. Recording electrodes were surgic...

  12. Endocrine cells and nerve ganglia of the small intestine of the Opossum Didelphis aurita Wied-Neuwied, 1826 (Mammalia: Didelphidae)

    Scientific Electronic Library Online (English)

    Gláucia M., Freitas-Ribeiro; Cláudio C., Fonseca; Sirlene S.R., Sartori; Alan, Loures-Ribeiro; Clóvis A., Neves.

    2012-09-01

    Full Text Available Os sistemas nervoso e endócrino controlam integra-damente os movimentos intestinais, a secreção de suas glândulas e também participam dos processos de digestão e absorção de nutrientes. Portanto, o objetivo central deste estudo foi verificar a existência de uma possível relação entre o número de cél [...] ulas nervosas e gânglios dos plexos submucosos e mioentéricos e o número de células endócrinas no intestino delgado de adultos de D. aurita. As técnicas de coloração utilizadas foram Grimelius, Masson-Fontana modificada, imunoperoxidase direta e H-E. As células endócrinas argirófilas, argentafins e imunorreativas à insulina não variaram numericamente entre as regiões inicial, média e final do duodeno, jejuno e íleo (P>0,05), exceto as células argirófilas no jejuno (P Abstract in english The nervous and endocrine systems jointly control intestinal movements, secretions of their glands and also participate of the processes of nutrient digestion and absorption. Therefore, the central objective of this study was to verify the existence of a possible relationship between the number of n [...] ervous cells and ganglia of the submucosal and myenteric plexuses and the number of endocrine cells in the small intestine of adult D. aurita. The utilized staining techniques were Grimelius, modified Masson-Fontana, direct immunoperoxidase and H-E. Argyrophillic, argentaffin and insulin immunoreactive endocrine cells do not numerically vary between the initial, mid and final regions of the duodenum, jejunum and ileum (P>0.05), except for argyrophillic cells in the jejunum (P>0.05). No numerical relationship has yet been verified between the number of nerve ganglia and endocrine cells, and also between nervous and endocrine cells. We recommended the use of new immunohistochemical techniques to confirm the numerical correlation between the nervous and endocrine systems in the small intestine. The morphology and distribution of endocrine cells and the nerve ganglia studied were similar to those encountered in eutherian mammals.

  13. Radiosensitivity of glial progenitor cells of the perinatal and adult rat optic nerve studied by an in vitro clonogenic assay

    Energy Technology Data Exchange (ETDEWEB)

    Maazen, R.W.M. van der; Verhagen, I.; Kleiboer, B.J.; Kogel, A.J. van der (Nijmegen University (Netherlands). Institute of Radiotherapy)

    1991-04-01

    The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligo-dendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro systems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS. (author). 28 refs.; 4 figs.; 1 tab.

  14. Radiosensitivity of glial progenitor cells of the perinatal and adult rat optic nerve studied by an in vitro clonogenic assay

    International Nuclear Information System (INIS)

    The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligo-dendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro systems to have a great potential in unravelstems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS. (author). 28 refs.; 4 figs.; 1 tab

  15. Combination of engineered neural cell adhesion molecules and GDF-5 for improved neurite extension in nerve guide concepts.

    Science.gov (United States)

    Niere, Marc; Braun, Bettina; Gass, Rea; Sturany, Sabine; Volkmer, Hansjürgen

    2006-06-01

    Current therapeutical approaches for the treatment of severe lesions in the peripheral nervous system rely on the use of autologous tissue or the body's own Schwann cells. However, these approaches are limited and alternative strategies for peripheral nerve regeneration are required. Here we evaluate combinations of a variety of neuronal regeneration factors including engineered cell adhesion molecules and growth factors in embryonic model neurons to test the possible improvement of artificial nerve guides by cooperative mechanisms. Cell adhesion molecules L1 and neurofascin synergistically promote neurite elongation. The outgrowth promoting properties of both proteins can be combined and further increased within one chimeric protein. Addition of growth and differentiation factor 5 (GDF-5) further enhances neurite outgrowth in a substrate-independent manner. This effect is not due to a protective mode of action of GDF-5 against pro-apoptotic stimuli. Consequently, the study supports the idea that different modes of action of pro-regenerative factors may contribute synergistically to neurite outgrowth and emphasizes the applicability of combinations of proteins specifically involved in development of the nervous system for therapeutical approaches. PMID:16497371

  16. Neuromuscular activity of Bothrops neuwiedi pauloensis snake venom in mouse nerve-muscle preparations

    Scientific Electronic Library Online (English)

    A. M., Durigon; C. R., Borja-Oliveira; C. A., Dal Belo; Y., Oshima-Franco; J. C., Cogo; A. J., Lapa; C., Souccar; L., Rodrigues-Simioni.

    2005-03-01

    Full Text Available The pharmacological effects of Bothrops neuwiedi pauloensis venom on mouse phrenic nerve-diaphragm (PND) preparations were studied. Venom (20 mug/ml) irreversibly inhibited indirectly evoked twitches in PND preparations (60 ± 10% inhibition, mean ± SEM; p[...] indirectly and directly (curarized preparations) evoked twitches in mouse hemidiaphragms. In the absence of Ca2+, venom (50 mug/ml), produced partial blockade only after an 80 min incubation, which reached 40.3 ± 7.8% (p

  17. The effects of functional magnetic nanotubes with incorporated nerve growth factor in neuronal differentiation of PC12 cells

    International Nuclear Information System (INIS)

    In this in vitro study the efficiency of magnetic nanotubes to bind with nerve growth factor (NGF) and the ability of NGF-incorporated magnetic nanotubes to release the bound NGF are investigated using rat pheochromocytoma cells (PC12 cells). It is found that functional magnetic nanotubes with NGF incorporation enabled the differentiation of PC12 cells into neurons exhibiting growth cones and neurite outgrowth. Microscope observations show that filopodia extending from neuron growth cones were in close proximity to the NGF-incorporated magnetic nanotubes, at times appearing to extend towards or into them. These results show that magnetic nanotubes can be used as a delivery vehicle for NGF and thus may be exploited in attempts to treat neurodegenerative disorders such as Parkinson's disease with neurotrophins. Further neurite outgrowth can be controlled by manipulating magnetic nanotubes with external magnetic fields, thus helping in directed regeneration

  18. Age-related yield of adipose-derived stem cells bearing the low-affinity nerve growth factor receptor.

    Science.gov (United States)

    Cuevas-Diaz Duran, Raquel; González-Garza, Maria Teresa; Cardenas-Lopez, Alejandro; Chavez-Castilla, Luis; Cruz-Vega, Delia Elva; Moreno-Cuevas, Jorge E

    2013-01-01

    Adipose-derived stem cells (ADSCs) are a heterogeneous cell population that may be enriched by positive selection with antibodies against the low-affinity nerve growth factor receptor (LNGFR or CD271), yielding a selective cell universe with higher proliferation and differentiation potential. This paper addresses the need for determining the quantity of ADSCs positive for the CD271 receptor and its correlation with donor's age. Mononuclear cells were harvested from the lower backs of 35 female donors and purified using magnetic beads. Multipotency capacity was tested by the expression of stemness genes and through differentiation into preosteoblasts and adipocytes. A significant statistical difference was found in CD271(+) concentrations between defined age intervals. The highest yield was found within women on the 30-40-year-old age range. CD271(+) ADSCs from all age groups showed differentiation capabilities as well as expression of typical multipotent stem cell genes. Our data suggest that the amount of CD271(+) cells correlates inversely with age. However, the ability to obtain these cells was maintained through all age ranges with a yield higher than what has been reported from bone marrow. Our findings propose CD271(+) ADSCs as the primary choice for tissue regeneration and autologous stem cell therapies in older subjects. PMID:24376462

  19. Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images

    Science.gov (United States)

    Brown, Rachael; James, Cheree; Henderson, Luke A.; Macefield, Vaughan G.

    2012-01-01

    The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing. PMID:23060818

  20. Ammodytoxin, a neurotoxic secreted phospholipase A2, can act in the cytosol of the nerve cell

    International Nuclear Information System (INIS)

    Recent identification of intracellular proteins that bind ammodytoxin (calmodulin, 14-3-3 proteins, and R25) suggests that this snake venom presynaptically active phospholipase A2 acts intracellularly. As these ammodytoxin acceptors are cytosolic and mitochondrial proteins, the toxin should be able to enter the cytosol of a target cell and remain stable there to interact with them. Using laser scanning confocal microscopy we show here that Alexa-labelled ammodytoxin entered the cytoplasm of the rat hippocampal neuron and subsequently also its nucleus. The transport of proteins into the nucleus proceeds via the cytosol of a cell, therefore, ammodytoxin passed the cytosol of the neuron on its way to the nucleus. Although it is not yet clear how ammodytoxin is translocated into the cytosol of the neuron, our results demonstrate that its stability in the cytosol is not in question, providing the evidence that the toxin can act in this cellular compartment

  1. MicroRNA-210 promotes proliferation and invasion of peripheral nerve sheath tumor cells targeting EFNA3.

    Science.gov (United States)

    Wang, Zhengguang; Yin, Bangliang; Wang, Bing; Ma, Zemin; Liu, Weidong; Lv, Guohua

    2013-01-01

    MicroRNA (miR) plays an important role in tumorigenesis including malignant peripheral nerve sheath tumor (MPNST). miR-210 downregulation is frequently observed in a variety of tumors. In this study, miR-210 was identified as downregulated in MPNST cells, and its potential target ephrin-A3 (EFNA3) was upregulated in them compared with neurofibroma cells using quantitative real-time (qRT)-PCR. Luciferase reporter assay further demonstrates that EFNA3 is a target of miR-210. Then it is confirmed that miR-210 can regulate EFNA3 mRNA and protein expression in MPNST ST88-14 (NF1 wild-type) and sNF96.2 (NF1 mutant type) cell lines. The functions of miR-210 in MPNST cells were investigated, and the results showed that overexpression of miR-210 increased cellular viability, colony formation, S phase percentage, and invasiveness of MPNST cells. Inversely, inhibition of miR-210 expression induced suppression of proliferation and invasion of MPNST cells. These results suggest that miR-210-mediated EFNA3 promotion of proliferation and invasion of MPNST cells plays an important role in MPNST tumorigenesis and progression. miR-210 and EFNA3 may be candidate novel therapeutic targets for MPNST. PMID:24512729

  2. Decreased Nerve Conduction Velocity in Football Players

    Directory of Open Access Journals (Sweden)

    Daryoush Didehdar

    2014-06-01

    Full Text Available Background: Lower limbs nerves are exposed to mechanical injuries in the football players and the purpose of this study is to evaluate the influence of football on the lower leg nerves. Materials and Methods: Nerve conduction studies were done on 35 male college students (20 football players, 15 non active during 2006 to 2007 in the Shiraz rehabilitation faculty. Standard nerve conduction techniques using to evaluate dominant and non dominant lower limb nerves. Results: The motor latency of deep peroneal and tibial nerves of dominant leg of football players and sensory latency of superficial peroneal, tibial and compound nerve action potential of tibial nerve of both leg in football players were significantly prolonged (p<0.05. Motor and sensory nerve conduction velocity of tibial and common peroneal in football players were significant delayed (p<0.05. Conclusion: It is concluded that football is sport with high contact and it causes sub-clinical neuropathies due to nerve entrapment.

  3. Nasal-Type Extranodal Natural Killer/T-cell Neurolymphomatosis Confined to the Lumbar Nerve Roots: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Chun; Mun, Sung Hee; Lee, Young Hwan [Catholic University, Daegu (Korea, Republic of)

    2009-11-15

    Neurolymphomatosis refers to lymphoma that has infiltrated the peripheral nervous system and this is the least common clinical presentation of nervous system lymphoma. Most neurolymphomatosis is due to B-cell non-Hodgkin lymphoma, and most patients show lymphomatous infiltration in the meninges and brain parenchyma, in addition to peripheral nervous system involvement. We diagnosed a case of neurolymphomatosis that was confined to the right 4th and 5th lumbar nerve roots without involvement of the meninges or brain parenchyma in a patient with the nasal-type extranodal natural killer/T-cell lymphoma. We made this diagnosis based on the MRI and 18F-FDG PET-CT findings and the clinical manifestations.

  4. Nasal-Type Extranodal Natural Killer/T-cell Neurolymphomatosis Confined to the Lumbar Nerve Roots: A Case Report

    International Nuclear Information System (INIS)

    Neurolymphomatosis refers to lymphoma that has infiltrated the peripheral nervous system and this is the least common clinical presentation of nervous system lymphoma. Most neurolymphomatosis is due to B-cell non-Hodgkin lymphoma, and most patients show lymphomatous infiltration in the meninges and brain parenchyma, in addition to peripheral nervous system involvement. We diagnosed a case of neurolymphomatosis that was confined to the right 4th and 5th lumbar nerve roots without involvement of the meninges or brain parenchyma in a patient with the nasal-type extranodal natural killer/T-cell lymphoma. We made this diagnosis based on the MRI and 18F-FDG PET-CT findings and the clinical manifestations

  5. Expression of P30, a protein with adhesive properties, in Schwann cells and neurons of the developing and regenerating peripheral nerve

    Science.gov (United States)

    1991-01-01

    P30 is a heparin-binding protein with adhesive and neurite outgrowth- promoting properties present at high levels in the developing rat central nervous system (Rauvala, H., and R. Pihlaskari. 1987 J. Biol. Chem. 262:16625-16635). Partial sequencing of p30 has revealed homology or identity with HMG-1 (Rauvala, H., J. Merenmies, R. Pihlaskari, M. Korkolainen, M.-L. Huhtala, and P. Panula. 1988. J. Cell Biol. 107:2292- 2305), a 28-kD protein that was originally purified from the thymus (Goodwin, G.H., C. Sanders, and E. W. Johns. 1973. Eur. J. Biochem. 38:14-19) which binds DNA in vitro. We have analyzed the distribution of p30 in the developing rat peripheral nervous system (PNS). P30 was detected by immunohistochemistry and Western blot analysis using antibodies raised against intact p30 and against a synthetic peptide corresponding to the amino terminus of the p30 molecule. P30 was localized to nonnuclear compartments of neurons and peripheral glial cells (Schwann cells). P30 immunoreactivity of PNS neurons persisted into adulthood. In contrast, Schwann cell staining decreased after the second postnatal week and was not detectable in adult animals. Neuron- Schwann cell contact was correlated with diminished p30 levels in Schwann cells. Schwann cells of the normal adult sciatic nerve did not express p30; however, when deprived of axonal contact by nerve transection, the Schwann cells of the distal nerve stained intensely for p30. In addition, when Schwann cells and dorsal root ganglion neurons were grown in coculture, Schwann cells that were associated with neurites were not as intensely stained by anti-p30 as Schwann cells that were not in contact with neurons. The pattern of p30 expression during development and regeneration, and its apparent regulation by cell-cell contact suggests that p30 plays a role in the interaction between neurons and Schwann cells during morphogenesis of peripheral nerves. PMID:1999471

  6. Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer

    DEFF Research Database (Denmark)

    Fjord-Larsen, L; Kusk, Poul Henrik

    2012-01-01

    Nerve growth factor (NGF) is a potential therapeutic agent for Alzheimer's disease (AD) as it has positive effects on the basal forebrain cholinergic neurons whose degeneration correlates with the cognitive decline in AD. We have previously described an encapsulated cell biodelivery device, NsG0202, capable of local delivery of NGF by a genetically modified human cell line, NGC-0295. The NsG0202 devices have shown promising safety and therapeutic results in a small phase 1b clinical study. However, results also show that the NGF dose could advantageously be increased. We have used the sleeping beauty transposon expression technology to establish a new clinical grade cell line, NGC0211, with at least 10 times higher NGF production than that of NGC-0295. To test whether encapsulation of this cell line provides a relevant dose escalation step in delivering NGF for treatment of the cognitive decline in AD patients, we have validated the bioactivity of devices with NGC0211 and NGC-0295 cells in normal rat striatumas well as in the quinolinic acid striatal lesion model. These preclinical animal studies show that implantation of devices with NGC0211 cells lead to significantly higher NGF output, which in both cases correlate with highly improved potency.Gene Therapy advance online publication, 24 November 2011; doi:10.1038/gt.2011.178.

  7. Influence of Transplantation of Bone Mesenchymal Stem Cells on the Acute Injury Motor Function of the Spinal Cord and Expression of the Nerve Growth Factor of the Rat

    Directory of Open Access Journals (Sweden)

    Zhen Li

    2013-01-01

    Full Text Available Purpose to research the therapeutic affect of the allograft of Bones Mesenchymal Stem Cells (BMSCs on the acute injury of the spinal nerve of the rat. Method: Take 1 Westar healthy rat, collect the bone marrow, adopt the adherence method to separate BMSCs and culture and mark them, cultivate the BMSCs culture solution with the cell population of about 5H104 ?L-1 for transplantation. Establish 40 westar rat models with the acute injury of the spinal cord, which shall be divided as the transplantation group and the control group, 20 pieces for each group. After a week of injury, inject BMSCs slowly to the injury center of the rat's spinal cord, inject the physiological saline to the control group and observe and inspect the rehabilitation efficacy of the hind limb function and the protein expression of the Nerve Growth Factor (NGF and Brain-derived Neurotrophic Factor (BDNF of the rats of two groups. Result: The rehabilitation efficacy of the hind limb function of the transplantation group is obvious better than that of the control group after 3-8 weeks of injury and the difference is of significance (p<0.05. Kill two groups of rats after 8 weeks and it is found that the transplantation group is obviously higher than the control group through inspection of the protein expression of NGF and BDNF. The difference is of significance (p<0.05. Conclusion the allograft of BMSCs can remarkably improve the rehabilitation of the lower limb motor function of the rats with acute injury of the spinal nerve, which is possibly related with that the transplantation of BMSCs can promote the regeneration and repair of the rat's spinal nerves. It is proven through the NGF and BDNF protein expression data from the experiment of the transplantation group and the control group that BMSCs transplantation can improve the expression of some NGF of the rats with spinal nerve injury. These nerve factors are beneficial for regeneration, growth and repair of the injured nerve tissue cells, so as to further confirm that the rehabilitation of the lower limb motor function of the rat's with acute injury of the spinal nerve thanks to the induced regeneration, growth and repair of the spinal nerve cells by BMSCs transplantation.

  8. Jugular venous overflow of noradrenaline from the brain: a neurochemical indicator of cerebrovascular sympathetic nerve activity in humans

    DEFF Research Database (Denmark)

    Mitchell, D.A.; Lambert, G.

    2009-01-01

    A novel neurochemical method was applied for studying the activity of sympathetic nerves in the human cerebral vascular system. The aim was to investigate whether noradrenaline plasma kinetic measurements made with internal jugular venous sampling reflect cerebrovascular sympathetic activity. A database was assembled of fifty-six healthy subjects in whom total body noradrenaline spillover (indicative of whole body sympathetic nervous activity), brain noradrenaline spillover and brain lipophlic noradrenaline metabolite (3,4-dihydroxyphenolglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG)) overflow rates were measured. These measurements were also made following ganglion blockade (trimethaphan, n = 6), central sympathetic inhibition (clonidine, n = 4) and neuronal noradrenaline uptake blockade (desipramine, n = 13) and in a group of patients (n = 9) with pure autonomic failure (PAF). The mean brain noradrenline spillover and brain noradrenaline metabolite overflow in healthy subjects were 12.5 +/- 1.8, and 186.4 +/- 25 ng min(-1), respectively, with unilateral jugular venous sampling for both. Total body noradrenaline spillover was 605.8 ng min(-1) +/- 34.4 ng min(-1). As expected, trimethaphan infusion lowered brain noradrenaline spillover (P = 0.03), but perhaps surprisingly increased jugular overflow of brain metabolites (P = 0.01). Suppression of sympathetic nervous outflow with clonidine lowered brain noradrenaline spillover (P = 0.004), without changing brain metabolite overflow (P = 0.3). Neuronal noradrenaline uptake block with desipramine lowered the transcranial plasma extraction of tritiated noradrenaline (P = 0.001). The PAF patients had 77% lower brain noradrenaline spillover than healthy recruits (P = 0.06), indicating that in them sympathetic nerve degeneration extended to the cerebral circulation, but metabolites overflow was similar to healthy subjects (P = 0.3). The invariable discordance between noradrenline spillover and noradrenaline metabolite overflow from the brain under these different circumstances indicates that the two measures arise from different sources, i.e. noradrenaline spillover originates from the cerebral vasculature outside the blood-brain barrier, and the noradrenaline metabolites originate primarily from brain noradrenergic neurons. We suggest that measurements of transcranial plasma noradrenaline spillover have utility as a method for assessing the sympathetic nerve activity of the cerebral vasculature Udgivelsesdato: 2009/6/1

  9. Nerve in reversal reaction.

    Science.gov (United States)

    Job, C K

    1996-01-01

    1. Much of the nerve destruction in leprosy takes place during the reactive phase, both during ENL reaction and RR. 2. The high risk patients expected to develop RR are borderline patients with generalized lesions (more than 10 skin lesions) and those presenting with three or more thickened nerve trunks. 3. In RR there is a sudden enhancement of already existing DTH to M. leprae and its antigens resulting in the release of excessive quantities of TNF alpha, INF gamma, and IL-2. The triggering mechanisms of this phenomenon is poorly understood. 4. The already existing granulomas suddenly increase considerably in size due to oedema and rapid influx of lymphocytes, Langhan's and foreign body giant cells. Fragments of M. leprae are also present in the granuloma of some patients. 5. In RR, the acute granulomatous inflammation can produce destruction of nerves even to the extent of causing caseous necrosis of the nerve tissue and irreversible paralysis. The swelling of the nerves due to sudden increase in inflammatory cells and oedema within an unyielding perineurium produce ischaemia and transient paralysis. 6. With prompt administration of anti-inflammatory drugs, paralysis recovers quickly, if it is of ischaemic origin; but will not recover if the Schwann cells and other nerve tissues are destroyed as a result of the immune granuloma. 7. A course of corticosteroids for six months along with anti-leprosy therapy is suggested in high risk patients as a preventive measure. 8. Further the serious problem of continuing nerve damage after clinical cure should be urgently tackled. PMID:8727113

  10. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2011-05-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  11. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2012-02-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  12. Optic nerve aspergillosis.

    Science.gov (United States)

    Yuan, Lisi; Prayson, Richard A

    2015-07-01

    We report a 55-year-old woman with optic nerve Aspergillosis. Aspergillus is an ubiquitous airborne saprophytic fungus. Inhaled Aspergillus conidia are normally eliminated in the immunocompetent host by innate immune mechanisms; however, in immunosuppressed patients, they can cause disease. The woman had a past medical history of hypertension and migraines. She presented 1year prior to death with a new onset headache behind the left eye and later developed blurred vision and scotoma. A left temporal artery biopsy was negative for giant cell arteritis. One month prior to the current admission, she had an MRI showing optic nerve thickening with no other findings. Because of the visual loss and a positive antinuclear antibody test, she was given a trial of high dose steroids and while it significantly improved her headache, her vision did not improve. At autopsy, the left optic nerve at the level of the cavernous sinus and extending into the optic chiasm was enlarged in diameter and there was a 1.3cm firm nodule surrounding the left optic nerve. Histologically, an abscess surrounded and involved the left optic nerve. Acute angle branching, angioinvasive fungal hyphae were identified on Grocott's methenamine silver stained sections, consistent with Aspergillus spp. No gross or microscopic evidence of systemic vasculitis or infection was identified in the body. The literature on optic nerve Aspergillosis is reviewed. PMID:25861888

  13. Protein Phosphatase Magnesium Dependent 1A (PPM1A) Plays a Role in the Differentiation and Survival Processes of Nerve Cells

    OpenAIRE

    Shohat, Meytal; Ben-meir, Daniella; Lavi, Sara

    2012-01-01

    The serine/threonine phosphatase type 2C (PPM1A) has a broad range of substrates, and its role in regulating stress response is well established. We have investigated the involvement of PPM1A in the survival and differentiation processes of PC6-3 cells, a subclone of the PC12 cell line. This cell line can differentiate into neuron like cells upon exposure to nerve growth factor (NGF). Overexpression of PPM1A in naive PC6-3 cells caused cell cycle arrest at the G2/M phase followed by apoptosis...

  14. Internalization of intracerebrally administered porcine galanin (1-29) by a discrete nerve cell population in the hippocampus of the rat.

    Science.gov (United States)

    Jansson, A; Tinner, B; Andbjer, B; Razani, H; Wang, F; Schött, P A; Agnati, L F; Ogren, S O; Fuxe, K

    2000-01-01

    In spite of numerous studies utilizing intraventricular administration of porcine galanin (1-29), little is known about the spread and cellular distribution of exogenous galanin following intraventricular administration. In this study a discrete nerve cell body population with their dendrites became strongly galanin immunoreactive (IR) in the dorsal hippocampus following intraventricular porcine galanin (1.5 nmol/rat). Time course experiments showed that after time intervals of 10 and 20 min, but not at 60 min, scattered small- to medium-sized galanin-IR nerve cell bodies and their dendrites were present in all layers of the dorsal and ventral hippocampus. In double-immunolabeling experiments most of these nerve cells were identified as putative GABA interneurons costoring NPY-IR or somatostatin-IR in some cases. Twenty minutes after intraventricular injection of artificial cerebrospinal fluid (aCSF), only endogenous punctate and coarse galanin-IR terminals were found, but no galanin-IR cell bodies. Intrahippocampal injection of fluorophore-labeled galanin resulted in the appearance of fluorescent nerve cell bodies with the same morphology and localization as in the above experiments. Coadministration of the putative galanin antagonist M35 (0.5 nmol) and galanin (1.5 nmol) resulted in a reduced number of galanin-IR nerve cell bodies in the hippocampus of half of the rats. These findings support the existence of a population of putative hippocampal GABA interneurons with the ability to internalize and concentrate galanin and/or its fragments present in the extracellular fluid, possibly mediated by galanin receptors. PMID:10683281

  15. TRPM8 on mucosal sensory nerves regulates colitogenic responses by innate immune cells via CGRP.

    Science.gov (United States)

    de Jong, P R; Takahashi, N; Peiris, M; Bertin, S; Lee, J; Gareau, M G; Paniagua, A; Harris, A R; Herdman, D S; Corr, M; Blackshaw, L A; Raz, E

    2015-05-01

    TRPM8 is the molecular sensor for cold; however, the physiological role of TRPM8+ neurons at mucosal surfaces is unclear. Here we evaluated the distribution and peptidergic properties of TRPM8+ fibers in naive and inflamed colons, as well as their role in mucosal inflammation. We found that Trpm8(-/-) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis, and that Trpm8(-/-) CD11c+ DCs (dendritic cells) showed hyperinflammatory responses to toll-like receptor (TLR) stimulation. This was phenocopied in calcitonin gene-related peptide (CGRP) receptor-deficient mice, but not in substance P receptor-deficient mice, suggesting a functional link between TRPM8 and CGRP. The DSS phenotype of CGRP receptor-deficient mice could be adoptively transferred to wild-type (WT) mice, suggesting that CGRP suppresses the colitogenic activity of bone marrow-derived cells. TRPM8+ mucosal fibers expressed CGRP in human and mouse colon. Furthermore, neuronal CGRP contents were increased in colons from naive and DSS-treated Trpm8(-/-) mice, suggesting deficient CGRP release in the absence of TRPM8 triggering. Finally, treatment of Trpm8(-/-) mice with CGRP reversed their hyperinflammatory phenotype. These results suggest that TRPM8 signaling in mucosal sensory neurons is indispensable for the regulation of innate inflammatory responses via the neuropeptide CGRP. PMID:25269705

  16. Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

    International Nuclear Information System (INIS)

    The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Forty patients with CHF [left ventricular ejection fraction (LVEF) 123I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. After treatment, in patients receiving perindopril, TDS decreased from 39±10 to 34±9 (P123I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF. (orig.)

  17. Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients.

    Science.gov (United States)

    Groehs, Raphaela V; Toschi-Dias, Edgar; Antunes-Correa, Ligia M; Trevizan, Patrícia F; Rondon, Maria Urbana P B; Oliveira, Patrícia; Alves, Maria J N N; Almeida, Dirceu R; Middlekauff, Holly R; Negrão, Carlos E

    2015-05-01

    Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ? 40%, peak V?o2 ? 20 ml·kg(-1)·min(-1) were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients. PMID:25747752

  18. Chronic upregulation of activated microglia immunoreactive for galectin-3/Mac-2 and nerve growth factor following diffuse axonal injury

    Directory of Open Access Journals (Sweden)

    Chrzaszcz MaryAnn

    2010-05-01

    Full Text Available Abstract Background Diffuse axonal injury in patients with traumatic brain injury (TBI can be associated with morbidity ranging from cognitive difficulties to coma. Magnetic resonance imaging scans now allow early detection of axonal injury following TBI, and have linked cognitive disability in these patients to white matter signal changes. However, little is known about the pathophysiology of this white matter injury, and the role of microglial activation in this process. It is increasingly recognized that microglia constitute a heterogeneous population with diverse roles following injury. In the present studies, we tested the hypothesis that following diffuse axonal injury involving the corpus callosum, there is upregulation of a subpopulation of microglia that express the lectin galectin-3/Mac-2 and are involved in myelin phagocytosis. Methods Adult mice were subject to midline closed skull injury or sham operation and were sacrificed 1, 8, 14 or 28 days later. Immunohistochemistry and immunofluorescence techniques were used to analyze patterns of labelling within the corpus callosum qualitatively and quantitatively. Results Activated microglia immunoreactive for galectin-3/Mac-2 were most abundant 1 day following injury. Their levels were attenuated at later time points after TBI but still were significantly elevated compared to sham animals. Furthermore, the majority of galectin-3/Mac-2+ microglia were immunoreactive for nerve growth factor in both sham and injured animals. Conclusions Our results suggest that galectin-3/Mac-2+ microglia play an important role in the pathogenesis of diffuse axonal injury both acutely and chronically and that they mediate their effects, at least in part by releasing nerve growth factor.

  19. Expression of JUN, KROX, and CREB transcription factors in goldfish and rat retinal ganglion cells following optic nerve lesion is related to axonal sprouting

    OpenAIRE

    Herdegen, Thomas; Bastmeyer, Martin; Ba?hr, Mathias; Stu?rmer, Claudia; Bravo, Rodrigo; Zimmermann, Manfred

    1993-01-01

    Goldfish and rat optic nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and upto 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After optic nerve cut ...

  20. Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain

    DEFF Research Database (Denmark)

    Fjord-Larsen, L; Kusk, P

    2010-01-01

    Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device, capable of local delivery of NGF. The clinical device, named NsG0202, houses an NGF-secreting cell line (NGC-0295), which is derived from a human retinal pigment epithelial (RPE) cell line, stably genetically modified to secrete NGF. Bioactivity and correct processing of NGF was confirmed in vitro. NsG0202 devices were implanted in the basal forebrain of Göttingen minipigs and the function and retrievability were evaluated after 7 weeks, 6 and 12 months. All devices were implanted and retrieved without associated complications. They were physically intact and contained a high number of viable and NGF-producing NGC-0295 cells after explantation. Increased NGF levels were detected in tissue surrounding the devices. The implants were well tolerated as determined by histopathological brain tissue analysis, blood analysis, and general health status of the pigs. The NsG0202 device represents a promising approach for treating the cognitive decline in AD patients.

  1. mTOR and its downstream pathway are activated in the dorsal root ganglion and spinal cord after peripheral inflammation, but not after nerve injury

    OpenAIRE

    Liang, Lingli; Tao, Bo; Fan, Longchang; Yaster, Myron; zhang, yi.; Tao, Yuan-Xiang

    2013-01-01

    Protein translation controlled through activation of mammalian target of rapamycin (mTOR) participates in many physiological and pathological processes. However, whether such activation is required for chronic pain is still unknown. Here, we examined activation of the mTOR signaling pathway during complete Freund's adjuvant (CFA)-induced chronic inflammatory pain and L5 spinal nerve ligation (SNL)-induced neuropathic pain in rats. Western blot analysis showed significantly increased levels of...

  2. Patterned substrates and methods for nerve regeneration

    Science.gov (United States)

    Mallapragada, Surya K.; Heath, Carole; Shanks, Howard; Miller, Cheryl A.; Jeftinija, Srdija

    2004-01-13

    Micropatterned substrates and methods for fabrication of artificial nerve regeneration conduits and methods for regenerating nerves are provided. Guidance compounds or cells are seeded in grooves formed on the patterned substrate. The substrates may also be provided with electrodes to provide electrical guidance cues to the regenerating nerve. The micropatterned substrates give physical, chemical, cellular and/or electrical guidance cues to promote nerve regeneration at the cellular level.

  3. Optic Nerve Drusen

    Science.gov (United States)

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Drusen En Español Read in Chinese What are optic nerve drusen? Optic nerve drusen are abnormal globular ...

  4. Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

    OpenAIRE

    Salton, S R; Fischberg, D J; Dong, K W

    1991-01-01

    Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nuclei...

  5. Anesthetic induction agents, sympathetic nerve activity and baroreflex sensitivity: a study in rabbits comparing thiopental, propofol and etomidate.

    Directory of Open Access Journals (Sweden)

    Aono H

    2001-08-01

    Full Text Available The mechanisms of arterial hypotension following intravenous anesthetic induction agents are multifactorial. The purpose of this study was to evaluate and compare the effects of thiopental, propofol and etomidate on hemodynamics, sympathetic outflow and arterial baroreflex sensitivity using not only neuraxis-intact but also totally baro-denervated rabbits. A total of 60 rabbits was anesthetized with urethane, tracheotomized, and mechanically ventilated with oxygen in nitrogen (FiO2 0.5. The left renal sympathetic nerve was isolated and placed on a bipolar electrode to record renal sympathetic nerve activity (RSNA. Thirty animals underwent a surgical preparation of total baroreceptor denervation. Bolus injections of an anesthesia induction dose of thiopental 4 mg/kg and twice the induction dose of propofol 4 mg/kg significantly decreased RSNA to the same extent (19.4+/-6.7 and 19.7+/-5.2% reduction, mean +/- SEM and mean arterial pressure (MAP also to the same extent (19.5+/-4.6 and 22.1+/-3.1% reduction in the neuraxis-intact animals. RSNA was increased (34.5+/-6% without reduction of MAP by an induction dose of etomidate, 0.3 mg/kg. Sympathetic barosensitivity was attenuated even 10 min after thiopental at 4 mg/kg or propofol at 4 mg/kg (68% and 54% of control, respectively. Propofol at 2 mg/kg (induction dose and etomidate at 0.6 mg/kg decreased RSNA and MAP only in the baro-denervated animals. It was found from the barosensitivity study that patients can be hemodynamically unstable even though blood pressure has returned to normal after thiopental and propofol administration. Data suggest that etomidate can even stimulate the sympathetic nervous system and increase sympathetic outflow. It was also clearly found from the baro-denervated animal study that thiopental was stronger than propofol in directly suppressing sympathetic outflow at the induction dose.

  6. Immunolocalization of tight junction proteins, occludin and ZO-1, and glucose transporter GLUT1 in the cells of the blood-nerve barrier.

    Science.gov (United States)

    Tserentsoodol, N; Shin, B C; Koyama, H; Suzuki, T; Takata, K

    1999-12-01

    Facilitated-diffusion glucose transporter GLUT1 is abundant in the blood-nerve barrier. To observe the relationship between glucose transfer across the barrier and the molecular architecture of the barrier, we examined the localization of GLUT1 and tight junction proteins, occludin and zonula occludens-1 (ZO-1), by immunofluorescence microscopy and immunogold electron microscopy in the rat sciatic nerve. GLUT1 was enriched at the whole aspects of the plasma membranes of the cells of the barrier: perineurial cells, and endothelial cells of the blood vessels in the endoneurium. These GLUT1-positive cells were also positive for occludin and ZO-1, both of which were localized at tight junctions. ZO-1 additionally was present in the GLUT1-negative cells not serving as the blood-nerve barrier. These observations suggest that occludin in the tight junctions and GLUT1 at the plasma membranes in the cells of the barrier may constitute a mechanism for the selective transfer of glucose across the barrier while preventing the non-specific flow of blood constituents. PMID:10678575

  7. Minocycline is cytoprotective in human trabecular meshwork cells and optic nerve head astrocytes by increasing expression of XIAP, survivin, and Bcl-2

    Directory of Open Access Journals (Sweden)

    Marcus Kernt

    2010-06-01

    Full Text Available Marcus Kernt, Aljoscha S Neubauer, Kirsten H Eibl, Armin Wolf, Michael W Ulbig, Anselm Kampik, Cristoph HirneissDepartment of Ophthalmology, Ludwig-Maximilians-University, Munich, GermanyIntroduction: Primary open-angle glaucoma (POAG is one of the leading causes of blindness. Activation of optic nerve head astrocytes (ONHA and loss of trabecular meshwork cells (TMC are pathognomonic for this neurodegenerative disease. Oxidative stress and elevated levels of transforming growth factor beta (TGF? play an important role in the pathogenesis of POAG. This study investigates the possible antiapoptotic and cytoprotective effects of minocycline on TMC and ONHA under oxidative stress and increased TGF? levels.Methods: TMC and ONHA were treated with minocycline 1–150 ?M. Possible toxic effects and IC50 were evaluated after 48 hours. Cell proliferation and viability were examined in order to assess the protective effects of minocycline on TMC and ONHA. Expression of Bcl-2, XIAP, and survivin, as well as their mRNA expression, were assessed by real time polymerase chain reaction (RT-PCR and Western Blot analysis 48 hours after treatment with minocycline alone and additional incubation with TGF?-2 or oxidative stress.Results: Minocycline 1–75 ?M showed no toxic effects on TMC and ONHA. Under conditions of oxidative stress, both TMC and ONHA showed an increase in viability and an ability to proliferate when treated with minocycline 20–40 ?M. RT-PCR and Western blotting yielded an overexpression of Bcl-2, XIAP, and survivin when TMC or ONHA were treated with minocycline 20–40 ?M under conditions of oxidative stress and when additionally incubated with TGF?-2.Conclusion: Minocycline up to 75 ?M does not have toxic effects on TMC and ONHA. Treatment with minocycline 20–40 ?M led to increased viability and proliferation under oxidative stress and TGF?-2, as well as overexpression of Bcl-2, XIAP, and survivin. This protective pathway may help to prevent apoptotic cell death of TMC and ONHA and therefore be a promising approach to avoidance of progression of glaucomatous degeneration.Keywords: glaucoma, apoptosis, minocycline, trabecular meshwork, optic nerve head astrocytes

  8. Immunohistochemistry of GluR1 subunits of AMPA receptors of rat cerebellar nerve cells

    Scientific Electronic Library Online (English)

    Orlando J., Castejón; Michael E., Dailey.

    2009-08-01

    Full Text Available The localization of GluR1 subunits of ionotropic glutamate receptors in the glial cells and inhibitory neurons of cerebellar cortex and their association with the climbing and parallel fibers, and basket cell axons were studied. Samples of P14 and P21 rat cerebellar cortex were exposed to a specific [...] antibody against GluR1 subunit(s) of AMPA receptors and were examined with confocal laser scanning microscopy. GluR1 strong immunoreactivity was confined to Purkinje cell and the molecular layer. Weak GluR1 immunoreactivity was observed surrounding some Golgi cells in the granule cell layer. Intense GluR1 immunoreactivity was localized around Purkinje, basket, and stellate cells. Purkinje cells expressed strong GluR1 immunoreactivity surrounding the cell body, primary dendritic trunk and secondary and tertiary spiny dendritic branches. Marked immunofluorescent staining was also detected in the Bergmann glial fibers at the level of middle and outer third molecular layer. Positive immunofluorescence staining was also observed surrounding basket and stellate cells, and in the capillary wall. These findings suggest the specific localization of GluR1 subunits of AMPA receptors in Bergmann glial cells, inhibitory cerebellar neurons, and the associated excitatory glutamatergic circuits formed by climbing and parallel fibers, and by the inhibitory basket cell axons.

  9. Intra-articular injections of hyaluronan solutions of different elastoviscosity reduce nociceptive nerve activity in a model of osteoarthritic knee joint of the guinea pig

    OpenAIRE

    Gomis, Ana; Miralles, Ana; Schmidt, Robert Franz; Belmonte, Carlos

    2009-01-01

    Objective: To study in guinea pigs knee joints the effects of intra-articular injection of HYADD®4-G (Fidia-Farmaceutici), a novel hyaluronan (HA)-derived elastoviscous material and of Hyalgan® (Fidia-Farmaceutici), a HA product with very low viscoelasticity, on movement-evoked nociceptor impulse activity from normal and inflamed knee joints. Design: Nociceptor impulse activity was recorded from single A? and C fibers of the medial articular nerve either under control conditions or after indu...

  10. Optic Nerve Atrophy

    Science.gov (United States)

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Atrophy En Español Read in Chinese What is the optic nerve? The optic nerve contains over one million nerves ...

  11. The enhancement of growth and differentiation of rat adrenal nerve cells by the addition of conditioned medium from human fibroblast cultures

    OpenAIRE

    Hong, Jong Soo; Kim, Dae Suk; Kim, Seon Hee; Choi, Duk Ho; Lee, Jin Ha; Lee, Hyeon Yong

    1998-01-01

    The growth of rat adrenal nerve cells was remarkably enhanced by supplementing the cultured medium from the human fibroblast cell line, Hs 68. Maximum specific growth rate and length of the neurites were observed as 0.076 (1/hr) and 0.026 mm, respectively in 20% supplement of five day old medium. In adding more than 20% of the cultured medium both cell and neurite growth was severely decreased. It was interesting that the cultured medium from Hs 68 cells could play a role in the extension of ...

  12. Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

    OpenAIRE

    Hantaï, D; Rao, J. S.; Festoff, B. W.

    1990-01-01

    Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen. These results suggest that neural regulation of muscle extracellular matrix metabolism accompanies or precedes regeneration after injury and is mediated by activation of PAs. I...

  13. Nerve Blocks

    Science.gov (United States)

    ... as the sciatic nerve, your doctor will tell you to speak up if you get a sudden jolt of pain. This means ... covered by insurance and the possible charges that you will incur. Web ... from the American College of Radiology (ACR) and the Radiological Society ...

  14. [Mast cell-derived exosome participates in acupoint-stimulation initiated local network activities].

    Science.gov (United States)

    Chen, Bo; Li, Ming-yue; Guo, Yi; Zhao, Xue; Liu, Yang-yang

    2015-02-01

    The exosome, released from mast cells, T cells, B cells and many other types of cells, is the common form of vesicle transportation between cells and participates in the exchange of information between cells, and may be also involved in acupuncture induced clinical effects. In the present paper, the authors reviewed recent development of researches on this field from 1) acupuncture stimulation induces changes of number and function of mast cells in the local acupoint area, probably being the key factor for initiating acupuncture effect; 2) acupuncture stimulation induces release of neurotransmitters, hormones, cytokines, Ca2+, etc., in the local acupoint region, possibly being closely associated with the production of clinical effects; 3) acupuncture stimulation results in excitation of sensory afferent nerve fibers, triggering neuro-regulation; 4) exosomes derived from mast cells contain multiple neurotransmitters, hormones, cytokines, etc. to activate immune cells and sensory afferent fibers, inducing immuno-regulation and neuro-regulation; and 5) acupuncture stimulation induced release of Ca2+, ATP, etc. may potentiate release and transportation of exosomes. However, current researches are lack of excavation of network connection and transformation from basic research to clinical application. The authors hold that the exosome, released from mast cells by needling acupoints, acts as a messenger in network connection of nerve-mast cell-signal molecule in the body and may be one of the key factors of therapeutic effects. PMID:25845227

  15. Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity

    Directory of Open Access Journals (Sweden)

    Schaller Peter

    2006-03-01

    Full Text Available Abstract Background Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV. It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs followed by a shorter inspiratory time (Sindelar et al, J Appl Physiol, 2005 [Epub ahead of print]. Changes in lung mechanics, as observed in preterm infants with respiratory distress syndrome and after surfactant treatment, might therefore influence the inspiratory activity when applying PAV early after surfactant treatment. Objective To investigate the regulation of breathing and ventilatory response in surfactant-depleted young cats during PAV and during continuous positive airway pressure (CPAP early after surfactant instillation in relation to phrenic nerve activity (PNA and the activity of PSRs. Methods Seven anesthetized, endotracheally intubated young cats were exposed to periods of CPAP and PAV with the same end-expiratory pressure (0.2–0.5 kPa before and after lung lavage and after surfactant instillation. PAV was set to compensate for 75% of the lung elastic recoil. Results Tidal volume and respiratory rate were higher with lower PaCO2 and higher PaO2 during PAV than during CPAP both before and after surfactant instillation (p Conclusion PSR activity and the control of breathing are maintained during PAV in surfactant-depleted cats early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP.

  16. Evaluation of the changes in the muscle sympathetic nerve activity and anterior tibial muscle blood flow caused by the Valsalva maneuver in patients with lumbago and healthy subjects.

    Science.gov (United States)

    Nambu, Akihiko; Aoki, Takafumi; Shirai, Yasumasa; Ito, Hiromoto

    2005-04-01

    Clinical symptoms affecting the lower extremities are common among lumber spinal disorder patients. Pain, numbness and sensory disturbance are major signs of these symptoms, and have been suggested to be related to sympathetic nerve disturbance. This study was designed to examine whether these patients experience a difference in sympathetic nerve flow in terms of muscle sympathetic nerve activity (MSA) compared to healthy subjects. Five patients with lumbar intervertebral disc herniation of the spine (LIDH) and four patients with lumbar spinal canal stenosis (LSCS) were examined along with six healthy volunteers. Basic MSAs for IDH and SCS patients that were introduced from a common peroneal nerve were found to be statistically higher than those of the control subjects. MSA behavior and muscle blood flow introduced from the tibialis anterior muscle over 30 seconds while performing the Valsalva maneuver, a well-known technique used to artificially facilitate MSA, were examined for all subjects, and showed relatively slower changes for LIDH and LSCS patients compared to the normal subjects. Muscle blood flow was inversely proportional to MSA for the normal subjects, and this relationship was observed for IDH patients as well as SCS patients. However, MSA and the muscle blood flow of patients gradually changed while performing the Valsalva maneuver relative to the control subjects. This suggests that the systemic physiological response to the maneuver is maintained, but that, some local modification mechanisms exist. PMID:15940017

  17. Signaling pathways mediating a selective induction of nitric oxide synthase II by tumor necrosis factor alpha in nerve growth factor-responsive cells

    Directory of Open Access Journals (Sweden)

    Saragovi H Uri

    2005-09-01

    Full Text Available Abstract Background Inflammation and oxidative stress play a critical role in neurodegeneration associated with acute and chronic insults of the nervous system. Notably, affected neurons are often responsive to and dependent on trophic factors such as nerve growth factor (NGF. We previously showed in NGF-responsive PC12 cells that tumor necrosis factor alpha (TNF? and NGF synergistically induce the expression of the free-radical producing enzyme inducible nitric oxide synthase (iNOS. We proposed that NGF-responsive neurons might be selectively exposed to iNOS-mediated oxidative damage as a consequence of elevated TNF? levels. With the aim of identifying possible therapeutic targets, in the present study we investigated the signaling pathways involved in NGF/TNF?-promoted iNOS induction. Methods Western blotting, RT-PCR, transcription factor-specific reporter gene systems, mutant cells lacking the low affinity p75NTR NGF receptor and transfections of TNF?/NGF chimeric receptors were used to investigate signalling events associated with NGF/TNF?-promoted iNOS induction in PC12 cells. Results Our results show that iNOS expression resulting from NGF/TNF? combined treatment can be elicited in PC12 cells. Mutant PC12 cells lacking p75NTR did not respond, suggesting that p75NTR is required to mediate iNOS expression. Furthermore, cells transfected with chimeric TNF?/NGF receptors demonstrated that the simultaneous presence of both p75NTR and TrkA signaling is necessary to synergize with TNF? to mediate iNOS expression. Lastly, our data show that NGF/TNF?-promoted iNOS induction requires activation of the transcription factor nuclear factor kappa B (NF-?B. Conclusion Collectively, our in vitro model suggests that cells bearing both the high and low affinity NGF receptors may display increased sensitivity to TNF? in terms of iNOS expression and therefore be selectively at risk during acute (e.g. neurotrauma or chronic (e.g. neurodegenerative diseases conditions where high levels of pro-inflammatory cytokines in the nervous system occur pathologically. Our results also suggest that modulation of NF?B-promoted transcription of selective genes could serve as a potential therapeutic target to prevent neuroinflammation-induced neuronal damage.

  18. L/T-type and L/N-type calcium-channel blockers attenuate cardiac sympathetic nerve activity in patients with hypertension.

    Science.gov (United States)

    Ogura, Chika; Ono, Koh; Miyamoto, Shoichi; Ikai, Akiko; Mitani, Satoko; Sugimoto, Naozo; Tanaka, Shiro; Fujita, Masatoshi

    2012-12-01

    Sympathetic nerve activity is augmented by calcium-channel blocker treatment as a result of decreased blood pressure. Dihydropyridine calcium-channel blockers are divided into three different types. The purpose of the present study was to investigate whether treatment effects on hemodynamics, cardiac autonomic nerve activity and plasma norepinephrine levels differ among amlodipine (L type), efonidipine (L + T type) and cilnidipine (L + N type). We enrolled 14 hypertensive patients (seven males, seven females, 70?±?6 years old) undergoing a monotherapy of amlodipine, efonidipine or cilnidipine into this prospective, open-labeled, randomized, crossover study. At baseline and every 6 months of the treatment period, we repeated the evaluation of hemodynamics, spectral analysis of heart rate variability and plasma norepinephrine levels. Blood pressure and pulse rate were comparable among the three treatments. The low-frequency (LF)/high-frequency (HF) power ratio, an index of cardiac sympathovagal balance, was significantly lower with efonidipine and cilnidipine than with amlodipine, while the HF/total power ratio, an index of cardiac vagal activity, revealed the opposite results. There was no significant correlation between the LF/HF ratio and plasma norepinephrine levels. Antihypertensive monotherapy with efonidipine or cilnidipine attenuates cardiac sympathetic nerve activity more effectively than amlodipine monotherapy. PMID:22747420

  19. Mice and rats differ with respect to activity-dependent slowing of conduction velocity in the saphenous peripheral nerve.

    Science.gov (United States)

    Hoffmann, T; De Col, R; Messlinger, K; Reeh, P W; Weidner, C

    2015-04-10

    We assess in mice, the electrophysiological criteria developed in humans and rats in vivo for unmyelinated (C) fibre differentiation into sub-classes, derived from the activity-induced latency increase ("slowing") in response to electrical stimulation during 6min at 0.25Hz followed by 3min at 2Hz. Fibres are considered nociceptors if they show more than 10% slowing at 2Hz; nociceptors are further divided into mechanosensitive ("polymodal") and mechanoinsensitive ("silent") ones according to a latency shift of less and more than 1% during the first minute at 0.25Hz, respectively. Sympathetic postganglionics are recognised by 2-10% slowing at 2Hz; units slowing less than 2% at 2Hz remain uncategorised. For assessment of these criteria, we also developed a novel in vivo technique for recording of peripheral single-fibres in the mouse. We compared the theoretical slowing-rate discriminator criteria with experimental data obtained from mice in vivo/in vitro and rats in vitro. Out of 69 cutaneous mouse C-fibres in vitro and 19 in vivo, only 38 (67%) and 9 (47%) met the above 1% criterion, respectively; sympathetics were not identified. In contrast, out of 20 rats nerve fibres in vitro, 19 (95%) met this criterion. We conclude that (A) our novel electrophysiological technique is a practical method for examining mouse cutaneous single-fibres in vivo and (B) the published criterion for identifying silent nociceptors in rats and humans is not applicable in mice. PMID:25731910

  20. Functional and structural changes in the brain associated with the increase in muscle sympathetic nerve activity in obstructive sleep apnoea

    Directory of Open Access Journals (Sweden)

    Rania H. Fatouleh

    2014-01-01

    Full Text Available Muscle sympathetic nerve activity (MSNA is greatly elevated in patients with obstructive sleep apnoea (OSA during daytime wakefulness, leading to hypertension, but the underlying mechanisms are poorly understood. By recording MSNA concurrently with functional Magnetic Resonance Imaging (fMRI of the brain we aimed to identify the central processes responsible for the sympathoexcitation. Spontaneous fluctuations in MSNA were recorded via tungsten microelectrodes inserted percutaneously into the common peroneal nerve in 17 OSA patients and 15 healthy controls lying in a 3 T MRI scanner. Blood Oxygen Level Dependent (BOLD contrast gradient echo, echo-planar images were continuously collected in a 4 s ON, 4 s OFF (200 volumes sampling protocol. Fluctuations in BOLD signal intensity covaried with the intensity of the concurrently recorded bursts of MSNA. In both groups there was a positive correlation between MSNA and signal intensity in the left and right insulae, dorsolateral prefrontal cortex (dlPFC, dorsal precuneus, sensorimotor cortex and posterior temporal cortex, and the right mid-cingulate cortex and hypothalamus. In OSA the left and right dlPFC, medial PFC (mPFC, dorsal precuneus, anterior cingulate cortex, retrosplenial cortex and caudate nucleus showed augmented signal changes compared with controls, while the right hippocampus/parahippocampus signal intensity decreased in controls but did not change in the OSA subjects. In addition, there were significant increases in grey matter volume in the left mid-insula, the right insula, left and right primary motor cortices, left premotor cortex, left hippocampus and within the brainstem and cerebellum, and significant decreases in the mPFC, occipital lobe, right posterior cingulate cortex, left cerebellar cortex and the left and right amygdala in OSA, but there was no overlap between these structural changes and the functional changes in OSA. These data suggest that the elevated muscle vasoconstrictor drive in OSA may result from functional changes within these brain regions, which are known to be directly or indirectly involved in the modulation of sympathetic outflow via the brainstem. That there was no overlap in the structural and functional changes suggests that asphyxic damage due to repeated episodes of nocturnal obstructive apnoea is not the main cause of the sympathoexcitation.

  1. Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Suzuki, Tadashi; Kurabayashi, Masahiko [Gunma University School of Medicine, Department of Cardiovascular Medicine, Maebashi (Japan); Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan, Gunma (Japan)

    2005-03-01

    Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI). We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from {sup 99m}Tc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from {sup 201}Tl scintigraphy 3-5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment. Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from {sup 201}Tl and {sup 123}I-MIBG were significantly lower (26{+-}6 vs 30{+-}5, P<0.01, and 32{+-}8 vs 40{+-}6, P<0.0001, respectively), the H/M ratio significantly higher (1.99{+-}0.16 vs 1.77{+-}0.30, P<0.005) and the WR significantly lower (36%{+-}8% vs 44%{+-}12%, P<0.005) than in group B (n=25). Moreover, 6 months after treatment, LVEDV and LVEF were better in group A than in group B. These findings indicate that nicorandil can have beneficial effects on CSNA and left ventricular remodelling in patients with first anterior AMI. (orig.)

  2. Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction

    International Nuclear Information System (INIS)

    Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI). We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from 201Tl scintigraphy 3-5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment. Fifty patients originths after treatment. Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from 201Tl and 123I-MIBG were significantly lower (26±6 vs 30±5, P<0.01, and 32±8 vs 40±6, P<0.0001, respectively), the H/M ratio significantly higher (1.99±0.16 vs 1.77±0.30, P<0.005) and the WR significantly lower (36%±8% vs 44%±12%, P<0.005) than in group B (n=25). Moreover, 6 months after treatment, LVEDV and LVEF were better in group A than in group B. These findings indicate that nicorandil can have beneficial effects on CSNA and left ventricular remodelling in patients with first anterior AMI. (orig.)

  3. Wilms’ Tumor Gene 1 (WT1) Silencing Inhibits Proliferation of Malignant Peripheral Nerve Sheath Tumor sNF96.2 Cell Line

    OpenAIRE

    Parenti, Rosalba; Cardile, Venera; Graziano, Adriana Carol Eleonora; Parenti, Carmela; Venuti, Assunta; Bertuccio, Maria Paola; Furno, Debora Lo; Magro, Gaetano

    2014-01-01

    Wilms’ tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. WT1 expression has been variably reported in both benign and malignant peripheral nerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of the present study was to characterize its potential pathogenetic role in these relatively uncommon malignant tumors. Firstly, immunohistochemical analyses in MPNST sNF96.2 cell line showed stro...

  4. Transposition of DNase hypersensitive chromatin to the nuclear periphery coincides temporally with nerve growth factor-induced up-regulation of gene expression in PC12 cells.

    OpenAIRE

    Park, P. C.; Boni, U.

    1996-01-01

    To test the hypothesis that the nonrandom organization of the contents of interphase nuclei represents a compartmentalization of function, we examined the relative, spatial relationship of small nuclear ribonucleoproteins (snRNPs) and of DNase I hypersensitive chromatin (DHC) in rat pheochromocytoma cells. In controls, DHC and snRNPs colocalized as pan-nuclear speckles. During nerve growth factor-induced differentiation, both snRNPs and DHC migrated to the nuclear periphery with the migration...

  5. The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor.

    OpenAIRE

    Kordower, J. H.; Winn, S R; Liu, Y. T.; Mufson, E J; Sladek, J.R.; Hammang, J P; Baetge, E E; Emerich, D. F.

    1994-01-01

    Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricular transplants of polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reductions in ...

  6. Activated protein C modulates the proinflammatory activity of dendritic cells

    Science.gov (United States)

    Matsumoto, Takahiro; Matsushima, Yuki; Toda, Masaaki; Roeen, Ziaurahman; D’Alessandro-Gabazza, Corina N; Hinneh, Josephine A; Harada, Etsuko; Yasuma, Taro; Yano, Yutaka; Urawa, Masahito; Kobayashi, Tetsu; Taguchi, Osamu; Gabazza, Esteban C

    2015-01-01

    Background Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C-treated ovalbumin-pulsed dendritic cells had significantly less airway hyperresponsiveness, significantly decreased lung concentrations of Th1 and Th2 cytokines, and less plasma concentration of immunoglobulin E when compared to control mice. Conclusion These results suggest that dendritic cells mediate the immunosuppressive effect of activated protein C during allergic inflammation. PMID:26005353

  7. Evaluation of the retinal nerve fibre layer and ganglion cell complex thickness in pituitary macroadenomas without optic chiasmal compression.

    Science.gov (United States)

    Cennamo, G; Auriemma, R S; Cardone, D; Grasso, L F S; Velotti, N; Simeoli, C; Di Somma, C; Pivonello, R; Colao, A; de Crecchio, G

    2015-06-01

    PurposeThe aim of this prospective study was to measure the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex (GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of consecutive de novo patients with pituitary macroadenomas without chiasmal compression.Patients and methodsTwenty-two consecutive patients with pituitary macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2±14.6 years, 43 eyes) entered the study between September 2011 and June 2013. Among them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine females, nine males, mean age 36.47±6.37 years; 33 eyes) without pituitary adenoma, with normal ophthalmic examination, served as controls. In both patients and controls, cpRNFL and GCC thicknesses were measured by SD-OCT.ResultsPatients were significantly older (P=0.02) than controls. Best corrected visual acuity, intraocular pressure, colour fundus photography, and automatic perimetry test were within the normal range in patients and controls. Conversely, cpRNFL (P=0.009) and GCC (Pfibre layer thinning. SD-OCT may have a role in the early diagnosis and management of patients with pituitary tumours. PMID:25853400

  8. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells

    DEFF Research Database (Denmark)

    Galuska, Dana; Pirkmajer, Sergej

    2011-01-01

    Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary human renal tubular cells (HRTC) in control and hyperglycemic conditions.

  9. Nerve-cancer interactions in the stromal biology of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Ihsan EkinDemir

    2012-04-01

    Full Text Available Interaction of cancer cells with diverse cell types in the tumor stroma is today recognized to have a fate-determining role for the progression and outcome of human cancers. Despite the well-described interactions of cancer cells with several stromal components, i.e. inflammatory cells, cancer-associated fibroblasts, endothelial cells and pericytes, the investigation of their peculiar relationship with neural cells is still at its first footsteps. Pancreatic cancer (PCa with its abundant stroma represents one of the best-studied examples of a malignant tumor with a mutually trophic interaction between cancer cells and the intratumoral nerves embedded in the desmoplastic stroma. Nerves in PCa are a rich source of neurotrophic factors like nerve growth factor (NGF, glial-cell-derived neurotrophic factor (GDNF, artemin; of neuronal chemokines like fractalkine; and of autonomic neurotransmitters like norepinephrine which can all enhance the invasiveness of PCa cells via matrix-metalloproteinase (MMP upregulation, trigger neural invasion and activate pro-survival signaling pathways. Similarly, PCa cells themselves provide intrapancreatic nerves with abundant trophic agents which entail a remarkable neuroplasticity, leading to emergence of more routes for neural invasion and cancer spread, to augmented local neuro-surveillance, neural sensitization and neuropathic pain. The strong correlation of neural invasion with PCa-associated desmoplasia suggests the potential presence of a triangular relationship between nerves, PCa cells and other stromal partners like myofibroblasts and pancreatic stellate cells which generate tumor desmoplasia. Hence, although not a classical hallmark of human cancers, nerve-cancer interactions can be considered as an indispensable sub-class of cancer-stroma interactions in PCa. The present article provides an overview of the so far known nerve-cancer interactions in PCa and illustrates their ominous role in the stromal biology of human PCa.

  10. Nerve-Cancer Interactions in the Stromal Biology of Pancreatic Cancer

    Science.gov (United States)

    Demir, Ihsan Ekin; Friess, Helmut; Ceyhan, Güralp O.

    2012-01-01

    Interaction of cancer cells with diverse cell types in the tumor stroma is today recognized to have a fate-determining role for the progression and outcome of human cancers. Despite the well-described interactions of cancer cells with several stromal components, i.e., inflammatory cells, cancer-associated fibroblasts, endothelial cells, and pericytes, the investigation of their peculiar relationship with neural cells is still at its first footsteps. Pancreatic cancer (PCa) with its abundant stroma represents one of the best-studied examples of a malignant tumor with a mutually trophic interaction between cancer cells and the intratumoral nerves embedded in the desmoplastic stroma. Nerves in PCa are a rich source of neurotrophic factors like nerve growth factor (NGF), glial-cell-derived neurotrophic factor (GDNF), artemin; of neuronal chemokines like fractalkine; and of autonomic neurotransmitters like norepinephrine which can all enhance the invasiveness of PCa cells via matrix-metalloproteinase (MMP) upregulation, trigger neural invasion (NI), and activate pro-survival signaling pathways. Similarly, PCa cells themselves provide intrapancreatic nerves with abundant trophic agents which entail a remarkable neuroplasticity, leading to emergence of more routes for NI and cancer spread, to augmented local neuro-surveillance, neural sensitization, and neuropathic pain. The strong correlation of NI with PCa-associated desmoplasia suggests the potential presence of a triangular relationship between nerves, PCa cells, and other stromal partners like myofibroblasts and pancreatic stellate cells which generate tumor desmoplasia. Hence, although not a classical hallmark of human cancers, nerve-cancer interactions can be considered as an indispensable sub-class of cancer-stroma interactions in PCa. The present article provides an overview of the so far known nerve-cancer interactions in PCa and illustrates their ominous role in the stromal biology of human PCa. PMID:22529816

  11. Effect of cortisol on muscle sympathetic nerve activity in Pima Indians and Caucasians

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Weyer, Christian

    2003-01-01

    The hypothalamo-pituitary-adrenal axis and sympathetic nervous system (SNS) interact to maintain cardiovascular and metabolic homeostasis, especially during stress. Pima Indians have a low SNS activity, which may contribute to both their increased risk of obesity and reduced risk of hypertension. Although glucocorticoids inhibit SNS activity, Pima Indians are not hypercortisolemic compared with Caucasians. This does not exclude the possibility that the SNS is more responsive to an inhibitory effect of cortisol in the former than in the latter group. We measured fasting plasma ACTH and cortisol and muscle SNS activity [muscle sympathetic nervous system activity (MSNA), microneurography] in 58 males [27 Pimas/31 Caucasians]. Seven Pimas and 12 Caucasians were randomized to a double-blind, placebo-controlled, cross-over study to examine the effect of overnight partial chemical adrenalectomy (metyrapone) followed by cortisol replacement (hydrocortisone) on plasma ACTH, cortisol, and MSNA. There were no ethnic differences in fasting plasma ACTH or cortisol, but MSNA adjusted for percent body fat was lower in Pimas than in Caucasians (P <0.006). No correlation was found between fasting cortisol and basal MSNA. Administration of metyrapone did not lead to significant changes in MSNA. In response to a hydrocortisone infusion, MSNA decreased in Pima Indians (P = 0.03) but not in Caucasians (P = 0.7). Our data indicate that the low SNS activity that predisposes Pima Indians to obesity is not due to a tonic inhibitory effect of cortisol. However, an acute release of cortisol is likely to more effectively contain sympathoexcitation during stress in Pima Indians than in Caucasians, which may be an important mechanism of cardioprotection in this Native American population.

  12. The Neurotrophins Nerve Growth Factor, Brain-derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4 Are Survival and Activation Factors for Eosinophils in Patients with Allergic Bronchial Asthma

    OpenAIRE

    Nassenstein, Christina; Braun, Armin; Erpenbeck, Veit Johannes; Lommatzsch, Marek; Schmidt, Stephanie; Krug, Norbert; Luttmann, Werner; Renz, Harald; Virchow, Johann Christian

    2003-01-01

    Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood...

  13. Potential genotoxic effects of GSM-1800 exposure on human cutaneous and nerve cells

    International Nuclear Information System (INIS)

    Introduction The GSM-1800 signal has been in use for several years in Europe and questions raised about its potential biological effects, in view of the fact that, with respect to GSM-900, the increase in the carrier frequency corresponds to a more superficial absorption in the tissues. Consequently, the skin becomes an even more important target for the absorption of the radiofrequency radiation (R.F.R.) emitted by mobile phones. Nevertheless, brain tissues remain a critical target. Cells In order to determine whether R.F.R. at 1800 MHz could behave as a genotoxic agent, skin and brain cells were exposed to a 217-Hz-modulated GSM-1800 signal and assayed using the comet assay: (1) normal human epidermal keratinocytes (N.H.E.K.) and dermal fibroblasts (N.H.D.F.) which are cutaneous cells from epidermis and dermis respectively, and (2) the S.H. -S.Y.5.Y. and C.H.M.E.-5 human cell lines, which are neuroblastoma and micro-glial cells, respectively. Exposure The R.F.R. exposure system that was used in these experiments was manufactured by I.T. I.S. (Zurich, Switzerland). It consists in two shorted waveguides allowing to run exposed and sham conditions at the same time in the same culture incubator, at 37 Celsius degrees, 5% CO2. It is controlled by a software, which provides blind conditions until completion of data analysis. The specific absorption rate (S.A.R.) used was 2 W/kg, corresponding to the public exposure limit recommended by I.C.N.I.R.P. and the exposure duration was 48 hours. Comet assay At the end of the exposure, cells were removed from their Petri dish by trypsin/EDTA treatment, counted and 5 x 104 cells were used to detect DNA damage including single DNA breaks. Positive controls were performed using hydrogen peroxidase (1%, 1 hour). The genotoxic effects were detected using the alkaline comet assay kit (Trevigen slides) following the supplier procedure. Under these conditions, 6 independent experiments were performed for each cell type (2 Petri dishes by run). The analysis was done on at least 100 images from two comet slides (one per Petri dish) for each cellular model and exposure condition. Results The analysis of the slides is ongoing. Once the data analysis is completed, I.T.I.S. will break the blinding codes, and the results will be presented at the meeting. Acknowledgement: This work was supported by France Telecom R and D, Bouygues Telecom, the Cnrs and the Aquitaine Council for Research. (authors)

  14. Effects of oral contraceptives on sympathetic nerve activity during orthostatic stress in young, healthy women

    OpenAIRE

    Carter, Jason R.; Klein, Jenna C.; Schwartz, Christopher E.

    2009-01-01

    Recent studies report that the menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women. The purpose of the present study was to determine whether oral contraceptives (OC) influence sympathetic neural activation during an orthostatic challenge. Based on evidence that sympathetic baroreflex sensitivity (BRS) is increased during the “low hormone” (LH) phase (i.e., placebo pills) in women taking OC, we hypothesized an augmented muscle sympathetic...

  15. Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karasawa, Kensuke; Ayusawa, Mamoru; Noto, Nobutaka; Sumitomo, Naokata; Okada, Tomoo; Harada, Kensuke [Nihon Univ., Tokyo (Japan). School of Medicine

    2000-12-01

    Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5{+-}6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33{+-}0.22 in chronic heart failure class I, 2.50{+-}0.34 in class II, 1.95{+-}0.61 in class III, and 1.39{+-}0.29 in class IV (p<0.05). %WR was 24.8{+-}12.8% in chronic heart failure class I, 23.3{+-}10.2% in class II, 49.2{+-}24.5% in class III, and 66.3{+-}26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure. (author)

  16. Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

    International Nuclear Information System (INIS)

    Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5±6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33±0.22 in chronic heart failure class I, 2.50±0.34 in class II, 1.95±0.61 in class III, and 1.39±0.29 in class IV (p<0.05). %WR was 24.8±12.8% in chronic heart failure class I, 23.3±10.2% in class II, 49.2±24.5% in class III, and 66.3±26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and moror of therapeutic outcome and mortality in children with chronic heart failure. (author)

  17. Neutrophils Express Oncomodulin and Promote Optic Nerve Regeneration

    OpenAIRE

    Kurimoto, Takuji; Yin, Yuqin; Habboub, Ghaith; Gilbert, Hui-ya; Li, Yiqing; Nakao, Shintaro; Hafezi-moghadam, Ali; Benowitz, Larry I.

    2013-01-01

    Although neurons are normally unable to regenerate their axons after injury to the CNS, this situation can be partially reversed by activating the innate immune system. In a widely studied instance of this phenomenon, proinflammatory agents have been shown to cause retinal ganglion cells, the projection neurons of the eye, to regenerate lengthy axons through the injured optic nerve. However, the role of different molecules and cell populations in mediating this phenomenon remains unclear. We ...

  18. Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of neuropeptide Y signaling, and hypertension in adult life.

    Science.gov (United States)

    Rook, William; Johnson, Christopher D; Coney, Andrew M; Marshall, Janice M

    2014-12-01

    Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (?3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1-5 and 6-10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ?50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (?9 months; 139±3 versus 126±3 mm Hg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease. PMID:25267800

  19. Differentiation of immortal cells inhibits telomerase activity.

    OpenAIRE

    Sharma, H. W.; Sokoloski, J. A.; Perez, J. R.; Maltese, J. Y.; Sartorelli, A. C.; Stein, C. A.; Nichols, G.; Khaled, Z.; Telang, N. T.; Narayanan, R.

    1995-01-01

    Telomerase, a ribonucleic acid-protein complex, adds hexameric repeats of 5'-TTAGGG-3' to the ends of mammalian chromosomal DNA (telomeres) to compensate for the progressive loss that occurs with successive rounds of DNA replication. Although somatic cells do not express telomerase, germ cells and immortalized cells, including neoplastic cells, express this activity. To determine whether the phenotypic differentiation of immortalized cells is linked to the regulation of telomerase activity, t...

  20. The involvement of NF-?B in PDT-induced death of crayfish glial and nerve cells

    Science.gov (United States)

    Berezhnaya, E. V.; Neginskaya, M. A.; Kovaleva, V. D.; Rudkovskii, M. V.; Uzdensky, A. B.

    2015-03-01

    Photodynamic therapy (PDT) is used for selective destruction of cells, in particular, for treatment of brain tumors. However, photodynamic treatment damages not only tumor cells, but also healthy neurons and glial cells. To study the possible role of NF-?B in photodynamic injury of neurons and glial cells, we investigated the combined effect of photodynamic treatment and NF-?B modulators: activator betulinic acid, or inhibitors parthenolide and CAPE on an isolated crayfish stretch receptor consisting of a single neuron surrounded by glial cells. A laser diode (670 nm, 0.4 W/cm2) was used as a light source. The inhibition of NF-?B during PDT increased the duration of neuron firing and glial necrosis and decreased neuron necrosis and glial apoptosis. The activation of NF-?B during PDT increased neuron necrosis and glial apoptosis and decreased glial necrosis. The difference between the effects of NF-?B modulators on photosensitized neurons and glial cells indicates the difference in NF-?B-mediated signaling pathways in these cell types. Thus, NF-?B is involved in PDT-induced shortening of neuron firing, neuronal and glial necrosis, and apoptosis of glial cells.

  1. Minimum line width of ion beam-modified polystyrene by negative carbon ions for nerve-cell attachment and neurite extension

    International Nuclear Information System (INIS)

    The minimum line width of the negative-ion-modified polystyrene (PS) for guidance and immobilizations of nerve-cell body and neurite extension have been investigated. Carbon negative ions were implanted into PS at fluence of 3 x 1015 ions/cm2 and energy of 5-20 keV through the various triangle apertures of the micro-pattern mask. After in vitro culture of the nerve-like cells of rat adrenal pheochromocytoma (PC12h), results showed that the minimum line widths for a single cell attachment and for neurite extension were 5-7 and 3-5 ?m, respectively. While the minimum line width for attachment of cell group with long neurite was about 20 ?m. The suitable widths for a large number of cells and for neurite extension were 20 and 5 ?m, respectively. Therefore, the guidance for a clear separation of the attachment size of cell body and neurite extension could be achieved by the different modified line widths

  2. Anti-emetic and emetic effects of erythromycin in Suncus murinus: role of vagal nerve activation, gastric motility stimulation and motilin receptors.

    Science.gov (United States)

    Javid, Farideh A; Bulmer, David C; Broad, John; Aziz, Qasim; Dukes, George E; Sanger, Gareth J

    2013-01-15

    Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3 ± 1.8 to 4.0 ± 1.1 emetic episodes at 5mg/kg) or by nicotine (from 9.5 ± 2.0 to 3.1 ± 2.0 at 5mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 ?M or atropine 1 ?M, facilitated by l-NAME 300 ?M) were facilitated by motilin (1-100 nM) and erythromycin (10-30 ?M). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin. PMID:23201066

  3. Evaluation of sympathetic nerve system activity with MIBG. Comparison with heart rate variability

    International Nuclear Information System (INIS)

    Authors attempted to elucidate the relations of plasma concentration of norepinephrine (pNE) and findings of heart rate variability and MIBG myocardial scintigraphy and evaluated cardiac autonomic nervous activity in chronic renal failure. Subjects were 211 patients with various heart diseases (coronary artery lesion, cardiomyopathy, hypertension, diabetes mellitus, renal failure and so on), 60 patients with artificial kidney due to chronic renal failure, 13 of whom were found to have coronary arterial disease by Tl myocardial scintigraphy, and 14 normal volunteers. ECG was recorded with the portable recorder for heart rate variability. Together with collection of blood for pNE measurement, myocardial scintigraphy was done at 15 and 150 min after intravenous administration of 111 MBq of MIBG for acquisition of early and delayed, respectively, images of the frontal breast. Accumulation at and elimination during the time points of MIBG were computed in cps unit. Variability of heart rate was found to have the correlation positive with MIBG delayed accumulation and negative with the elimination, and pNE, negative with heart rate variability and the delayed accumulation and positive with the elimination. Thus cardiac autonomic nervous abnormality was suggested to occur before uremic cardiomyopathy. (K.H.)

  4. Measuring acute changes in adrenergic nerve activity of the heart in the living animal

    International Nuclear Information System (INIS)

    Changes in the function of the adrenergic neurons of the heart may be important indicators of the adaptations of an animal to physiologic stress and disease. Rates of loss of norepinephrine (NE) from the heart were considered to be proportional to NE secretion and to adrenergic function. In rat hearts, yohimbine induced almost identical increases in rates of loss of 3H-NE and of 125I-metaiodobenzylguanidine (MIBG), a functional analog of NE. Clonidine induced decreases in rates of loss of 3H-NE that were also mimicked by those of 125I-MIBG. In the dog heart, pharmacologically-induced increases and decreases in rates of loss of 123I-MIBG could be measured externally; these values were similar to those obtained for 125I-MIBG in the rat heart. Thus acute changes in the adrenergic neuron activity can be measured in the living heart. The method is applicable to man in determining the capacity of the adrenergic system to respond to provocative challenges

  5. Laminin-based Nanomaterials for Peripheral Nerve Tissue Engineering

    Science.gov (United States)

    Neal, Rebekah Anne

    Peripheral nerve transection occurs commonly in traumatic injury, causing motor and sensory deficits distal to the site of injury. One option for surgical repair is the nerve conduit. Conduits currently on the market are hollow tubes into which the nerve ends are sutured. Although these conduits fill the gap, they often fail due to the slow rate of regeneration over long gaps. To facilitate increased speed of regeneration and greater potential for functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in peripheral nerve regeneration. In this dissertation, I fabricated laminin-1 and laminin-polycaprolactone (PCL) blend nanofibers that mimic the geometry and functionality of the peripheral nerve basement membrane. These fibers resist hydration in aqueous media and require no harsh chemical crosslinkers. Adhesion and differentiation of both neuron-like and neuroprogenitor cells is improved on laminin nanofibrous meshes over two-dimensional laminin substrates. Blend meshes with varying laminin content were characterized for composition, tensile properties, degradation rates, and bioactivity in terms of cell attachment and axonal elongation. I have established that 10% (wt) laminin content is sufficient to retain the significant neurite-promoting effects of laminin critical in peripheral nerve repair. In addition, I utilized modified collector plate design to manipulate electric field gradients during electrospinning for the fabrication of aligned nanofibers. These aligned substrates provide enhanced directional guidance cues to the regenerating axons. Finally, I replicated the clinical problem of peripheral nerve transection using a rat tibial nerve defect model for conduit implantation. When the lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment, I observed significant recovery of sensory and motor function over six weeks. This recovery was supported by nerve conduction studies and electromyography which described impulse transmission, muscle stimulation, and foot twitch through the region of regeneration. These studies provide a firm foundation for the use of natural-synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. The similarity in surgical technique and obvious benefit to the patient should lead to rapid translation into clinical application.

  6. Optic Nerve Pit

    Science.gov (United States)

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Pit What is optic nerve pit? An optic nerve pit is a ... may be seen in both eyes. How is optic pit diagnosed? If the pit is not affecting ...

  7. Evaluating Optic Nerve Damage: Pearls and Pitfalls

    OpenAIRE

    Mackenzie, Paul J.; Mikelberg, Frederick S.

    2009-01-01

    Primary open-angle glaucoma is a progressive optic neuropathy involving loss of retinal ganglion cells and their axons at the level of the optic nerve head. This change manifests as thinning and excavation of the neural tissues and nerve fiber layer. Therefore, it has long been known that the structural appearance of the optic nerve head is paramount to both glaucoma diagnosis and to the detection of progression [1-4]. Quantitative imaging methods such as Heidelberg Retinal Tomography (HRT) a...

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

    Science.gov (United States)

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

    2015-06-01

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

  9. Analysis of the relationship between muscle sympathetic nerve activity and cardiac 123I-metaiodobenzylguanidine uptake in patients with Parkinson's disease.

    Science.gov (United States)

    Shindo, Kazumasa; Kaneko, Eri; Watanabe, Harue; Sugimoto, Tetsuhiko; Ohta, Emiko; Ohashi, Kenji; Nagasaka, Takamura; Shiozawa, Zenji

    2005-11-01

    To analyze the correlation between muscle sympathetic nerve activity (MSNA) and cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD), we measured both parameters in 14 PD patients who were 51 to 82 years of age (mean, 63.1 +/- 8.7 years). The duration of PD was 2 to 26 years, and the disability level (modified Hoehn and Yahr stage) ranged from 2.0 to 4.0 (mean, 3.2 +/- 0.5). MSNA was recorded from the peroneal nerve fascicles using microneurographic methods, and then cardiac MIBG scintigraphy was performed within 1 month. We analyzed the correlation between the standardized MSNA, expressed as a percentage of the predicted value based on control subject data, and the heart-to-mediastinum ratio (H/M) or washout ratio (WR) from early and delayed MIBG images. The relationships between disease duration or disability and MSNA, the H/M ratio, or the WR were also analyzed. No significant correlations were found between MSNA and H/M ratio or WR. Although MSNA was inversely correlated with disease duration and with disability level, neither the H/M ratio nor the WR showed a significant correlation with disease duration or disability level. Because MSNA and MIBG abnormalities were not related, functional changes in addition to organic changes in cardiac sympathetic nerve endings may result in abnormal uptake of MIBG in Parkinson's disease. . PMID:16007621

  10. Optic nerve invasion of uveal melanoma.

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Isager, Peter

    2007-01-01

    The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve invasion. Prelaminar/laminar optic nerve invasion was in multivariate analysis associated with focal retinal invasion, neovascularization of the chamber angle, and scleral invasion. Postlaminar invasion was further associated with non-spindle cell type and rupture of the inner limiting membrane of the retina. The optic nerve was invaded in four different ways: 1) by tumor extension from the neuroretina through the lamina cribrosa; 2) by direct extension into the optic nerve head between Bruch's membrane and the border tissue of Elschnig; 3) by direct invasion through the border tissue of Elschnig; and 4) in one case a tumor spread along the inner limiting membrane to the optic nerve through the lamina cribrosa. Invasion of the optic nerve had no impact on all-cause mortality or melanoma-related mortality in multivariate analyses. The majority of melanomas invading the optic nerve are large juxtapapillary tumors invading the optic nerve because of simple proximity to the nerve. A neurotropic subtype invades the optic nerve and retina in a diffuse fashion unrelated to tumor size or location. Udgivelsesdato: 2007-Jan

  11. Subdiaphragmatic vagus nerve activity and hepatic venous glucose are differentially regulated by the central actions of insulin in Wistar and SHR.

    Science.gov (United States)

    Ribeiro, Izabela Martina R; Ferreira-Neto, Hildebrando C; Antunes, Vagner R

    2015-05-01

    Glucose is the most important energy substrate for the maintenance of tissues function. The liver plays an essential role in the control of glucose production, since it is able to synthesize, store, and release glucose into the circulation under different situations. Hormones like insulin and catecholamines influence hepatic glucose production (HGP), but little is known about the role of the central actions of physiological doses of insulin in modulating HGP via the autonomic nervous system in nonanesthetized rats especially in SHR where we see a high degree of insulin resistance and metabolic dysfunction. Wistar and SHR received ICV injection of insulin (100 nU/?L) and hepatic venous glucose concentration (HVGC) was monitored for 30 min, as an indirect measure of HGP. At 10 min after insulin injection, HVGC decreased by 27% in Wistar rats, with a negligible change (3%) in SHR. Pretreatment with atropine totally blocked the reduction in HVGC, while pretreatment with propranolol and phentolamine induced a decrease of 8% in HVGC after ICV insulin injection in Wistar. Intracarotid infusion of insulin caused a significant increase in subdiaphragmatic vagus nerve (SVN) activity in Wistar (12 ± 2%), with negligible effects on the lumbar splanchnic sympathetic nerve (LSSN) activity (-6 ± 3%). No change was observed in SVN (-2 ± 2%) and LSSN activities (2 ± 3%) in SHR after ICA insulin infusion. Taken together, these results show, in nonanesthetized animals, the importance of the parasympathetic nervous system in controlling HVGC, and subdiaphragmatic nerve activity following central administration of insulin; a mechanism that is impaired in the SHR. PMID:25948821

  12. Nitrooleic Acid, an Endogenous Product of Nitrative Stress, Activates Nociceptive Sensory Nerves via the Direct Activation of TRPA1

    OpenAIRE

    Taylor-clark, Thomas E.; Ghatta, Srinivas; Bettner, Weston; Undem, Bradley J.

    2009-01-01

    Transient Receptor Potential A1 (TRPA1) is a nonselective cation channel, preferentially expressed on a subset of nociceptive sensory neurons, that is activated by a variety of reactive irritants via the covalent modification of cysteine residues. Excessive nitric oxide during inflammation (nitrative stress), leads to the nitration of phospholipids, resulting in the formation of highly reactive cysteine modifying agents, such as nitrooleic acid (9-OA-NO2). Using calciu...

  13. Protective effects of Ginkgo biloba extract on morphology and function of retinal ganglion cells after optic nerve transection in guinea pigs

    Directory of Open Access Journals (Sweden)

    Zheng-gao XIE

    2009-10-01

    Full Text Available Objective: To investigate the effects of Ginkgo biloba extract (EGb 761 on the morphology and function of retinal ganglion cells (RGC in guinea pigs with optic nerve transection. Methods: Seventy-five albino guinea pigs were randomly divided into five groups: normal control group, sham-operated group, untreated group, normal saline group and EGb 761 group. No operation was performed in the normal control group. Optic nerve was merely exposed in the sham-operated group, but transected at 1.0 mm from posterior pole of the eye ball in the untreated, normal saline and EGb 761 groups. Guinea pigs in the EGb 761 group or the normal saline group received daily intraperitoneal injection of EGb 761 (100 mg/kg or corresponding volume of normal saline from 7 days before experiment to 28 days after experiment. Three guinea pigs in each group were sacrificed for apoptosis assay (TUNEL method of RGC. Pattern electoretinograms (PERGs were recorded 14 and 28 days after transection, respectively. At the end of the examination, six guinea pigs were killed for histological examination and RGC count.Results: No TUNEL-positive cells were observed in the normal control, sham-operated and EGb 761 groups, but there were TUNEL-positive cells in the untreated group and the normal saline group. The numbers of RGCs in the untreated and normal saline groups were less than those in the normal control and sham-operated groups at 14 days or 28 days (P0.05 at 14 days or 28 days. The number of RGCs was positive correlated to N95 amplitude (r=0.859, P=0.001 5.Conclusion: EGb 761 can inhibit the apoptosis of RGCs in guinea pigs after optic nerve transection, thus protect the morphology and function of RGCs.

  14. Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Suzuki, Tadashi; Kurabayashi, Masahiko [Gunma University School of Medicine, Department of Cardiovascular Medicine, Maebashi, Gunma (Japan); Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan, Department of Internal Medicine, Gunma (Japan)

    2005-08-01

    The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33{+-}7%] were randomly assigned to perindopril (2 mg/day; n=20) or enalapril (5 mg/day; n=20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. After treatment, in patients receiving perindopril, TDS decreased from 39{+-}10 to 34{+-}9 (P<0.01), H/M ratios increased from 1.62{+-}0.27 to 1.76{+-}0.29 (P<0.01), WR decreased from 50{+-}14% to 42{+-}14% (P<0.05) and plasma BNP concentrations decreased from 226{+-}155 to 141{+-}90 pg/ml (P<0.0005). In addition, the LVEDV decreased from 180{+-}30 to 161{+-}30 ml (P<0.05) and the LVESV decreased from 122{+-}35 to 105{+-}36 ml (P<0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33{+-}8% to 36{+-}12%; P=NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. Plasma BNP concentrations, {sup 123}I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF. (orig.)

  15. In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration.

    Science.gov (United States)

    Das, Suradip; Sharma, Manav; Saharia, Dhiren; Sarma, Kushal Konwar; Sarma, Monalisa Goswami; Borthakur, Bibhuti Bhusan; Bora, Utpal

    2015-09-01

    We report a novel silk-gold nanocomposite based nerve conduit successfully tested in a neurotmesis grade sciatic nerve injury model in rats over a period of eighteen months. The conduit was fabricated by adsorbing gold nanoparticles onto silk fibres and transforming them into a nanocomposite sheet by electrospinning which is finally given a tubular structure by rolling on a stainless steel mandrel of chosen diameter. The conduits were found to promote adhesion and proliferation of Schwann cells in vitro and did not elicit any toxic or immunogenic responses in vivo. We also report for the first time, the monitoring of muscular regeneration post nerve conduit implantation by recording motor unit potentials (MUPs) through needle electromyogram. Pre-seeding the conduits with Schwann cells enhanced myelination of the regenerated tissue. Histo-morphometric and electrophysiological studies proved that the nanocomposite based conduits pre-seeded with Schwann cells performed best in terms of structural and functional regeneration of severed sciatic nerves. The near normal values of nerve conduction velocity (50 m/sec), compound muscle action potential (29.7 mV) and motor unit potential (133 ?V) exhibited by the animals implanted with Schwann cell loaded nerve conduits in the present study are superior to those observed in previous reports with synthetic materials as well as collagen based nerve conduits. Animals in this group were also able to perform complex locomotory activities like stretching and jumping with excellent sciatic function index (SFI) and led a normal life. PMID:26026910

  16. The nuclear events guiding successful nerve regeneration

    OpenAIRE

    SumikoKiryu-Seo

    2011-01-01

    Peripheral nervous system (PNS) neurons survive and regenerate after nerve injury, whereas central nervous system (CNS) neurons lack the capacity to do so. The inability of the CNS to regenerate presumably results from a lack of intrinsic growth activity and a permissive environment. To achieve CNS regeneration, we can learn from successful nerve regeneration in the PNS. Neurons in the PNS elicit dynamic changes in gene expression in response to permissive environmental cues following nerve i...

  17. Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1

    OpenAIRE

    Marsick, Bonnie M.; Flynn, Kevin C.; Santiago-Medina, Miguel; Bamburg, James R; Letourneau, Paul C

    2010-01-01

    Proper neural circuitry requires that growth cones, motile tips of extending axons, respond to molecular guidance cues expressed in the developing organism. However, it is unclear how guidance cues modify the cytoskeleton to guide growth cone pathfinding. Here we show acute treatment with two attractive guidance cues, nerve growth factor (NGF) and netrin-1, for embryonic dorsal root ganglion and temporal retinal neurons, respectively, results in increased growth cone membrane protrusion, acti...

  18. Role of intrahepatic innervation in regulating the activity of liver cells

    OpenAIRE

    Streba, Letitia Adela Maria; Vere, Cristin Constantin; Ionescu, Alin Gabriel; Streba, Costin Teodor; Rogoveanu, Ion

    2014-01-01

    Liver innervation comprises sympathetic, parasympathetic and peptidergic nerve fibers, organized as either afferent or efferent nerves with different origins and roles. Their anatomy and physiology have been studied in the past 30 years, with different results published over time. Hepatocytes are the main cell population of the liver, making up almost 80% of the total liver volume. The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and s...

  19. Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair / Respostas astrocitárias na medula espinal do rato submetido ao esmagamento duplo do nervo ciático e tratado com injeção local de suspensão de células de Schwann cultivadas ou de extrato de medula espinal lesada: implicações na terapia celular para o reparo do nervo

    Scientific Electronic Library Online (English)

    João Gabriel Martins, Dallo; Bernardo Vergara, Reichert; José Benedito Ramos, Valladão Júnior; Camila, Silva; Bianca Aparecida de, Luca; Beatriz de Freitas Azevedo, Levy; Gerson, Chadi.

    2007-12-01

    Full Text Available OBJETIVO: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS), um tipo de glia periférica, também reagem com a lesão do nervo, pode [...] ndo interferir com o reparo e cicatrização, crescimento de fibras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ciático poder alterar o padrão da ativação astrocitária nos cornos anterior e posterior da medula espinal do rato. MÉTODOS: Suspensão de CS cultivadas ou extrato homogeneizado de medula espinal lesada de rato foram inoculados num reservatório feito a partir de dois esmagamentos aplicados no nervo ciático do rato distantes 0,5mm entre si. Injeção local de salina tamponada serviu como controle. Os ratos foram mortos uma semana após e os astrócitos da medula espinal marcados por método imunohistoquímico e quantificados por análise de imagem. RESULTADOS: No corno anterior da medula, ipsilateral à lesão, ativação astrocitária leve foi vista após as injeções de tampão ou CS, entretanto, ativação celular intensa foi observada nesta região com a inoculação neural do extrato homogeneizado de tecido medular lesado. Adicionalmente, as inoculações de CS e de extrato homogeneizado de tecido medular promoveram forte reação astrocitária no corno dorsal da medula espinal, bilateralmente. CONCLUSÕES: Os astrócitos da medula espinal reagem em função do processo de reparo do nervo lesado, o que pode influenciar o resultado funcional esperado, algo que deve ser considerado durante o planejamento da estratégia neurocirúrgica. Abstract in english PURPOSE: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fibe [...] r outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. METHODS: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS) served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantified by means of quantitative image analysis. RESULTS: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may influence the functional outcome. The event should be considered during the neurosurgery strategies.

  20. Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair Respostas astrocitárias na medula espinal do rato submetido ao esmagamento duplo do nervo ciático e tratado com injeção local de suspensão de células de Schwann cultivadas ou de extrato de medula espinal lesada: implicações na terapia celular para o reparo do nervo

    Directory of Open Access Journals (Sweden)

    João Gabriel Martins Dallo

    2007-12-01

    Full Text Available PURPOSE: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC, a peripheral glia, also react after nerve lesion favoring wound/repair, fiber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. METHODS: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantified by means of quantitative image analysis. RESULTS: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may influence the functional outcome. The event should be considered during the neurosurgery strategies.OBJETIVO: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS, um tipo de glia periférica, também reagem com a lesão do nervo, podendo interferir com o reparo e cicatrização, crescimento de fibras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ciático poder alterar o padrão da ativação astrocitária nos cornos anterior e posterior da medula espinal do rato. MÉTODOS: Suspensão de CS cultivadas ou extrato homogeneizado de medula espinal lesada de rato foram inoculados num reservatório feito a partir de dois esmagamentos aplicados no nervo ciático do rato distantes 0,5mm entre si. Injeção local de salina tamponada serviu como controle. Os ratos foram mortos uma semana após e os astrócitos da medula espinal marcados por método imunohistoquímico e quantificados por análise de imagem. RESULTADOS: No corno anterior da medula, ipsilateral à lesão, ativação astrocitária leve foi vista após as injeções de tampão ou CS, entretanto, ativação celular intensa foi observada nesta região com a inoculação neural do extrato homogeneizado de tecido medular lesado. Adicionalmente, as inoculações de CS e de extrato homogeneizado de tecido medular promoveram forte reação astrocitária no corno dorsal da medula espinal, bilateralmente. CONCLUSÕES: Os astrócitos da medula espinal reagem em função do processo de reparo do nervo lesado, o que pode influenciar o resultado funcional esperado, algo que deve ser considerado durante o planejamento da estratégia neurocirúrgica.

  1. Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

    OpenAIRE

    Howell, Gareth R; Soto, Ileana; Zhu, Xianjun; Ryan, Margaret; Macalinao, Danilo G.; Sousa, Gregory L.; Caddle, Lura B.; MacNicoll, Katharine H.; Barbay, Jessica M.; Porciatti, Vittorio; Anderson, Michael G.; Smith, Richard S.; Clark, Abbot F; Libby, Richard T; John, Simon W.M

    2012-01-01

    Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disea...

  2. Nervous System, Neurons, Nerves

    Science.gov (United States)

    How does the nervous system work? It is a question that has engaged the minds of scientists, doctors, and others for centuries. The National Science Teachers Association (NSTA) has created this tour of the nervous system for teachers and students. First-time visitors can start with the Explore a Nerve Cell area, which goes over the membrane, nucleus, axon, dendrites, and the synapse in exquisite detail with interactive graphics. Moving on, The Basics area provides summaries of the operation of the nervous system and a rather illustrative area named Ouch! The site is rounded out by the Nervous Systems Explorations section, which has some nice simulations covering Brainstorms and Simple Reflexes.

  3. An effect of wrapping peripheral nerve anastomosis with pedicled muscle flap on nerve regeneration in experiment

    Directory of Open Access Journals (Sweden)

    Naumenko L.Yu.

    2010-01-01

    Full Text Available Despite intrinsic capacity of peripheral nerves to regenerate, functional outcomes of peripheral nerves injury remain poor. Nerve ischemia, intra-/perineurial fibrosis and neuroma formation contribute a lot to that. Several authors demonstrated beneficial effects of increased vascularization at the site of injury on peripheral nerves regeneration. The use of highly vascularized autologous tissues (greater omentum as a source of peripheral nerves neovascularization shows promising re-sults. We proposed a surgical technique in which injured peripheral nerves anastomosis was wrapped in a pedicled muscular flap and performed morphological assessment of the efficacy of such technique with the aid of immunohistochemistry. 14 rats (which underwent sciatic nerve transection were operated according to proposed technique. Another 14 rats, in which only end-to-end nerve anastomosis (without muscular wrapping was performed served as controls. Morphological changes were evaluated at 3 weeks and 3 months periods. Higher blood vessel and axon counts were observed in experimental groups at both checkpoints. There was also an increase in Schwann cells and macrophages counts, and less collagen content in pe-ripheral nerves of experimental groups. Axons in neuromas of experimental groups showed a higher degree of arrangement. We conclude that proposed surgical technique provides better vascularisation of injured peripheral nerves, which is beneficial for nerve regeneration.

  4. Activated protein C modulates the proinflammatory activity of dendritic cells

    Directory of Open Access Journals (Sweden)

    Matsumoto T

    2015-05-01

    Full Text Available Takahiro Matsumoto,1,2* Yuki Matsushima,1* Masaaki Toda,1 Ziaurahman Roeen,1 Corina N D'Alessandro-Gabazza,1,5 Josephine A Hinneh,1 Etsuko Harada,1,3 Taro Yasuma,4 Yutaka Yano,4 Masahito Urawa,1,5 Tetsu Kobayashi,5 Osamu Taguchi,5 Esteban C Gabazza1 1Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, 2BONAC Corporation, BIO Factory 4F, Fukuoka, 3Iwade Research Institute of Mycology, 4Department of Endocrinology, Diabetes and Metabolism, 5Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan *These authors contributed equally to this work Background: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C-treated ovalbumin-pulsed dendritic cells had significantly less airway hyperresponsiveness, significantly decreased lung concentrations of Th1 and Th2 cytokines, and less plasma concentration of immunoglobulin E when compared to control mice. Conclusion: These results suggest that dendritic cells mediate the immunosuppressive effect of activated protein C during allergic inflammation. Keywords: allergy, dendritic cells, coagulation, protein C pathway

  5. Active Gel Model of Amoeboid Cell Motility

    CERN Document Server

    Callan-Jones, A C

    2013-01-01

    We develop a model of amoeboid cell motility based on active gel theory. Modeling the motile apparatus of a eukaryotic cell as a confined layer of finite length of poroelastic active gel permeated by a solvent, we first show that, due to active stress and gel turnover, an initially static and homogeneous layer can undergo a contractile-type instability to a polarized moving state in which the rear is enriched in gel polymer. This agrees qualitatively with motile cells containing an actomyosin-rich uropod at their rear. We find that the gel layer settles into a steadily moving, inhomogeneous state at long times, sustained by a balance between contractility and filament turnover. In addition, our model predicts an optimal value of the gel-susbstrate adhesion leading to maximum layer speed, in agreement with cell motility assays. The model may be relevant to motility of cells translocating in complex, confining environments that can be mimicked experimentally by cell migration through microchannels.

  6. IL-10 and NOS2 Modulate Antigen-Specific Reactivity and Nerve Infiltration by T Cells in Experimental Leprosy

    OpenAIRE

    Hagge, Deanna A.; Scollard, David M.; Ray, Nashone A.; Marks, Vilma T.; Deming, Angelina T.; Spencer, John S.; Adams, Linda B.

    2014-01-01

    Despite effective antimicrobial therapy, 30–50% of leprosy patients develop immunological complications called leprosy reactions before, during or even years after being cured. Leprosy reactions are a major risk for neuritis that leads to peripheral nerve damage, disfigurement and disability. Unfortunately, why and how leprosy reactions occur is not well understood. Based on the latest human genetic leprosy susceptibility research and mouse infection models, we generated a double knockout m...

  7. Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure. Comparison with enalapril

    International Nuclear Information System (INIS)

    In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II delayed heart/mediastinum count ratio was significantly increased (2.0±0.07 vs 2.15±0.07, p=0.013) and the washout rate was significantly decreased (33.0±1.4 vs 30.5±1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP. (author)

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

    Directory of Open Access Journals (Sweden)

    Jiang Xinquan

    2011-07-01

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

  9. Perivascular demyelination and intramyelinic oedema in reperfusion nerve injury.

    OpenAIRE

    Nukada, H.; Mcmorran, P. D.

    1994-01-01

    Nerve ischaemia plays a major role in the development of pathological alterations in various neuropathies, and the effects of ischaemia are amplified by reperfusion in various tissues. While pathological alterations in acutely ischaemic nerve have been established, nerve pathology resulting from reperfusion injury has never been elucidated. To evaluate what cell type in peripheral nerve is affected by reoxygenation following a hypoxic episode, we developed an animal model of transient severe ...

  10. Protein kinase- and staurosporine-dependent induction of neurite outgrowth and plasminogen activator activity in PC12 cells.

    Science.gov (United States)

    Leprince, P; Bonvoisin, C; Rogister, B; Mazy-Servais, C; Moonen, G

    1996-11-01

    We analysed how interactions between protein kinase-dependent intracellular signalling pathways were implicated in the control of the production of tissue-type plasminogen activator (tPA) and the generation of neurite outgrowth by PC12 cells. To that aim, cells were treated with agents that interact with the trk receptor and with protein kinases A and C. Nerve growth factor induced only the formation of large neurites. The release of the protease and the production of short neurite outgrowth were found to be protein-kinase-A-dependent events that could be enhanced by simultaneous activation of protein kinase C with phorbol ester. At high concentration, staurosporine, a nonselective inhibitor of protein kinases, induced the production of short neurites and mimicked the protein-kinase-A-dependent effect on tPA release. Such a response was not observed with K-252a, an analogue of staurosporine devoid of neurite-outgrowth-promoting activity. The responses to protein kinase A stimulation and the addition of staurosporine, although similar, seemed to occur through an activation of distinct, yet interacting, signalling pathways. In conclusion, tPA release and large neurite outgrowth from PC12 cells are controlled by parallel, albeit interacting, pathways, suggesting that these two potentially antagonistic events in PC12 cell differentiation can be modulated in a concerted way or independently of each other, depending on the activity of several protein kinases. PMID:8937450

  11. Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy. A comparison of 123I-MIBG scintigraphic and echocardiographic data

    International Nuclear Information System (INIS)

    It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123I-MIBG scintigraphy. Both of these methods are associated with ?-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patents with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography; and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123[123I]meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r=0.682, p=0.0146), wall motion after dobutamine stress (r=0.758, p=0.0043), the change in wall motion (r=0.667, p=0.0178), and with left ventricular diastolic diameter (r=0.837, p=0.0007). In addition, the 123I-MIBG washout rate correlated with baseline wall motion (r=0.608, p=0.0360), wall motion after dobutamine stress (r=0.703, p=0.0107), and with the change in wall motion (r=0.664, p=0.0185). Wall motion, especia(r=0.664, p=0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure. (author)

  12. Activity driven fluctuations in living cells

    CERN Document Server

    Fodor, É; Gov, N S; Visco, P; Weitz, D A; van Wijland, F

    2015-01-01

    We propose a model for the dynamics of a probe embedded in a living cell, where both thermal fluctuations and nonequilibrium activity coexist. The model is based on a confining harmonic potential describing the elastic cytoskeletal matrix, which undergoes random active hops as a result of the nonequilibrium rearrangements within the cell. We describe the probe's statistics and we bring forth quantities affected by the nonequilibrium activity. We find an excellent agreement between the predictions of our model and experimental results for tracers inside living cells. Finally, we exploit our model to arrive at quantitative predictions for the parameters characterizing nonequilibrium activity, such as the typical time scale of the activity and the amplitude of the active fluctuations.

  13. The ErbB2 inhibitor Herceptin (Trastuzumab) promotes axonal outgrowth four weeks after acute nerve transection and repair.

    Science.gov (United States)

    Placheta, Eva; Hendry, J Michael; Wood, Matthew D; Lafontaine, Christine W; Liu, Edward H; Cecilia Alvarez Veronesi, M; Frey, Manfred; Gordon, Tessa; Borschel, Gregory H

    2014-10-17

    Accumulating evidence suggests that neuregulin, a potent Schwann cell mitogen, and its receptor, ErbB2, have an important role in regulating peripheral nerve regeneration. We hypothesized that Herceptin (Trastuzumab), a monoclonal antibody that binds ErbB2, would disrupt ErbB2 signaling, allowing us to evaluate ErbB2's importance in peripheral nerve regeneration. In this study, the extent of peripheral motor and sensory nerve regeneration and distal axonal outgrowth was analyzed two and four weeks after common peroneal (CP) nerve injury in rats. Outcomes analyzed included neuron counts after retrograde labeling, histomorphometry, and protein analysis. The data analysis revealed that there was no impact of Herceptin administration on either the numbers of motor or sensory neurons that regenerated their axons but histomorphometry revealed that Herceptin significantly increased the number of regenerated axons in the distal repaired nerve after 4 weeks. Protein analysis with Western blotting revealed no difference in either expression levels of ErbB2 or the amount of activated, phosphorylated ErbB2 in injured nerves. In conclusion, administration of the ErbB2 receptor inhibitor after nerve transection and surgical repair did not alter the number of regenerating neurons but markedly increased the number of regenerated axons per neuron in the distal nerve stump. Enhanced axon outgrowth in the presence of this ErbB2 inhibitor indicates that ErbB2 signaling may limit the numbers of axons that are emitted from each regenerating neuron. PMID:25220708

  14. Ganglion cell complex and retinal nerve fiber layer measured by fourier-domain optical coherence tomography for early detection of structural damage in patients with preperimetric glaucoma

    Directory of Open Access Journals (Sweden)

    Rolle T

    2011-07-01

    Full Text Available Teresa Rolle, Cristina Briamonte, Daniela Curto, Federico Maria GrignoloEye Clinic, Section of Ophthalmology, Department of Clinical Physiopathology, University of Torino, Torino, ItalyAims: To evaluate the capability of Fourier-domain optical coherence tomography (FD-OCT to detect structural damage in patients with preperimetric glaucoma.Methods: A total of 178 Caucasian subjects were enrolled in this cohort study: 116 preperimetric glaucoma patients and 52 healthy subjects. Using three-dimensional FD-OCT, the participants underwent imaging of the ganglion cell complex (GCC and the optic nerve head. Sensitivity, specificity, likelihood ratios, and predictive values were calculated for all parameters at the first and fifth percentiles. Areas under the curves (AUCs were generated for all parameters and were compared (Delong test. For both the GCC and the optic nerve head protocols, the OR logical disjunction (Boolean logic operator was calculated.Results: The AUCs didn’t significantly differ. Macular global loss volume had the largest AUC (0.81. Specificities were high at both the fifth and first percentiles (up to 97%, but sensitivities were low, especially at the first percentile (55%–27%.Conclusion: Macular and papillary diagnostic accuracies did not differ significantly based on the 95% confidence interval. The computation of the Boolean OR operator has been found to boost diagnostic accuracy. Using the software-provided classification, sensitivity and diagnostic accuracy were low for both the retinal nerve fiber layer and the GCC scans. FD-OCT does not seem to be decisive for early detection of structural damage in patients with no functional impairment. This suggests that there is a need for analysis software to be further refined to enhance glaucoma diagnostic capability.Keywords: OCT, RNFL, GCC, diagnostic accuracy 

  15. Peripheral nerve intramembranous particle density and distribution in chronic streptozotocin-induced diabetes in rats.

    Science.gov (United States)

    Gabriel, G; Thomas, P K; King, R H; Stolinski, C; Breathnach, A S

    1986-01-01

    Freeze-fracture studies have been made on the sciatic nerve of rats with chronic streptozotocin-induced diabetes mellitus. The density of intramembranous particles was reduced in both P and E faces of the axolemma of myelinated and unmyelinated axons, in myelin and in the perineurial cells. This may reflect a general reduction in protein synthesis, or excessive protein degradation, related to the diabetic state. The perineurial cells also showed gap junctions which are not normally present in adult rat peripheral nerve. These may represent a reaction to changes in perineurial activity consequent to alterations in the endoneurial tissue fluid. PMID:2950714

  16. Assessment of central chemosensitivity and cardiac sympathetic nerve activity using I-123 MIBG imaging in central sleep apnea syndrome in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Iodine-123 m-iodobenzylguanidine (MIBG) imaging has been used to study cardiac sympathetic function in various cardiac diseases. Central sleep apnea syndrome (CSAS) occurs frequently in patients with chronic heart failure (CHF) and is reported to be associated with a poor prognosis. One of the mechanisms of its poor prognosis may be related to impaired cardiac sympathetic activity. However, the relationship between chemosensitivity to carbon dioxide, which is reported to correlate with the severity of CSAS, and cardiac sympathetic activity has not been investigated. Therefore, this study was undertaken to assess cardiac sympathetic function and chemosensitivity to carbon dioxide in CHF patients. The oxygen desaturation index (ODI) was evaluated in 21 patients with dilated cardiomyopathy (male/female: 19/2, left ventricular ejection fraction (LVEF)5 times/h underwent polysomnography. Patients with an apnea hypopnea index >15/h but without evidence of obstructive apnea were defined as having CSAS. Early (15 min) and delayed (4 hr) planar MIBG images were obtained from these patients. The mean counts in the whole heart and the mediastinum were obtained. The heart-to-mediastinum count ratio of the delayed image (H/M) and the corrected myocardial washout rate (WR) were also calculated. The central chemoreflex was assessed with the rebreathing method using a hypercapnic gas mixture (7% CO2 and 93% O2). Ten of the and 93% O2). Ten of the 21 patients had CSAS. The H/M ratio was similar in patients both with and without CSAS (1.57±0.18 vs. 1.59±0.14, p=0.82). However, the WR was higher in patients with CSAS than in patients without CSAS (40±8% vs. 30±12%, p<0.05). ODI significantly correlated with central chemosensitivity to carbon dioxide. Moreover, there was a highly significant correlation between WR and central chemosensitivity (r=0.65, p<0.05). However, there was no correlation between ODI and the WR (r=0.36, p=0.11). Cardiac sympathetic nerve activity in patients with CHF and CSAS is impaired. However, central sleep apnea might not directly increase cardiac sympathetic nerve activity. We suggest that central chemosensitivity, which is considered to be one of the mechanisms of CSAS, is correlated with cardiac sympathetic nerve activity. (author)

  17. [Nerve repair strategies for restoration of erectile function after radical pelvic surgery].

    Science.gov (United States)

    May, F; Schoeler, S; Vroemen, M; Matiasek, K; Apprich, M; Erhardt, W; Hartung, R; Gansbacher, B; Weidner, N

    2005-07-01

    Iatrogenic cavernous nerve lesions occurring during radical pelvic surgery often lead to irreversible erectile dysfunction. The nerve defects after excision of the neurovascular bundles must be reconstructed by interposition grafting to supply a permissive scaffold for oriented axonal regrowth. The use of autologous nerve grafts for the repair of human cavernous nerves during radical prostatectomy has been controversial regarding the limited success achieved with bilateral nerve grafting. Artificial nerve guides consisting of natural or synthetic materials have been successfully used for bridging peripheral nerve defects. The combination with Schwann cells, neurotrophic factors and extracellular matrix components has been shown to promote cavernous nerve regeneration. PMID:15952015

  18. Histologic peripheral nerve changes in rats induced by deltamethrin.

    Science.gov (United States)

    Calore, E E; Cavaliere, M J; Puga, F R; Calore, N M; Rosa, A R; Weg, R; Dias, S S; Santos, R P

    2000-09-01

    Synthetic pyrethroid insecticides have been used in the last two decades largely because of their high activity as an insecticide and low mammalian toxicity. Some studies have demonstrated that these products, especially compounds with an alpha-cyano group, are toxic to the mammalian central nervous system (CNS) in acute intoxications. However, morphological studies are scarce. In the present work the histopathologic changes of the sciatic and tibial nerves of rats submitted to acute intoxication with the cyanopyrethroid deltamethrin were studied. For 3 consecutive days male Wistar rats received by oral gavage deltamethrin at a dose of 45 mg/kg body wt. On the 4th day fragments of sciatic and tibial nerves were studied by transmission electron microscopy (TEM) and teasing of individual nerve fibers. In addition, another group of rats were allowed to recover until the 10th day. Teasing of nerves of animals sacrificed on the 4th day revealed myelin ovoids, which are indicative of axonal damage. TEM demonstrated rare degenerated axons completely filled with organelles, in particular mitochondria, and with electron-dense lamellar bodies that resemble myelin figures. In addition, great cytoplasmic vacuolization caused by proliferation and dilation of the rough and smooth endoplasmic reticulum and Golgi apparatus was observed in some Schwann cells. No lesion was found 7 days after discontinuation of the treatment (group2). Since these histologic changes are transitory and scarce, the question arises: Are they related to the changes in NA(+), K(+)-ATPase activity or Na(+) channels caused by pyrethroid compounds? PMID:10993707

  19. Acetylcholinesterase activity and catecholamine content in thymic and splenic nerve fibres of white rats long after chronic exposure to physical factors and application of interleukin-1?

    International Nuclear Information System (INIS)

    Acetylcholinesterase (AChE) activity and catecholamine (CA) content in nerve fibres of the thymus and spleen of white rats were studied 6 months after prolonged combined exposure to ionizing radiation and heat and after application of interleukin-1? (IL-1?). Combined action of the physical factors induced a certain decrease in AChE activity and increase in CA content in both organs. Application of the cytokine to animals exposed to radiation and heat elicited a more pronounced decrease in AChE in these lymphoid organs and increase, especially in the spleen, in CA. The results suggest about enhanced responsiveness of the autonomic nervous system to IL-1? animals which had been long before exposed to prolonged combined action of radiation and heat

  20. Ocular nerve growth factor administration counteracts the impairment of neural precursor cell viability and differentiation in the brain subventricular area of rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Tirassa, Paola; Maccarone, Mattia; Carito, Valentina; De Nicolò, Sara; Fiore, Marco

    2015-05-01

    The ocular administration of nerve growth factor (NGF) as eye drops (oNGF) has been shown to exert protective effects in forebrain-injured animal models, including adult diabetes induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). This type 1 diabetes model was used in this study to investigate whether oNGF might extend its actions on neuronal precursors localised in the subventricular zone (SVZ). NGF or saline was administrated as eye drops twice daily for 2 weeks in rats with STZ-induced diabetes and healthy control rats. The expression of mature and precursor NGF and the NGF receptors, tropomyosin-related kinase A and neurotrophin receptor p75, and the levels of DNA fragmentation were analysed by ELISA and western blotting. Incorporation of bromodeoxyuridine was used to trace newly formed cells. Nestin, polysialylated neuronal cell adhesion molecule (PSA-NCAM), doublecortin (DCX) and glial fibrillary acidic protein antibodies were used to identify the SVZ cells by confocal microscopy. It was found that oNGF counteracts the STZ-induced cell death and the alteration of mature/pro-NGF expression in the SVZ. It also affects the survival and differentiation of SVZ progenitors. In particular, oNGF counteracts the reduction in the number of cells expressing PSA-NCAM/DCX (neuroblast type A cells) and the related reductions in the number and distribution of nestin/DCX-positive cells (C-type cells), or glia-committed cells (type B cells), observed in the SVZ of diabetic rats. These findings show that oNGF treatment counteracts the effect of type 1 diabetes on neuronal precursors in the SVZ, and further support the neuroprotective and reparative role of oNGF in the brain. PMID:25728260

  1. A Flat Interface Nerve Electrode With Integrated Multiplexer

    OpenAIRE

    Lertmanorat, Zeng; Montague, F. W.; Durand, Dominique M.

    2009-01-01

    One of the goals of peripheral nerve cuff electrode development is the design of an electrode capable of selectively activating a specific population of axons in a common nerve trunk. Several designs such as the round spiral electrode or the flat interface nerve electrode (FINE) have shown such ability. However, multiple contact electrodes require many leads, making the implantation difficult and potentially damaging to the nerve. Taking advantage of the flat geometry of the FINE, multiplexer...

  2. NF-?B Activation in T Helper 17 Cell Differentiation

    OpenAIRE

    Park, Sang-heon; Cho, Gabi; Park, Sung-gyoo

    2014-01-01

    CD28/T cell receptor ligation activates the NF-?B signaling cascade during CD4 T cell activation. NF-?B activation is required for cytokine gene expression and activated T cell survival and proliferation. Recently, many reports showed that NF-?B activation is also involved in T helper (Th) cell differentiation including Th17 cell differentiation. In this review, we discuss the current literature on NF-?B activation pathway and its effect on Th17 cell differentiation.

  3. Nerve lesioning with direct current

    Science.gov (United States)

    Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

    2011-02-01

    Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

  4. Optic Nerve Imaging

    Science.gov (United States)

    Optic Nerve Imaging email Send this article to a friend by filling out the fields below: Your name: ... Your eye doctor may use one of these optic nerve computer imaging techniques as part of your glaucoma ...

  5. Microvascular Cranial Nerve Palsy

    Science.gov (United States)

    ... Cranial Nerve Palsy? Tweet Microvascular cranial nerve palsy (MCNP) is a neurological condition involving the small blood ... affects the muscles that move the eyes. With MCNP, there is a blockage of blood flow to ...

  6. Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

    International Nuclear Information System (INIS)

    This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59±13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 ?g/kg/min before treatment. Patients were divided into good responders (LVEF increase ?15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with ?-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28±6 to 17±12 (p<0.05), H/M ratio increased from 1.79±0.26 to 2.07±0.32 (p<0.05), LVEF increased from 29±8% to 48±10% (p<0.01), and LVDd decreased from 65±4 mm to 58±5 mm ased from 65±4 mm to 58±5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

  7. Peripheral nerve injuries in the athlete.

    Science.gov (United States)

    Feinberg, J H; Nadler, S F; Krivickas, L S

    1997-12-01

    Peripheral nerves are susceptible to injury in the athlete because of the excessive physiological demands that are made on both the neurological structures and the soft tissues that protect them. The common mechanisms of injury are compression, traction, ischaemia and laceration. Seddon's original classification system for nerve injuries based on neurophysiological changes is the most widely used. Grade 1 nerve injury is a neuropraxic condition, grade 2 is axonal degeneration and grade 3 is nerve transection. Peripheral nerve injuries are more common in the upper extremities than the lower extremities, tend to be sport specific, and often have a biomechanical component. While the more acute and catastrophic neurological injuries are usually obvious, many remain subclinical and are not recognised before neurological damage is permanent. Early detection allows initiation of a proper rehabilitation programme and modification of biomechanics before the nerve injury becomes irreversible. Recognition of nerve injuries requires an understanding of peripheral neuroanatomy, knowledge of common sites of nerve injury and an awareness of the types of peripheral nerve injuries that are common and unique to each sport. The electrodiagnostic exam, usually referred to as the 'EMG', consists of nerve conduction studies and the needle electrode examination. It is used to determine the site and degree of neurological injury and to predict outcome. It should be performed by a neurologist or physiatrist (physician specialising in physical medicine and rehabilitation), trained and skilled in this procedure. Timing is essential if the study is to provide maximal information. Findings such as decreased recruitment after injury and conduction block at the site of injury may be apparent immediately after injury but other findings such as abnormal spontaneous activity may take several weeks to develop. The electrodiagnostic test assists with both diagnosis of the injury and in predicting outcome. Proximal nerve injuries have a poorer prognosis for neurological recovery. The most common peripheral nerve injury in the athlete is the burner syndrome. Though primarily a football injury, burners have been reported in wrestling, hockey, basketball and weight-lifting as a result of acute head, neck and/or shoulder trauma. Most burners are self-limiting, but they occasionally produce permanent neurological deficits. The axillary nerve is commonly injured with shoulder dislocations but is also susceptible to injury by direct compression. The sciatic and common peroneal nerves can be injured by trauma. The suprascapular, musculocutaneous, ulnar, median and tibial nerves are susceptible to entrapment. The long thoracic and femoral nerves can be injured by severe traction. PMID:9421863

  8. Peripheral Nerve Dysfunction Secondary to Lymphomatous Infiltration of the Nervous System by Non-Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Grimm S

    2014-01-01

    Full Text Available Lymphomatous meningitis (metastasis of lymphoma cells into the cerebrospinal-fluid spaces [CSF] and neurolymphomatosis (lymphomatous infiltration of a peripheral nerve or root are neurologic complications of non-Hodgkin?s lymphoma (NHL that frequently result in significant neurologic dysfunction. Leptomeningeal metastases most commonly present as cerebral dysfunction (hydrocephalus causing headache or apraxia of gait, encephalopathy, or seizures, cranial neuropathy (diplospia, facial weakness, vertigo, hearing loss, and tongue weakness, and spinal-nerve root dysfunction (incomplete cauda equina syndrome ? asymmetric lower- extremity weakness, sensory loss, or incontinence. Diagnosis is made by finding leptomeningeal enhancement on magnetic resonance imaging (MRI of the brain or spine or demonstration of lymphomatous cells by CSF cytology or flow cytometry. Treatment consists of focal radiotherapy for areas of bulky disease followed by intra-CSF chemotherapy or systemic chemotherapy. Neurolymphomatosis typically presents as a painful, sensorimotor peripheral neuropathy affecting multiple limbs in an asymmetric fashion with rapid evolution although variability in presentation can occur. Diagnosis is made by demonstration of enhancement of nerve roots on MRI of the brachial or lumbosacral plexus or peripheral nerves or by increased hyper-metabolic activity following the course of affected nerves on fluordeoxyglucose positron emission tomography (FDG-PET. Treatment of neurolymphomatosis consists of focal radiotherapy (if significant neurologic dysfunction is present and high-dose intravenous methotrexate therapy. Standard systemic chemotherapy agents are not effective since they do not penetrate the physiologic ?nerve-blood barrier?. Other disorders that must be differentiated from these entities include peripheral-nerve or nerve root compression and paraneoplastic neuropathy.

  9. Active lithium chloride cell for spacecraft power

    Science.gov (United States)

    Fleischmann, C. W.; Horning, R. J.

    1988-01-01

    An active thionyl chloride high rate battery is under development for spacecraft operations. It is a 540kC (150 Ah) battery capable of pulses up to 75A. This paper describes the design and initial test data on a 'state-of-the-art' cell that has been selected to be the baseline for the prototype cell for that battery. Initial data indicate that the specification can be met with fresh cells. Data for stored cells and additional environmental test data are in the process of being developed.

  10. The Physics of Nerves

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The accepted model for nerve pulse propagation in biological membranes seems insufficient. It is restricted to dissipative electrical phenomena and considers nerve pulses exclusively as a microscopic phenomenon. A simple thermodynamic model that is based on the macroscopic properties of membranes allows explaining more features of nerve pulse propagation including the phenomenon of anesthesia that has so far remained unexplained.

  11. Lactobacilli Differentially Activate Natural Killer Cells

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager

    Bacteria translocating across the gastrointestinal mucosa are presumed to gain access to NK cell compartments, as consumption of certain lactic acid bacteria has been shown to increase in vivo NK cytotoxicity. On-going research in our lab aims at describing strain-dependent effects of lactic acid bacteria on regulatory functions of NK-cells. Here, we have investigated how human gut flora-derived non-pathogenic lactobacilli affect NK cells in vitro, by measuring proliferation and IFN-gamma production of human peripheral blood NK cells upon bacterial stimulation. CD3-CD56+ NK cells were isolated from buffy coats by negative isolation using non-NK lineage specific antibodies and magnetic beads. NK cells were incubated with 10 microg/ml UV-inactivated bacteria for four days. Proliferation was assessed by incorporation of radioactive thymidine into NK cell DNA and cytokine concentrations were determined by ELISA. Co-incubation of NK cells and a Lactobacillus acidophilus strain caused increased proliferation of theNK cells and induced IFN-gamma production. The proliferative response was further enhanced in the presence of autologous monocytes, probably because cytokines, secreted by monocytes having engulfed bacteria, stimulated the growth of the NK cells. In contrast, a Lactobacillus paracasei strain caused the NK cells to proliferate only in the presence of monocytes. These results demonstrate that various lactobacilli have the capacity to activate NK cells in vitro, in a monocyte dependent or independent way. Such activation of NK cells may potentially skew an on-going or subsequent immune response towards a Th1 response.

  12. Carcinoma de células escamosas no olho de bovino com invasão cerebral através dos nervos cranianos Ocular squamous cell carcinoma in a cow with cerebral invasion through cranial nerves

    Directory of Open Access Journals (Sweden)

    Ricardo Rocha de Barros

    2006-10-01

    Full Text Available Um carcinoma de células escamosas foi removido do olho de uma vaca de 7 anos de idade que apresentava ptose da orelha esquerda, salivação e perda de peso progressiva. Devido ao mau prognóstico, a vaca foi submetida à eutanásia 9 meses após a cirurgia. Na necropsia e no exame histopatológico, foi observado que o tumor havia invadido o tronco encefálico através dos nervos cranianos. Outros achados de necropsia significativos incluíam pneumonia de aspiração e atrofia por desnervação do músculo temporal esquerdo.A squamous cell carcinoma of the eye was removed from a 7-year-old cow which presented drooping of left ear, drooling and progressive loss of weight. Due to poor prognosis it was euthanatized 9 months after surgery. At necropsy and histopathological examination it was found that the tumor had invaded the brain stem through the cranial nerves. Additional necropsy significant findings included aspiration pneumonia and denervation atrophy of the left temporal muscle.

  13. Comparative study of autologous stromal vascular fraction and adipose-derived stem cells for erectile function recovery in a rat model of cavernous nerve injury.

    Science.gov (United States)

    You, Dalsan; Jang, Myoung Jin; Kim, Bo Hyun; Song, Geehyun; Lee, Chunwoo; Suh, Nayoung; Jeong, In Gab; Ahn, Tai Young; Kim, Choung-Soo

    2015-04-01

    The abilities of intracavernous injection of autologous stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) to facilitate recovery of erectile function in a rat model of cavernous nerve (CN) injury were compared. Forty male Sprague-Dawley rats were randomly divided into four groups: sham and control groups (intracavernous injection of phosphate-buffered saline), SVF group (intracavernous injection of SVF), and ADSC group (intracavernous injection of ADSCs). Rats in the latter three groups underwent bilateral CN injury prior to injection. The evaluation of erectile function and histomorphometric studies were performed 4 weeks after injection. The ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (0.18 vs. 0.56, p erection in a rat model of CN injury. PMID:25792486

  14. Transplantation of muscle-derived stem cells plus biodegradable fibrin glue restores the urethral sphincter in a pudendal nerve-transected rat model

    Scientific Electronic Library Online (English)

    Y., Xu; Y.F., Song; Z.X., Lin.

    1076-10-01

    Full Text Available We investigated whether fibrin glue (FG) could promote urethral sphincter restoration in muscle-derived stem cell (MDSC)-based injection therapies in a pudendal nerve-transected (PNT) rat, which was used as a stress urinary incontinence (SUI) model. MDSCs were purified from the gastrocnemius muscles [...] of 4-week-old inbred female SPF Wistar rats and labeled with green fluorescent protein. Animals were divided into five groups (N = 15): sham (S), PNT (D), PNT+FG injection (F), PNT+MDSC injection (M), and PNT+MDSC+FG injection (FM). Each group was subdivided into 1- and 4-week groups. One and 4 weeks after injection into the proximal urethra, leak point pressure (LPP) was measured to assess urethral resistance function. Histology and immunohistochemistry were performed 4 weeks after injection. LPP was increased significantly in FM and M animals after implantation compared to group D (P

  15. Does nerve identification during open inguinal herniorrhaphy reduce the risk of nerve damage and persistent pain?

    DEFF Research Database (Denmark)

    Bischoff, J M; Aasvang, E K

    2012-01-01

    PURPOSE: Nerve identification during open inguinal hernia herniorrhaphy has been suggested as one of the factors that may reduce the risk of development of persistent postherniorrhaphy pain. In this prospective study, we evaluated whether intraoperative inguinal nerve identification influenced the risk of development of persistent postherniorrhaphy pain, sensory dysfunction in the groin and functional ability score after open hernia repair. METHODS: A total of 244 men with a primary inguinal hernia underwent open Lichtenstein repair in a high-volume hernia surgery centre, where information on inguinal nerve identification was registered during operation. Before the operation and 6 months postoperatively, functional pain-related impairment was assessed with Activities Assessment Scale and pain intensity scores with Numeric Rating Scale (NRS 0-10). Quantitative sensory testing in the groin was performed before operation and 6 months postoperatively, in order to investigate intraoperative inguinal nerve damage. RESULTS: The intraoperative nerve identification rates for the iliohypogastric, ilioinguinal and genitofemoral nerves were 94.7, 97.5 and 21.3 %, respectively. Thirty-nine patients (16.0 %) had substantial pain-related functional impairment at 6 months follow-up. There was no difference in risk of development of substantial pain-related functional impairment in patients with identification compared with non-identification of the iliohypogastric nerve (P = 1.0), the ilioinguinal nerve (P = 0.59), the genitofemoral nerve (P = 0.40) or all nerves (P = 0.52). There were no differences in regard to sensory loss in the groin area or in regard to improvement in functional outcome following surgery, between patients with and without nerve identification. CONCLUSIONS: Although intraoperative inguinal nerve identification should be aimed at, other factors may contribute to the risk of nerve damage and persistent pain after open groin hernia repair.

  16. Plasmin as a proinflammatory cell activator.

    Science.gov (United States)

    Syrovets, Tatiana; Lunov, Oleg; Simmet, Thomas

    2012-09-01

    The serine protease plasmin generated from its zymogen plasminogen is best known for its function as a key enzyme of the fibrinolytic cascade. However, beyond fibrinolysis, plasmin has a number of crucial functions in a variety of processes, including inflammation. Various cells can bind plasminogen and plasmin via plasminogen-binding sites exposing a C-terminal lysine. Plasmin, generated as a result of plasminogen activation at the cell surface, is protected from its physiological inhibitors. Apart from its ability to facilitate cell migration in tissues, plasmin is capable of triggering signaling, which depends on cellular binding via its lysine-binding sites and its proteolytic activity. Plasmin-induced signaling affects various functions of monocytes, macrophages, DCs, and others, with the list of affected cells still growing. In vitro and in vivo studies have demonstrated the ability of plasmin to stimulate the production of cytokines, ROS, and other mediators, thereby contributing to inflammation. Plasmin-induced chemotaxis of monocytes and DCs indicates that it is also a potent chemoattractant for immune cells. Therefore, excessive activation of plasmin in chronic inflammatory or autoimmune diseases might exacerbate the activation of inflammatory cells and the pathogenesis of the disease. This review focuses on the available evidence for physiological and pathophysiological roles the serine protease plasmin in inflammatory processes. PMID:22561604

  17. Enterocyte-afferent nerve interactions in dietary fat sensing.

    Science.gov (United States)

    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. PMID:25200298

  18. The role of exosomes in peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Rosanna C Ching

    2015-01-01

    Full Text Available Peripheral nerve injuries remain problematic to treat, with poor functional recovery commonly observed. Injuries resulting in a nerve gap create specific difficulties for axonal regeneration. Approaches to address these difficulties include autologous nerve grafts (which are currently the gold standard treatment and synthetic conduits, with the latter option being able to be impregnated with Schwann cells or stem cells which provide an appropriate micro-environment for neuronal regeneration to occur. Transplanting stem cells, however, infers additional risk of malignant transformation as well as manufacturing difficulties and ethical concerns, and the use of autologous nerve grafts and Schwann cells requires the sacrifice of a functioning nerve. A new approach utilizing exosomes, secreted extracellular vesicles, could avoid these complications. In this review, we summarize the current literature on exosomes, and suggest how they could help to improve axonal regeneration following peripheral nerve injury.

  19. Use of tubes in peripheral nerve repair.

    Science.gov (United States)

    Dahlin, L B; Lundborg, G

    2001-04-01

    The use of tubes as an alternative to primary nerve suture in fresh nerve transections has been introduced as a biologic approach to nerve injuries, creating optimal conditions for axonal regeneration over a short empty space intentionally created between the proximal and distal nerve ends. The idea may seem controversial and has been criticized using the arguments that silicone in itself may create problems like inflammation and the tube may compress the nerve ends. With the use of appropriately sized tubes for bridging a maximum 5-mm gap in human median and ulnar nerves, the authors have found the technique to be useful and persistent at follow-up examinations for up to 4 to 5 years. In addition, from the intellectual point of view, the principle illustrates the concept by which emphasis is placed on the intrinsic healing capacities of the nerve rather than on the technical skill of the surgeon. The thin mesothelial lining found around the silicone tube lacks primary inflammatory signs at follow-up after 1 year, and no signs of compression are seen. It may be an advantage because it allows sliding of the repair site against the surrounding tissues. Tubes made of bioresorbable material may seem ideal, but they may introduce new problems associated with the resorption process in terms of a substantial unrestricted macrophage invasion, fibrosis, and disorganized axonal growth. For an extended nerve defect, the use of autologous nerve grafts is still the gold standard, because no tubular conduit or other conduit has so far proved equal to autologous nerve grafts, at least not for reconstruction of human median and ulnar nerve trunks. Alternatives other than tubes are currently being developed and investigated. For the future, the use of tubes for repair and reconstruction of nerves may have interesting potentials, because such a structure allows several types of tissue engineering. Various matrices containing, for instance, appropriate cells, factors, or other stimulating agents can be introduced in the tube lumen and can also be incorporated in a slow-release form in the walls of the tube and manipulated. Cultured Schwann cells or other cellular components, with or without manipulated production machinery, are probably the cells of choice for introduction in the tubes. Tubes may thus prove to be interesting alternatives to conventional repair techniques for primary repair of nerves and for reconstruction of segmental defects and for neuroma treatment in the future. PMID:11525212

  20. Membrane targeting of p21-activated kinase 1 (PAK1) induces neurite outgrowth from PC12 cells.

    OpenAIRE

    Daniels, R H; Hall, P S; Bokoch, G. M.

    1998-01-01

    Rho-family GTPases regulate cytoskeletal dynamics in various cell types. p21-activated kinase 1 (PAK1) is one of the downstream effectors of Rac and Cdc42 which has been implicated as a mediator of polarized cytoskeletal changes in fibroblasts. We show here that the extension of neurites induced by nerve growth factor (NGF) in the neuronal cell line PC12 is inhibited by dominant-negative Rac2 and Cdc42, indicating that these GTPases are required components of the NGF signaling pathway. While ...

  1. Processes of excitation in the dendrites and in the soma of single isolated sensory nerve cells of the lobster and crayfish.

    Science.gov (United States)

    EYZAGUIRRE, C; KUFFLER, S W

    1955-09-20

    The stretch receptor organs of Alexandrowicz in lobster and crayfish possess sensory neurons which have their cell bodies in the periphery. The cell bodies send dendrites into a fine nearby muscle strand and at the opposite pole they give rise to an axon running to the central nervous system. Mechanisms of excitation between dendrites, cell soma, and axon have been studied in completely isolated receptor structures with the cell components under visual observation. Two sensory neuron types were investigated, those which adapt rapidly to stretch, the fast cells, and those which adapt slowly, the slow cells. 1. Potentials recorded from the cell body of the neurons with intracellular leads gave resting potentials of 70 to 80 mv. and action potentials which in fresh preparations exceeded the resting potentials by about 10 to 20 mv. In some experiments chymotrypsin or trypsin was used to make cell impalement easier. They did not appreciably alter resting or action potentials. 2. It has been shown that normally excitation starts in the distal portion of dendrites which are depolarized by stretch deformation. The changed potential within the dendritic terminals can persist for the duration of stretch and is called the generator potential. Secondarily, by electrotonic spread, the generator potential reduces the resting potential of the nearby cell soma. This excitation spread between dendrites and soma is seen best during subthreshold excitation by relatively small stretches of normal cells. It is also seen during the whole range of receptor stretch in neurons in which nerve conduction has been blocked by an anesthetic. The electrotonic changes in the cells are graded, reflecting the magnitude and rate of rise of stretch, and presumably the changing levels of the generator potential. Thus in the present neurons the resting potential and the excitability level of the cell soma can be set and controlled over a wide range by local events within the dendrites. 3. Whenever stretch reduces the resting membrane potential, measured in the relaxed state in the cell body, by 8 to 12 mv. in slow cells and by 17 to 22 mv. in fast cells, conducted impulses are initiated. It is thought that in slow cells conducted impulses are initiated in the dendrites while in fast cells they arise in the cell body or near to it. In fresh preparations the speed of stretch does not appreciably influence the membrane threshold for discharges, while during developing fatigue the firing level is higher when extension is gradual. 4. Some of the specific neuron characteristics are: Fast receptor cells have a relatively high threshold to stretch. During prolonged stretch the depolarization of the cell soma is not well maintained, presumably due to a decline in the generator potential, resulting in cessation of discharges in less than a minute. This appears to be the basis of the relatively rapid adaptation. A residual subthreshold depolarization can persist for many minutes of stretch. Slow cells which resemble the sensory fibers of vertebrate spindles are excited by weak stretch. Their discharge rate remains remarkably constant for long periods. It is concluded that, once threshold excitation is reached, the generator potential within slow cell dendrites is well maintained for the duration of stretch. Possible reasons for differences in discharge properties between fast and slow cells are discussed. 5. If stretch of receptor cells is gradually continued above threshold, the discharge frequency first increases over a considerable range without an appreciable change in the firing level for discharges. Beyond that range the membrane threshold for conducted responses of the cell soma rises, the impulses become smaller, and partial conduction in the soma-axon boundary region occurs. At a critical depolarization level which may be maintained for many minutes, all conduction ceases. These overstretch phenomena are reversible and resemble cathodal block. 6. The following general scheme of excitation is proposed: stretch deformation of dendritic terminals --> generator

  2. Autonomic nerves in pulmonary veins

    OpenAIRE

    Tan, Alex Y; CHEN, PENG-SHENG; Chen, Lan S; Fishbein, Michael C

    2006-01-01

    Rapid repetitive activities arising from pulmonary veins may initiate atrial fibrillation. The basis of these rapid repetitive activities remains unclear, but recent evidence suggests that the autonomic nervous system plays an important role in their formation. Pulmonary veins and the adjoining left atrium are highly innervated structures. This review summarizes recent developments in the understanding of the anatomy of autonomic nerves in and around pulmonary veins and their implications for...

  3. Techniques of facial nerve block.

    OpenAIRE

    Schimek, F.; Fahle, M.

    1995-01-01

    The efficacy of different techniques of facial nerve block for cataract surgery was investigated. Forty four patients underwent either modified O'Brien, Atkinson, van Lint, or lid blocks. Intentional muscle activity of the orbicularis oculi muscle was recorded and the area under the EMG curve calculated for quantitative comparison of muscle activity between the groups before and after injection of lignocaine with the vasoconstrictor naphazoline nitrate. In addition, the force of lid closure w...

  4. Cerebellar Purkinje cell activity drives motor learning

    OpenAIRE

    Nguyen-vu, T. D. Barbara; Kimpo, Rhea R.; Rinaldi, Jacob M.; Kohli, Arunima; Zeng, Hongkui; Deisseroth, Karl; Raymond, Jennifer L.

    2013-01-01

    The climbing fiber input to the cerebellar cortex is thought to provide instructive signals that drive the induction of motor skill learning. We found that optogenetic activation of Purkinje cells, the sole output neurons of the cerebellar cortex, can also drive motor learning in mice. This dual control over the induction of learning by climbing fibers and Purkinje cells can expand the learning capacity of motor circuits.

  5. Effects of Comb Tooth Cap Medicinal Mushroom, Hericium ramosum (Higher Basidiomycetes) Mycelia on DPPH Radical Scavenging Activity and Nerve Growth Factor Synthesis.

    Science.gov (United States)

    Suruga, Kohei; Kadokura, Kazunari; Sekino, Yoshihiro; Nakano, Takafumi; Matsuo, Koichi; Irie, Keiichi; Mishima, Kenichi; Yoneyama, Makoto; Komatsu, Yasuhiro

    2015-01-01

    The goal of this study was to evaluate the antioxidant effects of and nerve growth factor (NGF) synthesis caused by Hericium ramosum mycelia. Wild mushroom fruiting bodies were collected from nature to isolate their mycelia. Pieces of H. ramosum fruiting bodies were plated onto 90-mm Petri dishes with potato dextrose agar medium to isolate their mycelia. Antioxidant activity was measured using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activity in vitro; the ethanol extract from H. ramosum mycelia (63.11 µmol Trolox/g) was more potent than that of other mushroom mycelia extracts. There was a proportional relationship (R2 = 0.7929) between DPPH radical scavenging activity and total phenolic content in extracts of different mushroom mycelia. We investigated the ability of H. ramosum mycelia to inducing NGF synthesis in vivo. Oral administration of H. ramosum mycelia significantly increased concentrations of NGF in the hippocampus of intact mice. These results are the first concerning antioxidant activity and NGF synthesis of H. ramosum mycelia. These mushroom mycelia could be useful as food and/or nutritional supplements because of certain biological functions. PMID:25954959

  6. Ontogenic development of nerve fibers in human fetal livers: an immunohistochemical study using neural cell adhesion molecule (NCAM) and neuron-specific enolase (NSE).

    Science.gov (United States)

    Terada, Tadashi

    2015-04-01

    The aim of the study was to investigate nerve fibers (NF) in human fetal livers. An immunohistochemical study was performed. NF were classified into portal tract innervation (PoI) and parenchymal innervation (PaI). The hilum area showed many Pol NF at 7 GW, and NF increased with gestational week (GW). Direct innervations to biliary epithelium were recognized. In large portal tracts, a few NCAM-positive mesenchymal cells were seen at 8 GW and many mesenchymal cells were noted around 12 GW. Apparent NF emerged around 15 GW, and NF increased with GW. Many NF plexuses were seen in 30-40 GW. In small portal tracts, no NF were seen in 7-10 GW. A few NCAM-positive mesenchymal cells emerged in 11 GW, and they increased thereafter. Apparent NF were seen around 20 GW and NF increased with GW. At term (40 GW), PoI NF were still immature. Ductal plate (DP) was positive for NCAM, NSE, chromogranin and synaptophysin, and direct innervations to DP were seen. The direct innervations to developing bile ducts and peribiliary glands were also seen. PaI NF were first seen at 21 GW and was consistent until 40 GW in which a few NF were seen in PaI. These observations suggest that PoI NF arise from committed portal mesenchyme. PaI NF are very immature at 40 GW. There are direct innervations to bile ducts, peribiliary glands, portal veins, hepatic arteries, and DP. PMID:25326085

  7. Retinal nerve fiber layer and ganglion cell complex thickness assessment in patients with Alzheimer disease and mild cognitive impairment. Preliminary results

    Directory of Open Access Journals (Sweden)

    A. S. Tiganov

    2014-07-01

    Full Text Available Purpose: to investigate the retinal nerve fiber layer (RNFL and the macular ganglion cell complex (GCC in patients with Alzheimer`s disease and mild cognitive impairment.Methods: this study included 10 patients (20 eyes with Alzheimer`s disease, 10 patients with mild cognitive impairment and 10 age- and sex-matched healthy controls that had no history of dementia. All the subjects underwent psychiatric examination, including the Mini-Mental State Examination (MMSE, and complete ophthalmological examination, comprising optical coherence tomography and scanning laser polarimetry.Results: there was a significant decrease in GCC thickness in patients with Alzheimer`s disease compared to the control group, global loss volume of ganglion cells was higher than in control group. there was no significant difference among the groups in terms of RNFL thickness. Weak positive correlation of GCC thickness and MMSE results was observed.Conclusion: Our data confirm the retinal involvement in Alzheimer`s disease, as reflected by loss of ganglion cells. Further studies will clear up the role and contribution of dementia in pathogenesis of optic neuropathy.

  8. Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine

    OpenAIRE

    Zhuang, Zhi-Ye; Kawasaki, Yasuhiko; Tan, Ping-Heng; Wen, Yeong-Ray; Huang, Jing; Ji, Ru-Rong

    2006-01-01

    Accumulating evidence suggests that microglial cells in the spinal cord play an important role in the development of neuropathic pain. However, it remains largely unknown how glia interact with neurons in the spinal cord after peripheral nerve injury. Recent studies suggest that the chemokine fractalkine may mediate neural/microglial interaction via its sole receptor CX3CR1. We have examined how fractalkine activates microglia in a neuropathic pain condition produced by spinal nerve ligation ...

  9. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Directory of Open Access Journals (Sweden)

    Jasmin Luc

    2010-12-01

    Full Text Available Abstract Background Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS. Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. Results CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. Conclusions Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

  10. Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

    Science.gov (United States)

    Murashov, A. K.; Ul Haq, I.; Hill, C.; Park, E.; Smith, M.; Wang, X.; Wang, X.; Goldberg, D. J.; Wolgemuth, D. J.

    2001-01-01

    The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

  11. PACAP interacts with PAC1 receptors to induce tissue plasminogen activator (tPA) expression and activity in schwann cell-like cultures.

    Science.gov (United States)

    Castorina, Alessandro; Waschek, James A; Marzagalli, Rubina; Cardile, Venera; Drago, Filippo

    2015-01-01

    Regeneration of peripheral nerves depends on the abilities of rejuvenating axons to migrate at the injury site through cellular debris and altered extracellular matrix, and then grow along the residual distal nerve sheath conduit and reinnervate synaptic targets. Considerable evidence suggest that glial cells participate in this process, although the mechanisms remain to be clarified. In cell culture, regenerating neurites secrete PACAP, a peptide shown to induce the expression of the protease tissue plasminogen activator (tPA) in neural cell types. In the present studies, we tested the hypothesis that PACAP can stimulate peripheral glial cells to produce tPA. More specifically, we addressed whether or not PACAP promoted the expression and activity of tPA in the Schwann cell line RT4-D6P2T, which shares biochemical and physical properties with Schwann cells. We found that PACAP dose- and time-dependently stimulated tPA expression both at the mRNA and protein level. Such effect was mimicked by maxadilan, a potent PAC1 receptor agonist, but not by the PACAP-related homolog VIP, suggesting a PAC1-mediated function. These actions appeared to be mediated at least in part by the Akt/CREB signaling cascade because wortmannin, a PI3K inhibitor, prevented peptide-driven CREB phosphorylation and tPA increase. Interestingly, treatment with BDNF mimicked PACAP actions on tPA, but acted through both the Akt and MAPK signaling pathways, while causing a robust increase in PACAP and PAC1 expression. PACAP6-38 totally blocked PACAP-driven tPA expression and in part hampered BDNF-mediated effects. We conclude that PACAP, acting through PAC1 receptors, stimulates tPA expression and activity in a Akt/CREB-dependent manner to promote proteolytic activity in Schwann-cell like cultures. PMID:25658447

  12. Knockdown of Dock7 in vivo specifically affects myelination by Schwann cells and increases myelin thickness in sciatic nerves without affecting axon thickness

    Directory of Open Access Journals (Sweden)

    Kazuaki Nakamura

    2012-07-01

    Full Text Available During development of the peripheral nervous system (PNS, Schwann cells (SCs wrap individual axons to form myelin sheaths, which act as surrounding insulators and markedly enhance the propagation of the action potential. In peripheral neuropathies such as Guillain-Barré syndrome (GBS and inherited demyelinating Charcot-Marie-Tooth (CMT disease and diabetic neuropathies, chronic demyelination and defective remyelination are repeated, causing more severe neuropathies. It is thus thought that development of a drug that promotes proper myelination with minimal side effects could provide an effective therapy for these diseases. As yet, however, little is known about therapeutic target molecules and genetically-modified mice for testing such approaches. We previously cloned the dock7 gene and characterized Dock7 as the regulator controlling SC myelination; however, an important issue, whether knockdown of Dock7 specifically affects myelination by SCs but not leaves neurons unaffected, has remained unclear. Here, we generate newly-produced transgenic mice harboring short-hairpin RNA (shRNA targeting Dock7. We also describe that Dock7 shRNA transgenic mice exhibit enhanced myelin thickness without affecting axon thickness in sciatic nerves of the PNS, as reduced thickness of the axon diameter is the primary indicator of denatured neurons. Similarly, purified in vitro SC-neuronal cocultures established from transgenic mice exhibit enhanced formation of myelin segments, suggesting that knockdown of Dock7 promotes myelination by SCs. Collectively, Dock7 knockdown specifically affects SC myelination in sciatic nerves, providing evidence that Dock7 may be a promising drug-target-specific molecules for developing a therapy for peripheral neuropathies that aims to enhance myeliantion.

  13. Imaging the trigeminal nerve

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093, Lisboa (Portugal)], E-mail: borgalexandra@gmail.com; Casselman, Jan [Department of Radiology, A. Z. St Jan Brugge and A. Z. St Augustinus Antwerpen Hospitals (Belgium)

    2010-05-15

    Of all cranial nerves, the trigeminal nerve is the largest and the most widely distributed in the supra-hyoid neck. It provides sensory input from the face and motor innervation to the muscles of mastication. In order to adequately image the full course of the trigeminal nerve and its main branches a detailed knowledge of neuroanatomy and imaging technique is required. Although the main trunk of the trigeminal nerve is consistently seen on conventional brain studies, high-resolution tailored imaging is mandatory to depict smaller nerve branches and subtle pathologic processes. Increasing developments in imaging technique made possible isotropic sub-milimetric images and curved reconstructions of cranial nerves and their branches and led to an increasing recognition of symptomatic trigeminal neuropathies. Whereas MRI has a higher diagnostic yield in patients with trigeminal neuropathy, CT is still required to demonstrate the bony anatomy of the skull base and is the modality of choice in the context of traumatic injury to the nerve. Imaging of the trigeminal nerve is particularly cumbersome as its long course from the brainstem nuclei to the peripheral branches and its rich anastomotic network impede, in most cases, a topographic approach. Therefore, except in cases of classic trigeminal neuralgia, in which imaging studies can be tailored to the root entry zone, the full course of the trigeminal nerve has to be imaged. This article provides an update in the most recent advances on MR imaging technique and a segmental imaging approach to the most common pathologic processes affecting the trigeminal nerve.

  14. Electrochemical cell having improved active life

    Energy Technology Data Exchange (ETDEWEB)

    Doddapaneni, N.

    1987-10-06

    In an electrochemical cell having an active metal anode, an electrolyte solution is described comprising an oxychloride solvent depolarizer containing a metal salt of the anode and a cathode. The improvement comprises an amount of additive in the electrolyte selected from the group consisting of CoTCPP and CoTCPC and mixtures thereof.

  15. US and MR imaging of peripheral nerves in leprosy

    International Nuclear Information System (INIS)

    Objective. To analyze peripheral nerves with ultrasonography (US) and magnetic resonance imaging (MR) in leprosy and assess the role of imaging in leprosy patients. Results. Leprosy nerves were classified into three groups based on imaging appearance: group I consisted of 17 normal-appearing nerves; group II, of 30 enlarged nerves with fascicular abnormalities; group III, of 11 nerves with absent fascicular structure. Group II nerves were from patients subjected to reversal reactions; 75% of patients with group III nerves had a history of erythema nodosum leprosum. Nerve compression in osteofibrous tunnels was identified in 33% of group II and 18% of group III nerves. Doppler US and MR imaging were 74% and 92% sensitive in identifying active reactions, based on detection of endoneural color flow signals, long T2 and Gd enhancement. In 64% of cases, follow-up studies showed decreased color flow and Gd uptake after steroids and decompressive surgery.Conclusions. US and MR imaging are able to detect nerves abnormalities in leprosy. Active reversal reactions are indicated by endoneural color flow signals as well as by an increased T2 signal and Gd enhancement. These signs would suggest rapid progression of nerve damage and a poor prognosis unless antireactional treatment is started. (orig.)

  16. US and MR imaging of peripheral nerves in leprosy

    Energy Technology Data Exchange (ETDEWEB)

    Martinoli, C. [Department of Radiology ' ' R' ' , DICMI, University of Genoa, Genoa (Italy); Cattedra di Radiologia ' ' R' ' , Universita di Genova, Largo Rosanna Benzi, 8, I-16132 Genoa (Italy); Derchi, L.E.; Gandolfo, N. [Department of Radiology ' ' R' ' , DICMI, University of Genoa, Genoa (Italy); Bertolotto, M. [Department of Radiology, University of Trieste, Strada di Fiume, I-34149 Trieste (Italy); Bianchi, S. [Division de Radiodiagnostic. Hopital Cantonal Huniversitaire, Rue Micheli du Crest, Geneva (Switzerland); Fiallo, P.; Nunzi, E. [Department of Tropical Medicine, University of Genoa, Largo Rosanna Benzi 8, I-16132 Genoa (Italy)

    2000-03-30

    Objective. To analyze peripheral nerves with ultrasonography (US) and magnetic resonance imaging (MR) in leprosy and assess the role of imaging in leprosy patients. Results. Leprosy nerves were classified into three groups based on imaging appearance: group I consisted of 17 normal-appearing nerves; group II, of 30 enlarged nerves with fascicular abnormalities; group III, of 11 nerves with absent fascicular structure. Group II nerves were from patients subjected to reversal reactions; 75% of patients with group III nerves had a history of erythema nodosum leprosum. Nerve compression in osteofibrous tunnels was identified in 33% of group II and 18% of group III nerves. Doppler US and MR imaging were 74% and 92% sensitive in identifying active reactions, based on detection of endoneural color flow signals, long T2 and Gd enhancement. In 64% of cases, follow-up studies showed decreased color flow and Gd uptake after steroids and decompressive surgery.Conclusions. US and MR imaging are able to detect nerves abnormalities in leprosy. Active reversal reactions are indicated by endoneural color flow signals as well as by an increased T2 signal and Gd enhancement. These signs would suggest rapid progression of nerve damage and a poor prognosis unless antireactional treatment is started. (orig.)

  17. Facial Nerve Neuroma Management

    OpenAIRE

    Weber, Peter C.; Osguthorpe, J. David

    1998-01-01

    Three facial nerve neuromas were identified in the academic year 1994-1995. Each case illustrates different management dilemmas. One patient with a grade III facial nerve palsy had a small geniculate ganglion neuroma with the dilemma of decompression versus resection clear nerve section margins. The second patient underwent facial neuroma resection with cable graft reconstruction, but the permanent sections were positive. The last patient had a massive neuroma in which grafting versus other f...

  18. Engineering Peripheral Nerve Repair

    OpenAIRE

    Marquardt, Laura; Sakiyama-Elbert, Shelly E

    2013-01-01

    Current approaches for treating peripheral nerve injury have resulted in promising, yet insufficient functional recovery compared to the clinical standard of care, autologous nerve grafts. In order to design a construct that can match the regenerative potential of the autograft, all facets of nerve tissue must be incorporated in a combinatorial therapy. Engineered biomaterial scaffolds in the future will have to promote enhanced regeneration and appropriate reinnervation by targeting the high...

  19. Long pacing Pulses Reduce Phrenic Nerve Stimulation in Left Ventricular Pacing

    DEFF Research Database (Denmark)

    HjortshØj, SØren; Heath, Finn Peter

    2014-01-01

    Phrenic nerve stimulation is a major obstacle in cardiac resynchronization therapy (CRT). Activation characteristics of the heart and phrenic nerve are different with higher chronaxie for the heart. Therefore, longer pulse durations could be beneficial in preventing phrenic nerve stimulation during CRT due to a decreased threshold for the heart compared to the phrenic nerve. We investigated if long pulse durations decreased left ventricular (LV) thresholds relatively to phrenic nerve thresholds in humans.

  20. Changes in calcineurin message, enzyme activity and protein content in the spinal dorsal horn are associated with chronic constriction injury of the rat sciatic nerve.

    Science.gov (United States)

    Miletic, G; Sullivan, K M; Dodson, A M K; Lippitt, J A; Schneider, J A; Miletic, V

    2011-08-11

    Plasticity in the spinal dorsal horn is thought to underlie the development of neuropathic pain. Calcineurin (protein phosphatase 3) plays an important role in plasticity in the brain. Here we examined whether chronic constriction injury (CCI) of the sciatic nerve modifies calcineurin expression in the spinal dorsal horn. Male rats were assigned to control (uninjured), sham-operated or CCI groups. CCI animals exhibited both a shift in weight bearing and a reduction in paw withdrawal latencies as signs of pain behavior. At 3 days (3D) the pain behavior was associated with a significant increase in calcineurin gene expression, enzyme activity and content of its A? isoform in the ipsilateral spinal dorsal horn. In contrast, while the pain behavior persisted at 7 days (7D) calcineurin gene expression returned to control levels and activity and protein content decreased. A single intrathecal injection of MK-801 15 min before the ligation attenuated both signs of pain behavior in 3D but not 7D CCI animals. The same pre-treatment also prevented the CCI-associated increases in calcineurin in these animals. These data suggested an involvement of calcineurin in CCI-elicited neuropathic pain. The time-dependent divergent changes in calcineurin expression may underlie the different phases of neuropathic pain development. PMID:21596102

  1. Usefulness of biventricular pacing to improve cardiac symptoms, exercise capacity and sympathetic nerve activity in patients with moderate to severe chronic heart failure

    International Nuclear Information System (INIS)

    Although cardiac resynchronization using biventricular pacing (BVP) results in significant clinical improvement in patients with chronic heart failure (CHF), there is no evidence of improvement in sympathetic nerve activity (SNA). Eighteen patients with CHF (dilated cardiomyopathy/ischemic cardiomyopathy=14/4) and left ventricular (LV) ejection fraction 160 ms and dyssynchronous LV wall motion were classified into 2 groups based on the findings of 99mTc-methoxyisobutyl isonitrile (MIBI) quantitative gated single-photon emission computed tomography (SPECT) (QGS). Resynchronization was considered to be present when the difference between the QGS frame number for end-systole for the LV septal and lateral walls (dyssynchrony index) disappeared. Group A achieved resynchronization after BVP, but not Group B. In group A, New York Heart Association functional class (p=0.0002), specific activity scale (p=0.0001), total defect score (p123I-metaiodobenzylguanidine imaging (p<0.05) were significantly improved after resynchronization. However, there was no significant change in group B. Cardiac resynchronization after BVP can improve cardiac symptoms, exercise capacity, and SNA in patients with moderate to severe CHF. (author)

  2. Glucose activates prenyltransferases in pancreatic islet ?-cells

    International Nuclear Information System (INIS)

    A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet ?-cell. These signaling proteins undergo post-translational modifications [e.g., prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretory granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological insulin secretogues [e.g., glucose] has not been investigated thus far. Herein, we report immunological localization, sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 ?-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the ?-subunits of FTase/GGTase-1, but not the ?-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets. Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin.

  3. Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

    Science.gov (United States)

    Salton, S R; Fischberg, D J; Dong, K W

    1991-01-01

    Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified. Images PMID:2017159

  4. Quantitative assessment of optic nerve head pallor

    International Nuclear Information System (INIS)

    Ischaemia, loss of neural tissue, glial cell activation and tissue remodelling are symptoms of anterior ischaemic as well as glaucomatous optic neuropathy leading to pallor of the optic nerve head. Here, we describe a simple method for the pallor measurement using a fundus camera equipped with a colour CCD camera and a special dual bandpass filter. The reproducibility of the determined mean pallor value was 11.7% (coefficient of variation for repeated measurements in the same subject); the variation over six healthy subjects was 14.8%. A significant difference between the mean pallor of an atrophic disc and that of the contralateral eye of the same individual was found. However, even the clinically unaffected eye showed a significantly increased pallor compared to the mean of the healthy control group. Thus, optic disc pallor measurement, as described here, may be helpful in the early detection and follow-up of optic neuropathy

  5. Nerve repair: toward a sutureless approach.

    Science.gov (United States)

    Barton, Matthew J; Morley, John W; Stoodley, Marcus A; Lauto, Antonio; Mahns, David A

    2014-10-01

    Peripheral nerve repair for complete section injuries employ reconstructive techniques that invariably require sutures in their application. Sutures are unable to seal the nerve, thus incapable of preventing leakage of important intraneural fluids from the regenerating nerve. Furthermore, sutures are technically demanding to apply for direct repairs and often induce detrimental scarring that impedes healing and functional recovery. To overcome these limitations, biocompatible and biodegradable glues have been used to seal and repair peripheral nerves. Although creating a sufficient seal, they can lack flexibility and present infection risks or cytotoxicity. Other adhesive biomaterials have recently emerged into practice that are usually based on proteins such as albumin and collagen or polysaccharides like chitosan. These adhesives form their union to nerve tissue by either photothermal (tissue welding) or photochemical (tissue bonding) activation with laser light. These biomaterial adhesives offer significant advantages over sutures, such as their capacity to unite and seal the epineurium, ease of application, reduced invasiveness and add the potential for drug delivery in situ to facilitate regeneration. This paper reviews a number of different peripheral nerve repair (or reconstructive) techniques currently used clinically and in experimental procedures for nerve injuries with or without tissue deficit. PMID:25015388

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

    Directory of Open Access Journals (Sweden)

    Aoki Junken

    2010-11-01

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

  7. Silk Fibroin Conduits: A Cellular and Functional Assessment of Peripheral Nerve Repair

    OpenAIRE

    Ghaznavi, Amir Mahan; Kokai, Lauren E.; Lovett, Michael L.; Kaplan, David L.; Marra, Kacey G

    2011-01-01

    Novel silk fibroin conduits were designed with appropriate porosity for peripheral nerve repair. The aim of this work was to utilize these conduits to examine cell inflammatory responses and functional recovery in a sciatic nerve defect model.

  8. Nerve Disease and Bladder Control

    Science.gov (United States)

    ... Disease and Bladder Control Nerve Disease and Bladder Control On this page: What bladder control problems does ... bladder do not work properly. [ Top ] What bladder control problems does nerve damage cause? Nerves that work ...

  9. IMMUNOMODULATORY ACTIVITY OF MESENCHIMAL STROMAL (STEM CELLS

    Directory of Open Access Journals (Sweden)

    V. B. Klimovich

    2014-08-01

    Full Text Available Mesenchymal stromal or stem cells (MSC represent a population of primitive fibroblastlike cells that are able to differentiate into cellular lineages of connective tissue (osteocytes, chondrocytes, adipocytes, skeletal muscles, and blood vessels. The review deals with contemporary views concerning descent, immunophenotype and immunogenicity of MSC. The studies over last decade revealed an ability of MSC to function as immunomodulatory populations which may suppress innate immunity factors (dendritic cells, natural killers, complement, as well as T-helpers and cytotoxic T-lymphocytes, along with activation of regulatory T lymphocytes (Treg. Special attention is given to analysis of conflicting data about influence of MSC on functions of B-lymphocytes and plasma cells in experimental settings, both in vitro and in vivo conditions. Data presently available are insufficient to explain the controversions revealed. In future investigations, it is necessary to consider attribution of B-cells to B1a, B1b, or B2 subpopulations as well as possible presence of poorly studied regulatory B-cells. It is also important also to take into account potential heterogeneity of initial MSC populations being isolated according to previously approved protocols. (Med. Immunol., 2014, vol. 16, N 2, pp 107-126

  10. The effects of dietary treatment with essential fatty acids on sciatic nerve conduction and activity of the Na+/K+ pump in streptozotocin-diabetic rats.

    OpenAIRE

    Lockett, M. J.; Tomlinson, D. R.

    1992-01-01

    1. This study examined the effects of dietary essential fatty acid supplementation (5% (w/w) evening primrose oil) upon sciatic motor nerve conduction velocity and 86Rb+ pumping in sciatic nerve endoneurial preparations in rats with 4 to 5 weeks of streptozotocin-induced diabetes. 2. Control diabetic rats (dietary supplementation with 5% (w/w) hydrogenated coconut oil) exhibited a reduction in motor nerve conduction velocity (16%; P less than 0.05) compared to similarly-fed non-diabetic contr...

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

    Science.gov (United States)

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

    2013-02-01

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

  12. Transforming growth factor ? isoforms in human optic nerve heads

    OpenAIRE

    Pena, J. (collab.); TAYLOR, A; Ricard, C.; Vidal, I.; Hernandez, M.

    1999-01-01

    AIM—To determine if the isoforms of transforming growth factor ? (TGF-?) are present in fetal, normal adult, and glaucomatous optic nerve heads.?METHODS—To localise cells synthesising TGF-?, optic nerve heads were stained using antibodies to TGF-?1, TGF-?2, and TGF-?3. To demonstrate synthesis, human optic nerve heads from fetal, glaucomatous, and normal age matched subjects were explanted, cultured overnight, and the culture supernatant was assayed for the presence of TGF-?1 and TGF-?2 by bi...

  13. Polymer scaffolds with preferential parallel grooves enhance nerve regeneration.

    Science.gov (United States)

    Mobasseri, Atefeh; Faroni, Alessandro; Minogue, Ben M; Downes, Sandra; Terenghi, Giorgio; Reid, Adam J

    2015-03-01

    We have modified the surface topography of poly ?-caprolactone (PCL) and polylactic acid (PLA) blended films to improve cell proliferation and to guide the regeneration of peripheral nerves. Films with differing shaped grooves were made using patterned silicon templates, sloped walls (SL), V-shaped (V), and square-shaped (SQ), and compared with nongrooved surfaces with micropits. The solvent cast films were tested in vitro using adult adipose-derived stem cells differentiated to Schwann cell-like cells. Cell attachment, proliferation, and cell orientation were all improved on the grooved surfaces, with SL grooves giving the best results. We present in vivo data on Sprague-Dawley rat sciatic nerve injury with a 10-mm gap, evaluating nerve regeneration at 3 weeks across a polymer nerve conduit modified with intraluminal grooves (SL, V, and SQ) and differing wall thicknesses (70, 100, 120, and 210??m). The SL-grooved nerve conduit showed a significant improvement over the other topographical-shaped grooves, while increasing the conduit wall thickness saw no positive effect on the biological response of the regenerating nerve. Furthermore, the preferred SL-grooved conduit (C) with 70??m wall thickness was compared with the current clinical gold standard of autologous nerve graft (Ag) in the rat 10-mm sciatic nerve gap model. At 3 weeks postsurgery, all nerve gaps across both groups were bridged with regenerated nerve fibers. At 16 weeks, features of regenerated axons were comparable between the autograft (Ag) and conduit (C) groups. End organ assessments of muscle weight, electromyography, and skin reinnervation were also similar between the groups. The comparable experimental outcome between conduit and autograft, suggests that the PCL/PLA conduit with inner lumen microstructured grooves could be used as a potential alternative treatment for peripheral nerve repair. PMID:25435096

  14. A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells

    International Nuclear Information System (INIS)

    Spinal muscular atrophy (SMA) is caused by reduced levels of SMN (survival of motor neurons protein) and consequent loss of motor neurons. SMN is involved in snRNP transport and nuclear RNA splicing, but axonal transport of SMN has also been shown to occur in motor neurons. SMN also binds to the small actin-binding protein, profilin. We now show that SMN and profilin II co-localise in the cytoplasm of differentiating rat PC12 cells and in neurite-like extensions, especially at their growth cones. Many components of known SMN complexes were also found in these extensions, including gemin2 (SIP-1), gemin6, gemin7 and unrip (unr-interacting protein). Coilin p80 and Sm core protein immunoreactivity, however, were seen only in the nucleus. SMN is known to associate with ?-actin mRNA and specific hnRNPs in axons and in neurite extensions of cultured nerve cells, and SMN also stimulates neurite outgrowth in cultures. Our results are therefore consistent with SMN complexes, rather than SMN alone, being involved in the transport of actin mRNPs along the axon as in the transport of snRNPs into the nucleus by similar SMN complexes. Antisense knockdown of profilin I and II isoforms inhibited neurite outgrowth of PC12 cells and caused accumulation of SMN and its associated proteins in cytoplasmic aggregates. BIAcore studies demonstrated a high affinity interaction of SMN with profilin IIa, the isoform present in developing neurons. Pathogenic missense mutations in SMN, or deletionic missense mutations in SMN, or deletion of exons 5 and 7, prevented this interaction. The interaction is functional in that SMN can modulate actin polymerisation in vitro by reducing the inhibitory effect of profilin IIa. This suggests that reduced SMN in SMA might cause axonal pathfinding defects by disturbing the normal regulation of microfilament growth by profilins

  15. Role of oxidants in mast cell activation.

    Science.gov (United States)

    Suzuki, Yoshihiro; Yoshimaru, Tetsuro; Inoue, Toshio; Niide, Osamu; Ra, Chisei

    2005-01-01

    Reactive oxygen species (ROS), such as superoxide, hydrogen peroxide (H2O2), and hydroxyl radical, have for a long time been considered as accidental by-products of respiratory energy production in mitochondria and as being useless and rather deleterious to biological systems. Contrary to such a classical view, accumulating evidence indicates that upon stimulation of divergent receptor systems, ROS are intentionally produced and even required for appropriate signal transduction and biological responses. Work by our group and that of others have shown that stimulation of mast cells through the high-affinity IgE receptor (FcepsilonRI) induces the production of ROS such as superoxide and H2O2 possibly by the phagocyte NADPH oxidase homologue and that these endogenously produced oxidants have important functions in regulation of various mast cell responses, including degranulation, leukotriene secretion, and cytokine production. Subsequent studies have defined particular biochemical pathways that can be targeted by ROS and/or cellular redox balance. More recent research reveals that ROS may also play an important role in mast cell activation by divergent allergy-relevant environmental substances, for instance heavy metals and polycyclic aromatic hydrocarbons. This review summarizes current knowledge on the role of endogenous oxidants in mast cell activation. PMID:16107761

  16. Isolated optic nerve pseudotumour

    International Nuclear Information System (INIS)

    Isolated optic nerve involvement by the idiopathic inflammatory process is a rare finding and very few reports are available. Here a case of an isolated optic nerve inflammatory pseudotumour presenting with gradually progressive unilateral loss of vision is described. It showed dramatic response to a trial of steroids and its differential diagnoses are discussed. Copyright (1999) Blackwell Science Pty Ltd

  17. Techniques of facial nerve block.

    Science.gov (United States)

    Schimek, F; Fahle, M

    1995-01-01

    The efficacy of different techniques of facial nerve block for cataract surgery was investigated. Forty four patients underwent either modified O'Brien, Atkinson, van Lint, or lid blocks. Intentional muscle activity of the orbicularis oculi muscle was recorded and the area under the EMG curve calculated for quantitative comparison of muscle activity between the groups before and after injection of lignocaine with the vasoconstrictor naphazoline nitrate. In addition, the force of lid closure was measured and lid motility determined on a subjective score scale. Whereas the modified O'Brien and lid blocks nearly abolished the muscle activity recorded in the EMG (p < 0.003), the Atkinson and van Lint blocks did not significantly affect these variables. The O'Brien and lid blocks decreased the force of lid closure and lid movements far more effectively than the Atkinson and van Lint blocks (p < 0.0001). The topographic distribution of a mixture of metrizamide and lignocaine solutions was evaluated radiographically in eight additional patients, to assess potential causes for differences in the efficacy of the block techniques. The radiological results showed involvement of the region of the facial nerve trunk and its temporal and cervical divisions by the modified O'Brien block. The lid block, on the other hand, affected terminal branches of the facial nerve's temporal division. In this study, complete lid akinesia was achieved by both the modified O'Brien block and the lid block. However, because the modified O'Brien block involves the risk of neural injury to the facial nerve or its main divisions, the lid block is recommended as the most effective and safe method to achieve akinesia of the orbicularis oculi muscle. Images PMID:7696239

  18. Comparative Diagnostic Accuracy of Ganglion Cell-Inner Plexiform and Retinal Nerve Fiber Layer Thickness Measures by Cirrus and Spectralis Optical Coherence Tomography in Relapsing-Remitting Multiple Sclerosis

    OpenAIRE

    Julio J. González-López; Gema Rebolleda; Marina Leal; Noelia Oblanca; Francisco J. Muñoz-Negrete; Lucienne Costa-Frossard; José C. Álvarez-Cermeño

    2014-01-01

    Objective. To estimate sensitivity and specificity of several optical coherence tomography (OCT) measurements for detecting retinal thickness changes in patients with relapsing-remitting multiple sclerosis (RRMS), such as macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with Cirrus (OCT) and peripapillary retinal nerve fiber layer (pRNFL) thickness measured with Cirrus and Spectralis OCT. Methods. Seventy patients (140 eyes) with RRMS and seventy matched healthy subjects...

  19. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach

    2005-01-01

    The oxygen tension of the optic nerve is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The oxygen tension is autoregulated and moderate changes in intraocular pressure or blood pressure do not affect the optic nerve oxygen tension. If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. A disturbance in oxidative metabolism in the cytochromes of the optic nerve can be seen at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen tension. Lowering the intraocular pressure tends to increase the optic nerve oxygen tension, even though this effect may be masked by the autoregulation when the optic nerve oxygen tension and perfusion pressure is in the normal range. Carbonic anhydrase inhibitors increase the optic nerve oxygen tension through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by the cyclo-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical trials and needed to test this hypotheses.

  20. Effectiveness of nocturnal home oxygen therapy to improve exercise capacity, cardiac function and cardiac sympathetic nerve activity in patients with chronic heart failure and central sleep apnea

    International Nuclear Information System (INIS)

    Central sleep apnea, often found in patients with chronic heart failure (CHF), has a high risk of poor prognosis. This study involved 20 patients with CHF (left ventricular ejection fraction (LVEF) 5 times/h who were divided into 2 groups: 10 patients treated with nocturnal home oxygen therapy (HOT) and 10 patients without HOT (non-HOT). All patients had dilated cardiomyopathy and underwent overnight polysomnography, cardiopulmonary exercise testing, and nuclear cardiac examinations to evaluate AHI, exercise capacity according to the specific activity scale and oxygen uptake at anaerobic threshold and peak exercise (peak VO2). Cardiac function according to 99mTc-methoxyisobutylisonitrile (MIBI) QGS, and the total defect score (TDS), H/M ratio and the washout rate (WR) on 123I-metaiodobenzylguanidine (MIBG) imaging were calculated for all patients. As compared with the non-HOT group, the HOT group demonstrated a greater reduction in AHI (26.1±9.1 to 5.1±3.4), 123I-MIBG TDS (31±8 to 25±9), and 123I-MIBG WR (48±8% to 41±5%) and a greater increase in the specific activity scale (4.0±0.9 to 5.8±1.2 Mets), peak VO2 (16.0±3.8 to 18.3±4.7 ml·min-1·kg-1), and LVEF (27±9% to 37±10%). HOT improves exercise capacity, cardiac function, and cardiac sympathetic nerve activity in patients with CHF and central sleep with CHF and central sleep apnea. (author)

  1. Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting

    OpenAIRE

    Hagbom, Marie; Istrate, Claudia; Engblom, David; Karlsson, Thommie; Rodriguez-Diaz, Jesus; Buesa, Javier; Taylor, John A.; Loitto, Vesa; Magnusson, Karl-Eric; Ahlman, Hakan; Lundgren, Ove; Svensson, Lennart

    2011-01-01

    otavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves...

  2. H-REFLEX UP-CONDITIONING ENCOURAGES RECOVERY OF EMG ACTIVITY AND H-REFLEXES AFTER SCIATIC NERVE TRANSECTION AND REPAIR IN RATS

    OpenAIRE

    Chen, Yi; Wang, Yu; Chen, Lu; Sun, Chenyuo; English, Arthur W.; Wolpaw, Jonathan R; Chen, Xiang Yang

    2010-01-01

    Operant conditioning of the spinal stretch reflex or its electrical analog, the H-reflex, produces spinal cord plasticity and can thereby affect motoneuron responses to primary afferent input. To explore whether this conditioning can affect the functional outcome after peripheral nerve injury, we assessed the effect of up-conditioning soleus (SOL) H-reflex on SOL and tibialis anterior (TA) function after sciatic nerve transection and repair. Sprague-Dawley rats were implanted with EMG electro...

  3. Células binucleadas no núcleo do nervo hipoglosso humano através dos grupos etários / Binucleated nerve cells in the human nucleus n. hypoglossi through ages

    Scientific Electronic Library Online (English)

    Cecil José, Rezze.

    1966-12-01

    Full Text Available Foram contadas e estudadas as células uni- e binucleadas do núcleo do nervo hipoglosso humano de 26 indivíduos brancos e do sexo masculino, com idades variando entre 4 meses a 86 anos, todos sem processos patológicos que presumivelmente determinassem alterações nas células nervosas. Os cortes seriad [...] os com 30µ de espessura, foram corados pelo método de Pal Weigert modificado por Erhart, sendo feita coloração de fundo pelo picrocarmim. Mediante comparação dos diâmetros medidos ortogonalmente foi verificado, pelo estudo estatístico, que as células binucleadas eram maiores que as uninucleadas. O pequeno número de células binucleadas (33 em 202.910 células contadas), sua distribuição indiferente nos diversos grupos etários e a ausência de figuras de reprodução mitótica ou amitótica, levam à conclusão de que a sua presença não caracteriza um processo de involução senil. O significado deste achado que tem sido atribuído a processo de divisão celular mitótica ou amitótica, à divisão nuclear ou nucleolar sem chegar à divisão citoplasmática ou à fusão de duas células uninucleadas, é discutido à luz dos dados constantes da literatura. Abstract in english It has been generally accepted that mature neurons of the central nervous system of adult mammals are incapable of cell-division. Nevertheless, recent data are suggesting the contrary. Mature neurons, bi- or multinucleated, observed in the central nervous system of vertebrates, mammals and man are b [...] eing differently interpreted: as a result of mitotic or amitotic cell-division of mature neurons; as indiferentiated cells which could indicate a regeneration process; as a cellular reaction to nervous injuries; as the result of the fusion between two mononucleated elements. The cells of the human nucleus n. hypoglossi were counted an studied in 26 white males, the youngest four months old, the eldest, eightysix years old. The material secured at the necropsy table was selected in order to exclude diseases or physical conditions which could interfere with the final results. The medulla oblongata were formalin fixed, imbedded in celloidin, 30µ serial cross sectioned, numbered and stained by Pal-Weigert modified by Erhart method for myelin sheaths. The counterstain was by carmin. The cells were counted when their cell-bodies showed evident nucleus and nucleolus. They were measured and carefully analysed including with high magnification. From the 202.910 counted cells, 33 were binucleated. These latter did not present any characteristic of mitotic or amitotic cell-division an no relation between age and higher frequency of binucleated cells could be observed. The general morphology of the binucleated cells was equivalent to the mononucleated ones although the former were significantly larger than the latter. The statistical analysis was made by comparision of sample mean of two populations at the five per cent level of significance. It is concluded, considering the studied material and the current literature, that there is no reason to accept, the presence of binucleated nerve cells as a biological reaction due to old age. The real significance of these cells is still unknown, but it can be admitted that they should have a biological capacity which would be qualitatively the same in the differente ages. Nevertheless, their quantitative evaluation is not possible, as far as we know.

  4. Deficiency of Small Gtpase Rac2 Affects T Cell Activation

    OpenAIRE

    Yu, Hong; Leitenberg, Dave; Li, Baiyong; Flavell, Richard A.

    2001-01-01

    Rac2 is a hematopoietic-specific GTPase acting as a molecular switch to mediate both transcriptional activation and cell morphological changes. We have examined the effect of Rac2 deficiency during T cell activation. In Rac2?/? T cells, proliferation was reduced upon stimulation with either plate-bound anti-CD3 or T cell receptor–specific antigen. This defect is accompanied with decreased activation of mitogen activated protein kinase extracellular signal–regulated kinase (ERK)1/2 and...

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

    Science.gov (United States)

    Zhang, Pei-xun; Li-ya, A; Kou, Yu-hui; Yin, Xiao-feng; Xue, Feng; Han, Na; Wang, Tian-bing; Jiang, Bao-guo

    2015-01-01

    The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair peripheral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good histocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration (2–8 weeks), the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objective and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury. PMID:25788923

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

    Directory of Open Access Journals (Sweden)

    Pei-xun Zhang

    2015-01-01

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

  7. A novel chondroitin sulfate hydrogel for nerve repair

    Science.gov (United States)

    Conovaloff, Aaron William

    Brachial plexus injuries affect numerous patients every year, with very debilitating results. The majority of these cases are very severe, and involve damage to the nerve roots. To date, repair strategies for these injuries address only gross tissue damage, but do not supply cells with adequate regeneration signals. As a result, functional recovery is often severely lacking. Therefore, a chondroitin sulfate hydrogel that delivers neurotrophic signals to damaged neurons is proposed as a scaffold to support nerve root regeneration. Capillary electrophoresis studies revealed that chondroitin sulfate can physically bind with a variety of neurotrophic factors, and cultures of chick dorsal root ganglia demonstrated robust neurite outgrowth in chondroitin sulfate hydrogels. Outgrowth in chondroitin sulfate gels was greater than that observed in control gels of hyaluronic acid. Furthermore, the chondroitin sulfate hydrogel's binding activity with nerve growth factor could be enhanced by incorporation of a synthetic bioactive peptide, as revealed by fluorescence recovery after photobleaching. This enhanced binding was observed only in chondroitin sulfate gels, and not in hyaluronic acid control gels. This enhanced binding activity resulted in enhanced dorsal root ganglion neurite outgrowth in chondroitin sulfate gels. Finally, the growth of regenerating dorsal root ganglia in these gels was imaged using label-free coherent anti-Stokes scattering microscopy. This technique generated detailed, high-quality images of live dorsal root ganglion neurites, which were comparable to fixed, F-actin-stained samples. Taken together, these results demonstrate the viability of this chondroitin sulfate hydrogel to serve as an effective implantable scaffold to aid in nerve root regeneration.

  8. Arsenic toxicity in the human nerve cell line SK-N-SH in the presence of chromium and copper

    Science.gov (United States)

    HU, LIGANG; GREER, JUSTIN B.; SOLO-GABRIELE, HELENA; FIEBER, LYNNE A.; CAI, YONG

    2013-01-01

    As, Cr, and Cu represent one potential combination of multiple metals/metalloids exposures since these three elements are simultaneously leached from chromated copper arsenate (CCA)-treated wood, a common product used for building construction, at levels that can be potentially harmful. This study investigated the neurotoxicity of As associated with CCA-treated wood when accompanied by Cr and Cu. The toxicity was evaluated on basis of a cytotoxicity model using human neuroblastoma cell line SK-N-SH. The cells were cultured with CCA-treated wood leachates or with solutions containing arsenate [As(V)], divalent copper [Cu(II)], trivalent chromium [Cr(III)] alone or in different combinations of the three elements. The toxicity was evaluated using variations in cell replication compared to controls after 96 hrs exposure. Among the three elements present in wood leachates, As played the primary role in the observed toxic effects, which exerted through multiple pathways, including the generation of oxidative stress. DOM affected the absorption of metals/metalloids into the test cells, which however did not obviously appear to impact toxicity. As toxicity was enhanced by Cu(II) and inhibited by Cr(III) at concentrations below U.S. EPA’s allowable maximum contaminant levels in drinking waters. Thus assessing As toxicity in real environments is not sufficient if based solely on the result from As. PMID:23473430

  9. Long-term down-regulation of EGF-dependent tyrosine kinase activity in PC12 cells

    International Nuclear Information System (INIS)

    PC12 rat pheochromocytoma cells display cell surface receptors for both nerve growth factor (NGF) and epidermal growth factor (EGF), thus providing a model system with which to study their roles in the regulation of proliferation and differentiation. They have shown that treatment of the cells with NGF induces a progressive decrease (60-90%) in EGF receptors as monitored by [125I]EGF binding and crosslinking. In the present report they determine EGF receptor levels in membranes from control and NGF-differentiated PC12 cells by monitoring EGF-receptor kinase activity. Measuring either the phosphorylation of a src-related synthetic peptide or the autophosphorylation of the receptor itself they found specific and maximal stimulation by 10 ng/ml EGF, but not by insulin, NGF, or cytochrome C, a complete dependency on Mn2+ ions, and higher specific activity in the presence of sodium vanadate. Alkaline treatment of the autophosphorylated receptor indicates that 75% of the 32P is associated with tyrosine residues. Membranes from NGF-differentiated cells show a decrease of 60-80% and 85-95% in the tyrosine kinase activity for exogenous substrate or receptor autophosphorylation, respectively. The possibility that the low levels of EGF-dependent tyrosine kinase activity in differentiated PC12 cells is an expression of a decrease in EGF receptor numbers and/or modulation of their catalytic activity by other kinases is under investigation

  10. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    Science.gov (United States)

    Hagbom, Marie; Istrate, Claudia; Engblom, David; Karlsson, Thommie; Rodriguez-Diaz, Jesus; Buesa, Javier; Taylor, John A; Loitto, Vesa-Matti; Magnusson, Karl-Eric; Ahlman, Håkan; Lundgren, Ove; Svensson, Lennart

    2011-07-01

    Rotavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²? concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP?), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT? receptor antagonists. PMID:21779163

  11. The transcription factor Sox11 promotes nerve regeneration through activation of the regeneration-associated gene Sprr1a

    OpenAIRE

    Jing, Xiaotang; Wang, Ting; Huang, Shaohua; Joseph C. Glorioso; Albers, Kathryn M

    2011-01-01

    Factors that enhance the intrinsic growth potential of adult neurons are key players in the successful repair and regeneration of neurons following injury. Injury-induced activation of transcription factors has a central role in this process because they regulate expression of regeneration-associated genes. Sox11 is a developmentally expressed transcription factor that is significantly induced in adult neurons in response to injury. Its function in injured neurons is however undefined. Here, ...

  12. Toward a broader view of ube3a in a mouse model of angelman syndrome: expression in brain, spinal cord, sciatic nerve and glial cells.

    Science.gov (United States)

    Grier, Mark D; Carson, Robert P; Lagrange, Andre Hollis

    2015-01-01

    Angelman Syndrome (AS) is a devastating neurodevelopmental disorder characterized by developmental delay, speech impairment, movement disorder, sleep disorders and refractory epilepsy. AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene. Ube3a is expressed nearly exclusively from the maternal chromosome in mature neurons. While imprinting in neurons of the brain has been well described, the imprinting and expression of Ube3a in other neural tissues remains relatively unexplored. Moreover, given the overwhelming deficits in brain function in AS patients, the possibility of disrupted Ube3a expression in the infratentorial nervous system and its consequent disability have been largely ignored. We evaluated the imprinting status of Ube3a in the spinal cord and sciatic nerve and show that it is also imprinted in these neural tissues. Furthermore, a growing body of clinical and radiological evidence has suggested that myelin dysfunction may contribute to morbidity in many neurodevelopmental syndromes. However, findings regarding Ube3a expression in non-neuronal cells of the brain have varied. Utilizing enriched primary cultures of oligodendrocytes and astrocytes, we show that Ube3a is expressed, but not imprinted in these cell types. Unlike many other neurodevelopmental disorders, AS symptoms do not become apparent until roughly 6 to 12 months of age. To determine the temporal expression pattern and silencing, we analyzed Ube3a expression in AS mice at several time points. We confirm relaxed imprinting of Ube3a in neurons of the postnatal developing cortex, but not in structures in which neurogenesis and migration are more complete. This furthers the hypothesis that the apparently normal window of development in AS patients is supported by an incompletely silenced paternal allele in developing neurons, resulting in a relative preservation of Ube3a expression during this crucial epoch of early development. PMID:25894543

  13. Bimodal Activity of FK 506 (Tacrolimus: Low Dose FK 506-Application (0,1 mg/KG with High Neurotrophic Effectiveness on Allogenous Nerve Transplants in Rats

    Directory of Open Access Journals (Sweden)

    A. Bremerich

    2007-12-01

    Full Text Available Aim/Background: The development of nerve reconstruction procedures as an alternative to the present standard procedure of an autologous nerve transplantation is nowadays the focus of interest in clinical research of nerval regeneration. Despite of the neuro-regenerative effect of the immunosuppressive drug FK 506, the high doses used successfully up to now cannot justify the clinical application for nerval regeneration with regard to the side effects. Hence, the aim of this animal experimental study was to compare the neurotrophic effectiveness of a low dose FK 506 treatment on allogenous nerve transplants (allograft with outcomes of autologous nerve transplants (isograft to be able to estimate the valency concerning nerval regeneration. Material/Methods: The left sciatic nerve of rats of two strains (LEW and DA was harvested at a distance of 1,5 cm. Nerve reconstruction consisted of nerve transplants between rats of the same strain (Isograft n=8 and between both strains (Allograft n=8 with FK 506- application (0,1 mg/KG. 8 rats underwent no operation and were served as an untreated control group. For the appraisal of a functional nerval regeneration analyses, the Sciatic Functional Index (SFI and the Ankle Stance Angle (ASA were carried out after 4, 8, 12 and 16 weeks post operationem. The histomorphometric evaluation consisted of the density of Myeln Basic Proteine (MBP in immunohistochemically stained transversal semi- thin sections of the nerves of the experimental sides and of the non-operated sides after 16 weeks. Data of untreated animals served as references. Results: In all experimental groups nerval regeneration occurred. Superior histomorphometric and functional outcomes were seen in the group Allograft plus FK 506 (0.1 mg / kg. In this group the histomorphometric parameter and both functional parameters showed a significantly better nerve regeneration than in the Isograft group. Only in the group Allograft plus FK 506 (0.1 mg / kg no significant differences to untreated animals were found histomorphometrically. Conclusion: With low dose of FK 506 a clear neuro-regenerative effect on Allograft nerve grafts appeared. Thereby it it possible to keep the side effects low with a high effectiveness of nerval regeneration with regard to a clinical application.

  14. Drusen of the optic nerve head in CT imaging

    International Nuclear Information System (INIS)

    The optic nerve head drusen are non-cell formations, which are almost always calcified. They have a characteristic feature in CT examination, what can be helpful in differentiation from calcifications of the other origin, located in the posterior globe. Authors present cases of the optic nerve head drusen with typical feature in CT examination. (author)

  15. Suprascapular nerve entrapment.

    Science.gov (United States)

    Corò, L; Azuelos, A; Alexandre, A

    2005-01-01

    It is important to be aware of neuropathy involving the suprascapular nerve. While direct trauma to the suprascapular nerve is the usual cause (direct blow to the base of the neck or posterior shoulder, shoulder dislocation or fracture), the problem may result from overuse injuries (such as repetitive tennis serving or spiking of a volley ball), excessive horizontal adduction, weight lifting, backpacking or no apparent reason. These last three years we have operated 8 cases of suprascapular nerve neurolysis at the level of suprascapular incision, and section of the transverse scapular ligament through the back supraspinal approach. PMID:15830964

  16. Therapeutic isolation and expansion of human skeletal muscle-derived stem cells for the use of muscle-nerve-blood vessel reconstitution

    Science.gov (United States)

    Tamaki, Tetsuro; Uchiyama, Yoshiyasu; Hirata, Maki; Hashimoto, Hiroyuki; Nakajima, Nobuyuki; Saito, Kosuke; Terachi, Toshiro; Mochida, Joji

    2015-01-01

    Skeletal muscle makes up 40–50% of body mass, and is thus considered to be a good adult stem cell source for autologous therapy. Although, several stem/progenitor cells have been fractionated from mouse skeletal muscle showing a high potential for therapeutic use, it is unclear whether this is the case in human. Differentiation and therapeutic potential of human skeletal muscle-derived cells (Sk-Cs) was examined. Samples (5–10 g) were obtained from the abdominal and leg muscles of 36 patients (age, 17–79 years) undergoing prostate cancer treatment or leg amputation surgery. All patients gave informed consent. Sk-Cs were isolated using conditioned collagenase solution, and were then sorted as CD34?/CD45?/CD29+ (Sk-DN/29+) and CD34+/CD45? (Sk-34) cells, in a similar manner as for the previous mouse Sk-Cs. Both cell fractions were appropriately expanded using conditioned culture medium for about 2 weeks. Differentiation potentials were then examined during cell culture and in vivo transplantation into the severely damaged muscles of athymic nude mice and rats. Interestingly, these two cell fractions could be divided into highly myogenic (Sk-DN/29+) and multipotent stem cell (Sk-34) fractions, in contrast to mouse Sk-Cs, which showed comparable capacities in both cells. At 6 weeks after the separate transplantation of both cell fractions, the former showed an active contribution to muscle fiber regeneration, but the latter showed vigorous engraftment to the interstitium associated with differentiation into Schwann cells, perineurial/endoneurial cells, and vascular endothelial cells and pericytes, which corresponded to previous observations with mouse SK-Cs. Importantly, mixed cultures of both cells resulted the reduction of tissue reconstitution capacities in vivo, whereas co-transplantation after separate expansion showed favorable results. Therefore, human Sk-Cs are potentially applicable to therapeutic autografts and show multiple differentiation potential in vivo.

  17. Effects of Near-Infrared Laser on Neural Cell Activity

    International Nuclear Information System (INIS)

    Near-infrared laser has been used to relieve patients from various kinds of pain caused by postherpetic neuralgesia, myofascial dysfunction, surgical and traumatic wound, cancer, and rheumatoid arthritis. Clinically, He-Ne (?=632.8 nm, 780 nm) and Ga-Al-As (805 ± 25 nm) lasers are used to irradiate trigger points or nerve ganglion. However the precise mechanisms of such biological actions of the laser have not yet been resolved. Since laser therapy is often effective to suppress the pain caused by hyperactive excitation of sensory neurons, interactions with laser light and neural cells are suggested. As neural excitation requires large amount of energy liberated from adenosine triphosphate (ATP), we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat central nervous system and isolated mitochondria from brain. The diode laser was applied for 15 min with irradiance of 4.8 W/cm2 on a 2 mm-diameter spot at the brain surface. Tissue ATP content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area (opposite side of the cortex), whereas the ADP content showed no significant difference. Irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the brain tissue was increased 4.5-5.0 deg. C during the irradiation of both 830-nm and 652-nm laser light. Direct irradiation of the mitochondrial suspension did not show any wavelength-dependent acceleration ofany wavelength-dependent acceleration of respiration rate nor ATP synthesis. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from specific effect of the laser operated at 830 nm. Electrophysiological studies showed the hyperpolarization of membrane potential of isolated neurons and decrease in membrane resistance with irradiation of the laser, suggesting an activation of potassium channels. Intracellular ATP is reported to regulate some kinds of potassium channels. Possible mechanisms of laser effect on neural activity through interaction between ATP and potassium channels will be discussed

  18. Palmar Nerve Sheath Myxoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Amany Fathaddin

    2012-05-01

    Full Text Available Nerve sheath myxoma is a rare benign tumor of the peripheral nerves. It typically presents as a painless, firm, and slow growing nodule with a predilection for extremities mostly fingers and knees. Microscopically, it has characteristic multilobules of spindle cells in an abundant myxoid stroma. The cells are strongly positive for S-100 protein. However, this rare tumor is usually misdiagnosed as other more common benign neuronal tumors. This report describes a rare case of nerve sheath myxoma involving the palmar surface of a 23-year-old female. Clinically, it was diagnosed as a fibroma. It was excised and the final diagnosis was made after histopathological and comprehensive immunohistochemical examination of the specimen. The clinicopathological features of this rare tumor and its important differential diagnoses are discussed along with a brief review of the literature.

  19. Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration / Effetti della somministrazione oculare di nerve growth factor in due modelli animali di degenerazione delle cellule ganglionari retiniche

    Scientific Electronic Library Online (English)

    Valeria, Colafrancesco; Marco, Coassin; Simona, Rossi; Luigi, Aloe.

    Full Text Available The aim of this study was to investigate the effect of nerve growth factor (NGF) administration on retinal ganglion cells (RGCs) in experimentally induced glaucoma (GL) and diabetic retinopathy (DR). GL was induced in adult rats by injection of hypertonic saline into the episcleral vein of the eye a [...] nd diabetes (DT) was induced by administration of streptozoticin. Control and experimental rats were treated daily with either ocular application of NGF or vehicle solution. We found that both animal models present a progressive degeneration of RGCs and changing NGF and VEGF levels in the retina and optic nerve. We then proved that NGF eye drop administration exerts a protective effect on these models of retinal degeneration. In brief, our findings indicate that NGF can play a protective role against RGC degeneration occurring in GL and DR and suggest that ocular NGF administration might be an effective pharmacological approach.

  20. Reconstruction of sciatic nerve after traumatic injury in humans - factors influencing outcome as related to neurobiological knowledge from animal research

    Directory of Open Access Journals (Sweden)

    Maripuu Amanda

    2012-10-01

    Full Text Available Abstract Background The aim was to evaluate what can be learned from rat models when treating patients suffering from a sciatic nerve injury. Methods Two patients with traumatic sciatic nerve injury are presented with examination of motor and sensory function with a five-year follow-up. Reconstruction of the nerve injury was performed on the second and third day, respectively, after injury using sural nerve grafts taken from the injured leg. The patients were examined during follow-up by electromyography (EMG, MRI and functionalMRI (fMRI to evaluate nerve reinnervation, cell death in dorsal root ganglia (DRG and cortical activation; factors that were related to clinical history in the patients. Results One patient regained good motor function of the lower leg and foot, confirmed by EMG showing good activation in the leg muscles and some reinnervation in the foot muscles, as well as some sensory function of the sole of the foot. The other patient regained no motor (confirmed by EMG or sensory function in the leg or foot. Factors most influential on outcome in two cases were type of injury, nerve gap length and particularly type of reconstruction. A difference in follow-up and rehabilitation likely also influence outcome. MRI did not show any differences in DRG size of injured side compared to the uninjured side. fMRI showed normal activation in the primary somatosensory cortex as a response to cutaneous stimulation of the normal foot. However, none of the two patients showed any activation in the primary somatosensory cortex following cutaneous stimulation of the injured foot. Conclusions In decision making of nerve repair and reconstruction data from animal experiments can be translated to clinical practice and to predict outcome in patients, although such data should be interpreted with caution and linked to clinical experience. Rat models may be useful to identify and study factors that influence outcome after peripheral nerve repair and reconstruction; procedures that should be done correctly and with a competent team. However, some factors, such as cognitive capacity and coping, known to influence outcome following nerve repair, are difficult to study in animal models. Future research has to find and develop new paths and techniques to study changes in the central nervous system after nerve injury and develop strategies to utilize brain plasticity during the rehabilitation.

  1. Facial nerve pathology

    International Nuclear Information System (INIS)

    This paper reports MR imaging and CT used in 13 cases of facial neuromas and eight simulating lesions. On MR imaging, facial neuromas has long T1 and long T2 characteristics. In a 4-year-old girl with congenital facial palsy, CT and MR imaging demonstrated a facial neuroma involving the entire intratemporal segment of the facial nerve, including massive involvement of the greater superficial petrosal nerve extending into the vidian canal. A primary chemodectoma of the facial nerve (enhanced after administration of gadolinium) was identical to the facial neuroma on CT scans and MR images. Perineural metastatic lesions could not be differentiated from facial neuromas. Isolated granulomas of the facial nerve had CT findings similar to those of a facial neuroma

  2. Lymphoma Nerve Infiltration

    Directory of Open Access Journals (Sweden)

    Baehring JM

    2014-01-01

    Full Text Available Neurolymphomatosis (NL denotes the invasion of cranial nerves, nerve roots, plexus, or nerves by Non-Hodgkin lymphoma (NHL or leukaemia. This occurs in the absence (primary NL or presence (primary NL of systemic NHL. Clinical patterns include a painful polyneuropathy or polyradiculopathy, cranial neuropathy, painless polyneuropathy, and peripheral mononeuropathy. Integration of clinical information, imaging findings, as well as histopathologic examination of involved nerves or non-neural tissue, and cerebrospinal fluid analysis are needed to establish the diagnosis. Timely recognition of the disease and its exact neuroanatomical extent is the basis for successful therapy using systemic chemotherapy and localized irradiation of bulky disease sites. More complex regimens are required when cerebrospinal fluid and systemic disease sites are affected.

  3. Sacral nerve stimulation

    Directory of Open Access Journals (Sweden)

    Besendörfer M.

    2004-01-01

    Full Text Available The current concept of recruiting residual function of an inadequate pelvic organ by electrostimulation involves stimulation of the sacral spinal nerves at the level of the sacral canal. The rationale for applying SNS to fecal incontinence was based on clinical observations of its effect on bowel habits and anorectal continence function in urologic patients (increased anorectal angulation and anal canal closure pressure and on anatomic considerations: dissection demonstrated a dual peripheral nerve supply of the striated pelvic floor muscles that govern these functions. Because the sacral spinal nerve site is the most distal common location of this dual nerve supply, stimulating here can elicit both functions. Since the first application of SNS in fecal incontinence in 1994, this technique has been improved, the patient selection process modified, and the spectrum of indications expanded. At present SNS has been applied in more than 1300 patients with fecal incontinence limited.

  4. Femoral nerve dysfunction

    Science.gov (United States)

    ... surgical removal of tumors or other growths that press on the nerve. Pain medication, if necessary. Various ... complication is repeated and unnoticed injury to the leg. When there is muscle weakness, falls and related ...

  5. Cervical Radiculopathy (Pinched Nerve)

    Science.gov (United States)

    ... takes advantage of the anti-in? ammatory e? ects similar to oral steroids. The injection may be ... the nerve to recover with more time. Surgical Treatment There are several surgical procedures for radiculopathy. The ...

  6. Activity and Regulation of Telomerase in Malignant Cells

    OpenAIRE

    Lindkvist, Anna

    2006-01-01

    An important step in tumorgenesis is the acquisition of cellular immortality. Tumor cells accomplish this by activating the enzyme telomerase, and thereby avoiding replicative senescence. The aim of this thesis was to study the activity and regulation of telomerase in a panel of malignant cell types. We found that TGF-?1 (transforming growth factor-?1) mediated differential effects on telomerase activity in five ATC (anaplastic thyroid carcinoma) cell lines. Cells that harbored a p53 mutati...

  7. Peripheral nerve morphogenesis induced by scaffold micropatterning.

    Science.gov (United States)

    Cerri, Federica; Salvatore, Luca; Memon, Danish; Martinelli Boneschi, Filippo; Madaghiele, Marta; Brambilla, Paola; Del Carro, Ubaldo; Taveggia, Carla; Riva, Nilo; Trimarco, Amelia; Lopez, Ignazio D; Comi, Giancarlo; Pluchino, Stefano; Martino, Gianvito; Sannino, Alessandro; Quattrini, Angelo

    2014-04-01

    Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous micro-structure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold's micro-structure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration. PMID:24559639

  8. Human distal sciatic nerve fascicular anatomy: Implications for ankle control using nerve-cuff electrodes

    OpenAIRE

    Kenneth J Gustafson, Phd; Yanina Grinberg, Ms; Sheeba Joseph, Bs; Ronald J Triolo, Phd

    2012-01-01

    The design of neural prostheses to restore standing balance, prevent foot drop, or provide active propulsion during ambulation requires detailed knowledge of the distal sciatic nerve anatomy. Three complete sciatic nerves and branches were dissected from the piriformis to each muscle entry point to characterize the branching patterns and diameters. Fascicle maps were created from serial sections of each distal terminus below the knee through the anastomosis of the tibial and common fibular ne...

  9. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    International Nuclear Information System (INIS)

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. 123I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  10. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Nakata, Tomoaki [Sapporo Medical University School of Medicine, Second (Cardiology) Department of Internal Medicine, Sapporo, Hokkaido (Japan)

    2014-09-15

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. {sup 123}I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  11. No-carrier-added versus carrier-added123I-metaiodobenzylguanidine for the assessment of cardiac sympathetic nerve activity

    International Nuclear Information System (INIS)

    No-carrier-added (nca) MIBG is primarily associated with specific uptake (i.e. uptake-1 mechanism). We evaluated the hypothesis that nca MIBG will be less influenced by changes in extra-neuronal uptake (i.e. uptake-2 mechanism) compared with carrier-added (ca) MIBG. No-carrier-added MIBG was compared with ca MIBG of two different manufacturers (ca MIBG-1 and ca MIBG-2, with a specific activity of 200 Mq/?mol and 40 MBq/?mol MIBG respectively) in rats (n=6 per group): controls, blocking uptake-1 (desipramine) and blocking uptake-2 (phenoxybenzamine hydrochloride). Dedicated pinhole SPECT was performed 2 h after injection of the radiotracer. After SPECT, biodistribution was assessed [% injected dose per gram tissue (%ID)]. No-carrier-added MIBG had the highest absolute cardiac uptake. Although a clear trend was observed, nca MIBG was not statistically significantly different from ca MIBG-1 (0.31±0.05 %ID vs 0.25±0.01 %ID,p=0.05). Blocking uptake-1 resulted in a significant decrease in absolute cardiac uptake only for nca MIBG (0.22±0.03 %ID,p=0.004). Blocking uptake-2 resulted in a significant reduction in ca MIBG-1 cardiac uptake (0.14±0.02 %ID,p=0.0001), but not in the cardiac uptake of nca MIBG or MIBG-2. SPECT showed the highest relative cardiac uptake for nca MIBG. Poor contrast between myocardium and surrounding tissue hampered assessment of relative cardiac uptake on SPECT of both ca MIBG-1 and ca MIBG-2. No-carrier-added MIBG yields a higher myocardial upt MIBG yields a higher myocardial uptake than ca MIBG and is associated with a higher specific as well as a lower non-neuronal uptake. We therefore conclude that for the scintigraphic assessment of the myocardial sympathetic nervous system, nca MIBG is to be preferred over ca MIBG. (orig.)

  12. Numerical and experimental studies of mechanisms underlying the effect of pulsed broadband terahertz radiation on nerve cells

    Science.gov (United States)

    Duka, M. V.; Dvoretskaya, L. N.; Babelkin, N. S.; Khodzitskii, M. K.; Chivilikhin, S. A.; Smolyanskaya, O. A.

    2014-08-01

    We have studied the mechanisms underlying the effect of pulsed broadband terahertz radiation on the growth of neurites of sensory ganglia using a comparative analysis of measured reflection spectra of ganglion neurites (in the frequency range 0.1 – 2.0 THz) and spectra obtained by numerical simulation with CST Microwave Studio. The observed changes are shown to be mainly due to pulse energy absorption in the ganglion neurites. Of particular interest are the observed single resonance frequencies related to resonance size effects, which can be used to irradiate ganglia in order to activate their growth.

  13. Extracellular microvesicles from astrocytes contain functional glutamate transporters: regulation by protein kinase C and cell activation.

    Science.gov (United States)

    Gosselin, Romain-Daniel; Meylan, Patrick; Decosterd, Isabelle

    2013-01-01

    Glutamate transport through astrocytic excitatory amino-acid transporters (EAAT)-1 and EAAT-2 is paramount for neural homeostasis. EAAT-1 has been reported in secreted extracellular microvesicles (eMV, such as exosomes) and because the protein kinase C (PKC) family controls the sub-cellular distribution of EAATs, we have explored whether PKCs drive EAATs into eMV. Using rat primary astrocytes, confocal immunofluorescence and ultracentrifugation on sucrose gradient we here report that PKC activation by phorbol myristate acetate (PMA) reorganizes EAAT-1 distribution and reduces functional [(3)H]-aspartate reuptake. Western-blots show that EAAT-1 is present in eMV from astrocyte conditioned medium, together with NaK ATPase and glutamine synthetase all being further increased after PMA treatment. However, nanoparticle tracking analysis reveals that PKC activation did not change particle concentration. Functional analysis indicates that eMV have the capacity to reuptake [(3)H]-aspartate. In vivo, we demonstrate that spinal astrocytic reaction induced by peripheral nerve lesion (spared nerve injury, SNI) is associated with a phosphorylation of PKC ? together with a shift of EAAT distribution ipsilaterally. Ex vivo, spinal explants from SNI rats release eMV with an increased content of NaK ATPase, EAAT-1 and EAAT-2. These data indicate PKC and cell activation as important regulators of EAAT-1 incorporation in eMV, and raise the possibility that microvesicular EAAT-1 may exert extracellular functions. Beyond a putative role in neuropathic pain, this phenomenon may be important for understanding neural homeostasis and a wide range of neurological diseases associated with astrocytic reaction as well as non-neurological diseases linked to eMV release. PMID:24368897

  14. Extracellular Microvesicles from Astrocytes Contain Functional Glutamate Transporters: Regulation by Protein Kinase C and Cell Activation

    Directory of Open Access Journals (Sweden)

    Romain-DanielGosselin

    2013-12-01

    Full Text Available Glutamate transport through astrocytic excitatory amino-acid transporters (EAAT-1 and EAAT-2 is paramount for neural homeostasis. EAAT-1 has been reported in secreted extracellular microvesicles (eMV, such as exosomes and because the Protein Kinase C (PKC family controls the sub-cellular distribution of EAATs, we have explored whether PKCs drive EAATs into eMV. Using rat primary astrocytes, confocal immunofluorescence and ultracentrifugation on sucrose gradient we here report that PKC activation by phorbol myristate acetate (PMA reorganizes EAAT-1 distribution and reduces functional [3H]-aspartate reuptake. Western-blots show that EAAT-1 is present in eMV from astrocyte conditioned medium, together with NaK ATPase and glutamine synthetase all being further increased after PMA treatment. However, nanoparticle tracking analysis reveals that PKC activation did not change particle concentration. Functional analysis indicates that eMV have the capacity to reuptake [3H]-aspartate. In vivo, we demonstrate that spinal astrocytic reaction induced by peripheral nerve lesion (spared nerve injury, SNI is associated with a phosphorylation of PKC ? together with a shift of EAAT distribution ipsilaterally. Ex vivo, spinal explants from SNI rats release eMV with an increased content of NaK ATPase, EAAT-1 and EAAT-2. These data indicate PKC and cell activation as important regulators of EAAT-1 incorporation in eMV, and raise the possibility that microvesicular EAAT-1 may exert extracellular functions. Beyond a putative role in neuropathic pain, this phenomenon may be important for understanding neural homeostasis and a wide range of neurological diseases associated with astrocytic reaction as well as non-neurological diseases linked to eMV release.

  15. Transient suppression of AHR activity in early red seabream embryos does not prevent the disruption of peripheral nerve projection by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    Science.gov (United States)

    Iida, Midori; Bak, Su-Min; Murakami, Yasunori; Kim, Eun-Young; Iwata, Hisato

    2014-09-01

    The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is mainly mediated by an aryl hydrocarbon receptor (AHR), which regulates the transcription of multiple target genes including cytochrome P450 1A (CYP1A). Our pervious study identified the presence of TCDD-induced defects of peripheral nerve projection in red seabream (Pagrus major) embryos. However, it remains unclear whether the TCDD-induced peripheral neurotoxicity is mediated by the AHR. To assess the contribution of the red seabream AHR (rsAHR) signaling pathway to the neuronal toxicity, red seabream embryos at 10h post-fertilization (hpf) were treated for 80 min with TCDD (0, 0.3, 5.3, and 37 nM in seawater) alone or in combination with CH223191 (500 nM in seawater), which is an AHR antagonist. A preliminary in vitro reporter gene assay confirmed that TCDD-induced transcriptional activity via rsAHR1 and rsAHR2 was suppressed by CH223191 treatment in a dose-dependent manner. CYP1A mRNA expression in embryos was determined by 2-step real time quantitative-polymerase chain reaction at 24 and 120 hpf and in situ hybridization at 48, 72, 96 and 120 hpf. The morphology of the peripheral nerve system (PNS) was also microscopically observed by fluorescent staining using an anti-acetylated tubulin antibody at 120 hpf. CYP1A mRNA expression was dose-dependently induced by TCDD at all of the examined developing stages. The suppression of TCDD-induced CYP1A expression by CH223191 treatment was observed in embryos at 24 and 48 hpf, while the effect of the rsAHR antagonist disappeared at 96 and 120 hpf. This phenomenon indicated the transient suppression of TCDD-induced rsAHR activation by CH223191 treatment. The immunostaining of peripheral nerves at 120 hpf demonstrated that the projections of the craniofacial nerve were altered in TCDD-treated embryos, and the frequency of TCDD-induced abnormal projections was not prevented by co-treatment with CH223191. These results indicate that the transient suppression of TCDD-induced rsAHR activation during the early developing stages of the red seabream does not influence the abnormal projection of peripheral nerves. In conclusion, transient rsAHR activation in the early stages of development is not involved in the neurotoxicity. PMID:24858342

  16. Immune Responses Following Mouse Peripheral Nerve Xenotransplantation in Rats

    Directory of Open Access Journals (Sweden)

    Lai-Jin Lu

    2009-01-01

    Full Text Available Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation, but the strong xenoimmune responses pose a major obstacle to its application in the clinic. In this study, we investigate the rejection of mouse peripheral nerve xenografts in rats. Severe intragraft mononuclear cell infiltration, graft distension, and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation. The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However, mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines, including IL-2, IFN-?, and TNF-?. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection.

  17. Study on telomerase activity during radiation-induced cells death

    International Nuclear Information System (INIS)

    Objective: To investigate changes of telomerase activity in human tumor and normal cell lines exposed to radiation and its association with cell death. Methods Telomerase activity was assayed, telomerase in situ hybridization was performed,dead cells were numbered, and morphology of the dead cells was distinguished at different time, point after irradiation. Results: Apoptosis was the primary cause of cell death of A549 and L02 cell lines. In the development of apoptosis, positive cells by telomerase in situ hybridization accounted for 60% to 90% of the two lines, and the expression intensity of telomerase activity assayed by TRAP increased, suggesting that radiation injury could induce telomerase activity and that the high level of telomerase activity might be maintained till the development of apoptosis. Conclusion: Telomerase suppression may not be involved in radiation-induced human tumor and normal cell apoptosis and telomerase participates in the process of chromosomal repair

  18. Involvement of Nuclear Factor of Activated T Cells Activation in UV Response: EVIDENCE FROM CELL CULTURE AND TRANSGENIC MICE*

    OpenAIRE

    Huang, Chuanshu; Mattjus, Peter; Ma, Wei-Ya; Rincon, Mercedes; Chen, Nan-yue; Brown, Rhoderick E; DONG, ZIGANG

    2000-01-01

    Mammalian cells respond to UV radiation by signaling cascades leading to activation of transcription factors, such as activated protein 1, NF?B, and p53, a process known as the “UV response.” Nuclear factor of activated T cells (NFAT) was first identified as an inducible nuclear factor in immune response and subsequently found to be expressed in other tissues and cells. To date, however, the regulation and function of NFAT in tissues and cells, other than the immune system, are not well ...

  19. Combined treatment with FK506 and nerve growth factor for spinal cord injury in rats

    OpenAIRE

    Chen, Guang; Zhang, Zhen; Wang, Shouyu; Lv, Decheng

    2013-01-01

    Following spinal cord injury in rats, FK506 is able to protect local nerve tissue, promote neural regeneration, reduce neuronal apoptosis and accelerate the recovery of spinal cord functions. Nerve growth factor (NGF) is important in the regulation of central and peripheral nerve cell regeneration, growth differentiation and functions. Previous studies have shown that FK506 and NGF exhibit a synergistic effect in the treatment of peripheral nerve injury; however, it remains unclear whether th...

  20. The Unfolded Protein Response is a Major Mechanism by which LRP1 Regulates Schwann Cell Survival After Injury

    OpenAIRE

    Mantuano, Elisabetta; Henry, Kenneth; Yamauchi, Tomonori; Hiramatsu, Nobuhiko; Yamauchi, Kazuyo; Orita, Sumihisa; TAKAHASHI, KAZUHISA; Lin, Jonathan H.; Gonias, Steven L.; Campana, W. Marie

    2011-01-01

    In peripheral nerve injury, Schwann cells (SCs) must survive to exert a continuing and essential role in successful nerve regeneration. Herein, we show that peripheral nerve injury is associated with activation of endoplasmic reticulum (ER) stress and the adaptive unfolded protein response (UPR). The UPR culminates in expression of C/EBP homology protein CHOP, a pro-apoptotic transcription factor in SCs, unless counteracted by LDL receptor-related protein-1 (LRP1), which serves as a major act...

  1. Acidic and basic fibroblast growth factors in the nervous system: distribution and differential alteration of levels after injury of central versus peripheral nerve.

    Science.gov (United States)

    Eckenstein, F P; Shipley, G D; Nishi, R

    1991-02-01

    Acidic and basic fibroblast growth factors (aFGF and bFGF) are known to stimulate mitogenesis in a variety of non-neuronal cell types. Recent work has also established that FGFs can act as neurotrophic factors that promote the survival and regeneration in vitro of a variety of neurons. The present study investigates the distribution of aFGF and bFGF in vivo by using a mitogenic bioassay on AKR-2B cells coupled with Western-blot analysis to estimate the levels of aFGF and bFGF in different areas of the rat nervous system. Acidic FGF and bFGF from extracts of nervous tissue were found to differ considerably in their relative dependencies upon heparin to potentiate their mitogenic activities: the effect of aFGF was strongly dependent upon heparin, whereas the effect of bFGF was only slightly potentiated by heparin. Heparin was also found to stimulate differentially the mitogenic activity of extracts prepared from different areas of the nervous system, indicating that spinal cord, cortex, pituitary, and optic nerve contained different ratios of aFGF to bFGF, whereas sciatic nerve contained extremely high levels of only aFGF. These results were confirmed in Western-blot experiments, using antibodies specific for either aFGF or bFGF. Transection of nerves had opposing effects in sciatic and optic nerves: aFGF rapidly declined in the sciatic nerve distal to the cut, whereas bFGF increased slightly in the distal portion of the cut optic nerve. This differential effect of injury on FGF levels in central versus peripheral nerves may reflect the differential regenerative potential of these two types of nerves. PMID:1992009

  2. Active Inhibition of Plasma Cell Development in Resting B Cells by Microphthalmia-associated Transcription Factor

    OpenAIRE

    Lin, Ling; Gerth, Andrea J.; P