WorldWideScience
1

Intraneural activated T cells cause focal breakdown of the blood-nerve barrier.  

Science.gov (United States)

Experiments were conducted to investigate the effect of activated T cells on the blood-nerve barrier (BNB) in experimental allergic neuritis (EAN). T cells reactive to the P2 component of myelin (P2 T cells) and known to cause EAN were injected into the sciatic nerve of Lewis rats. Animals were then given daily intraperitoneal (i.p.) injections of serum with known demyelinating activity (rabbit EAN serum) or control serum. Serial nerve conduction studies across the injected segment were performed and nerves were removed at various stages for histology. Focal conduction block and perivascular demyelination were evidence in T cell injected nerves of animals treated with EAN serum. In animals treated with control serum no conduction block was seen and only perivascular infiltrates without demyelination were present. Similar results were obtained with T cells reactive to non-neural antigens, although the effect was less marked. Systemically administered rabbit immunoglobulin (Ig) was demonstrated within the endoneurium of P2 T cell injected nerves by immunofluorescence and the endoneurial blood vessels showed increased permeability to circulating horseradish peroxidase (HRP). These findings demonstrate that activated T cells cause focal breakdown of the BNB, allowing circulating antimyelin antibody to enter the endoneurium with consequent focal demyelination. P2 reactive EAN producing T cells do not cause significant demyelination when injected intraneurally (i.n.) in the absence of circulating antimyelin antibody. Intraneural injection of tumour necrosis factor alpha (TNF-alpha) yielded similar results, causing conduction block and perivascular demyelination in the presence of circulating antimyelin antibody but not in control serum treated animals. PMID:7655884

Spies, J M; Westland, K W; Bonner, J G; Pollard, J D

1995-08-01

2

Assessment of nerve morphology in nerve activation during electrical stimulation  

Science.gov (United States)

The distance between nerve and stimulation electrode is fundamental for nerve activation in Transcutaneous Electrical Stimulation (TES). However, it is not clear the need to have an approximate representation of the morphology of peripheral nerves in simulation models and its influence in the nerve activation. In this work, depth and curvature of a nerve are investigated around the middle thigh. As preliminary result, the curvature of the nerve helps to reduce the simulation amplitude necessary for nerve activation from far field stimulation.

Gomez-Tames, Jose; Yu, Wenwei

2013-10-01

3

Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells.  

Science.gov (United States)

Neurotrophic factors are essential to maintain and organize neurons functionally; thereby neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases such as Alzheimer's disease. In the present study, we firstly examined the effects of ethanol extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and Agaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in vivo. ddY mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the JNK pathway; these compounds are not hericenones. PMID:18758067

Mori, Koichiro; Obara, Yutaro; Hirota, Mitsuru; Azumi, Yoshihito; Kinugasa, Satomi; Inatomi, Satoshi; Nakahata, Norimichi

2008-09-01

4

Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain.  

Science.gov (United States)

Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (P<0.05). In contrast, the application of TENS at 1 week (TENS-1w) or 2 weeks (TENS-2w) after injury was ineffective in reducing hyperalgesia (mechanical and thermal) or activation of microglia and astrocytes. Early TENS decreased p-p38 within microglia (P<0.05), the expression levels of protein kinase C (PKC-?), and phosphorylated anti-phospho-cyclic AMP response element-binding protein (p-CREB) in the superficial spinal dorsal horn neurons (P<0.05), mitogen-activated protein (MAP) kinases, and proinflammatory cytokines, and increased the expression levels of opioid receptors (P<0.05). The results suggested that the application of early TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-?, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible. PMID:25010326

Matsuo, Hideaki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Watanabe, Shuji; Takeura, Naoto; Sugita, Daisuke; Shimada, Seiichiro; Nakatsuka, Terumasa; Baba, Hisatoshi

2014-09-01

5

Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus  

OpenAIRE

The anatomical and biophysical specializations of octopus cells allow them to detect the coincident firing of groups of auditory nerve fibers and to convey the precise timing of that coincidence to their targets. Octopus cells occupy a sharply defined region of the most caudal and dorsal part of the mammalian ventral cochlear nucleus. The dendrites of octopus cells cross the bundle of auditory nerve fibers just proximal to where the fibers leave the ventral and enter t...

Oertel, Donata; Bal, Ramazan; Gardner, Stephanie M.; Smith, Philip H.; Joris, Philip X.

2000-01-01

6

Pharmacology of airway afferent nerve activity  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology.

Carr Michael J

2001-05-01

7

Resistance of nerve cells to oxidative injury  

Directory of Open Access Journals (Sweden)

Full Text Available Introduction. Reactive oxygen species are particularly active in the brain and neuronal tissue, and they are involved in numerous cellular functions, including cell death and survival. Brain and oxidative stress. A high metabolic rate and an abundant supply of the transition metals make the brain an ideal target for a free radical attack. In addition, the brain has a high susceptibility to oxidative stress due to the high lipid content and relatively lower regenerative capacity in comparison with other tissues. Vulnerability of nerve cells to oxidative stress. The neurons are more vulnerable to oxidative stress than other brain cell types. In addition to the two conventional enzymes, catalase and glutathione peroxidase, peroxiredoxins remove intracellular hydrogen peroxide by reducing it to water. The recent work increasingly supports the hypothesis that peroxiredoxins are not only antioxidant proteins, but they also play a role in cell signaling by controlling hydrogen peroxide and alkyl hydroperoxide levels. The accumulating evidence demonstrates that microglia can become deleterious and damage neurons. The overactivated microglia release reactive oxygen species that cause neuronal damage in neurodegenerative diseases. Conclusion. The defense of nerve cells against reactive oxygen species - mediated oxidative damage is essential for maintaining the functionality of nerve cells. The ongoing studies show that neuron-glial compartmentalization of antioxidants is critical for the neuronal signaling by hydrogen peroxide as well as the neuronal protection.

Jovanovi? Zorica

2011-01-01

8

Olfactory ensheathing cells seeded muscle-stuffed vein as nerve conduit for peripheral nerve repair: a nerve conduction study.  

Science.gov (United States)

We evaluated bridging of 15 mm nerve gap in rat sciatic nerve injury model with muscle-stuffed vein seeded with olfactory ensheathing cells as a substitute for nerve autograft. Neurophysiological recovery, as assessed by electrophysiological analysis was faster in the constructed biological nerve conduit compared to that of autograft. PMID:24598302

Lokanathan, Yogeswaran; Ng, Min-Hwei; Hasan, Shariful; Ali, Anuar; Mahmod, Mazzre; Htwe, Ohnmar; Roohi, Sharifah Ahmad; Bt Hj Idrus, Ruszymah; Abdullah, Shalimar; Naicker, Amaramalar Selvi

2014-08-01

9

Sympathetic sprouting near sensory neurons after nerve injury occurs preferentially on spontaneously active cells and is reduced by early nerve block  

OpenAIRE

Some chronic pain conditions are maintained or enhanced by sympathetic activity. In animal models of pathological pain, abnormal sprouting of sympathetic fibers around large- and medium-size sensory neurons is observed in dorsal root ganglia (DRG). Large and medium size cells are also more likely to be spontaneously active, suggesting that sprouting may be related to neuron activity. We previously showed that sprouting could be reduced by systemic or locally applied lidocaine. In the complete...

Xie, Wenrui; Strong, Judith Ann; Li, Huiqing; Zhang, Jun-ming

2006-01-01

10

VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Vascular endothelial growth factor (VEGF and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF.

Rychkova Natalia

2006-06-01

11

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

12

Spinal Neurons Activated in Response to Pudendal or Pelvic Nerve Stimulation in Female Rats  

OpenAIRE

The overlapping distribution of spinal neurons activated with either pudendal sensory nerve or pelvic nerve stimulation was examined in the female rat using c-fos immunohistochemistry. Pudendal sensory nerve stimulation resulted in a significant increase in fos-positive cells in the ipsilateral dorsal horn and bilaterally in the medial, lateral and intermediate gray of L5-S1. Pelvic nerve stimulation resulted in significant increases of c-fos immunoreactive nuclei in the ipsilateral dorsal ho...

Wiedey, J.; Alexander, M. Sipski; Marson, L.

2008-01-01

13

Rescue of developing spinal motoneurons from programmed cell death by the GABA(A) agonist muscimol acts by blockade of neuromuscular activity and increased intramuscular nerve branching.  

Science.gov (United States)

Blockade of neuromuscular activity in the chick embryo during the period of programmed cell death of motoneurons results in a complete rescue of these cells. Understanding the cellular mechanisms that mediate this counterintuitive effect is of considerable interest with respect to the regulation of motoneuron survival during development as well as for understanding why motoneurons die pathologically. Although considerable evidence supports the role of a peripheral site of action at the neuromuscular junction in mediating the rescue of motoneurons following activity blockade, some evidence also supports a role for central nervous system (CNS) neurons. For example, the rescue of motoneurons by curare has been reported to be blocked by the GABA(A) agonist muscimol via its actions on CNS neurons. We have carried out a series of studies to further investigate this interesting observation. Surprisingly, we find that: (1) muscimol blocks activity and rescues MNs in a dose-dependent manner, similar to curare; (2) muscimol's effects on MN survival appear to be mediated by its action on intramuscular nerve branching, similar to curare; and (3) although muscimol acts centrally, the effects of muscimol on MN survival and axon branching are mediated peripherally at the neuromuscular junction, similar to curare. Because muscimol reduces MN depolarization these data also suggest that the depolarization of MNs by afferents is not required for promoting MN survival. Taken together, these data provide further evidence in support of a peripheral site of action of activity blockade in rescuing motoneurons from developmental cell death. PMID:12691735

Oppenheim, Ronald W; Calderó, Jordi; Cuitat, Dolors; Esquerda, Josep; Ayala, Victória; Prevette, David; Wang, Siwei

2003-03-01

14

Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents  

Energy Technology Data Exchange (ETDEWEB)

Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

Chen, Aiqiong; Du, Dan; Lin, Yuehe

2012-02-09

15

Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation  

Science.gov (United States)

Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

2004-01-01

16

trans activation of nerve growth factor in transgenic mice containing the human T-cell lymphotropic virus type I tax gene.  

OpenAIRE

Three lines of transgenic mice containing the human T-cell lymphotropic virus type I (HTLV-I) tax gene develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1327, 1987). Tumors and tumor cell lines derived from these mice produce neurite outgrowth from PC-12 cells and nerve growth factor (NGF), as determined...

Green, J. E.

1991-01-01

17

GTK, a Src-related tyrosine kinase, induces nerve growth factor-independent neurite outgrowth in PC12 cells through activation of the Rap1 pathway. Relationship to Shb tyrosine phosphorylation and elevated levels of focal adhesion kinase.  

Science.gov (United States)

The rat pheochromocytoma cell line PC12 is extensively used as a model for studies of neuronal cell differentiation. These cells develop a sympathetic neuron-like phenotype when cultured in the presence of nerve growth factor. The present study was performed in order to assess the role of mouse GTK (previously named BSK/IYK), a cytoplasmic tyrosine kinase belonging to the Src family, for neurite outgrowth in PC12 cells. We report that PC12 cells stably overexpressing GTK exhibit a larger fraction of cells with neurites as compared with control cells, and this response is not accompanied by an increased ERK activity. Treatment of the cells with the MEK inhibitor PD98059 did not reduce the GTK-dependent increased in neurite outgrowth. GTK expression induces a nerve growth factor-independent Rap1 activation, probably through altered CrkII signaling. We observe increased CrkII complex formation with p130(Cas), focal adhesion kinase (FAK), and Shb in PC12-GTK cells. The expression of GTK also correlates with a markedly increased content of FAK, phosphorylation of the adaptor protein Shb, and an association between these two proteins. Transient transfection of GTK-overexpressing cells with RalGDS-RBD or Rap1GAP, inhibitors of the Rap1 pathway, reduces the GTK-dependent neurite outgrowth. These data suggest that GTK participates in a signaling pathway, perhaps involving Shb, FAK and Rap1, that induces neurite outgrowth in PC12 cells. PMID:10878015

Annerén, C; Reedquist, K A; Bos, J L; Welsh, M

2000-09-15

18

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration  

OpenAIRE

Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment ...

Vyas, Alka A.; Patel, Himatkumar V.; Fromholt, Susan E.; Heffer-lauc, Marija; Vyas, Kavita A.; Dang, Jiyoung; Schachner, Melitta; Schnaar, Ronald L.

2002-01-01

19

Insight into astrocyte activation after optic nerve injury.  

Science.gov (United States)

In response to optic nerve damage, astrocytes become reactive. This reactivity can be identified by the presence of morphological and molecular changes throughout the retina and optic nerve as well as the formation of a glial scar. The process of astrocyte activation exhibits spatial and temporal characteristics, and it is finely regulated by complex signaling mechanisms. Excessive astrocyte activation plays a crucial role in progressive optic nerve injury. This review focuses on the spatial and temporal characteristics and mechanisms of astrocyte activation and discusses the modulation of astrocyte activation. Further insight into astrocyte activation might provide targets for future therapeutic interventions. © 2014 Wiley Periodicals, Inc. PMID:25257183

Yang, Xi-Tao; Huang, Guo-Hui; Feng, Dong-Fu; Chen, Kui

2015-04-01

20

The functional activity of lymphoid cells and the activity of acetylcholinesterase in nerves fibers of thymus of the different age rats after the chronic exposure to irradiation and heart  

International Nuclear Information System (INIS)

Effect of chronic separated and combined exposure to fractionated X-radiation at a total dose of 0,5 Gy (25 seances with 0,02 Gy by a day) and heat (25 seances for a 4 hours at 37 degrees) on the functional activity of thymic cells in young and mature rats were studied. The dose rate was 0,09 Gy/min, voltage 165 kV, current strength 10 mA, without filter, distance 100 cm. The activity of acetylcholinesterase was estimated histochemically, the proliferative activity of lymphocyte - by tritium incorporation in the culture of intact and con A-stimulated thymic cell. In mature animals the combined action of the physical factors was found to inhibit the proliferative activity of lymphocytes, glucose-6-phosphate dehydrogenase activity in the thymus and acetylcholinesterase activity in nerve fibers of this organ whereas isolated action of each of the factors didn't influence the investigated parameters. In young animals radiation and heat induced a considerable decrease in the acetylcholinesterase activity without influencing the DNA synthesis and glucose-6-phosphate dehydrogenase activity

21

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

OpenAIRE

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...

Maher, Pamela

2008-01-01

22

Choline Acetyltransferase Activity in Striatum of Neonatal Rats Increased by Nerve Growth Factor  

Science.gov (United States)

Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells.

Mobley, William C.; Rutkowski, J. Lynn; Tennekoon, Gihan I.; Buchanan, Karen; Johnston, Michael V.

1985-07-01

23

Aucubin promotes neurite outgrowth in neural stem cells and axonal regeneration in sciatic nerves.  

Science.gov (United States)

Aucubin is an iridoid glycoside with a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities. Recently, it has been shown that aucubin prevents neuronal death in the hippocampal CA1 region in rats with diabetic encephalopathy. In addition, it has protective effects on H2O2-induced apoptosis in PC12 cells. We have shown here that aucubin promotes neuronal differentiation and neurite outgrowth in neural stem cells cultured primarily from the rat embryonic hippocampus. We also investigated whether aucubin facilitates axonal elongation in the injured peripheral nervous system. Aucubin promoted lengthening and thickness of axons and re-myelination at 3 weeks after sciatic nerve injury. These results indicate that administration of aucubin improved nerve regeneration in the rat model of sciatic nerve injury, suggesting that aucubin may be a useful therapeutic compound for the human peripheral nervous system after various nerve injuries. PMID:25258571

Kim, Yong Min; Sim, U-Cheol; Shin, Yongsung; Kim Kwon, Yunhee

2014-09-01

24

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)

25

Transplantation of embryonic motor neurons into peripheral nerve combined with functional electrical stimulation restores functional muscle activity in the rat sciatic nerve transection model.  

Science.gov (United States)

Reinnervation of denervated muscle by motor neurons transplanted into the peripheral nerve may provide the potential to excite muscles artificially with functional electrical stimulation (FES). Here we investigated whether transplantation of embryonic motor neurons into peripheral nerve combined with FES restored functional muscle activity in adult Fischer 344 rats after transection of the sciatic nerve. One week after sciatic nerve transection, cell culture medium containing (cell transplantation group, n?=?6) or lacking (surgical control group, n?=?6) dissociated embryonic spinal neurons was injected into the distal stump of the tibial and peroneal nerves. Electrophysiological and tissue analyses were performed in the cell transplantation and surgical control groups 12?weeks after transplantation, as well as a in naïve control group (n?=?6) that received no surgery. In the cell transplantation group, ankle angle was measured during gait, with and without FES of the peroneal nerve. Ankle angle at mid-swing was more flexed during gait with FES (26.6?±?8.7°) than gait without FES (51.4?±?12.8°, p?=?0.011), indicating that transplantated motor neurons in conjunction with FES restored ankle flexion in gait, even though no neural connection between central nervous system and muscle was present. These results indicate that transplantation of embryonic motor neurons into peripheral nerve combined with FES can provide a novel treatment strategy for paralysed muscles. Copyright © 2013 John Wiley & Sons, Ltd. PMID:24668934

Kurimoto, Shigeru; Kato, Shuichi; Nakano, Tomonori; Yamamoto, Michiro; Takanobu, Nishizuka; Hirata, Hitoshi

2013-10-30

26

Receptor-mediated regional sympathetic nerve activation by leptin.  

OpenAIRE

Leptin is a peptide hormone produced by adipose tissue which acts centrally to decrease appetite and increase energy expenditure. Although leptin increases norepinephrine turnover in thermogenic tissues, the effects of leptin on directly measured sympathetic nerve activity to thermogenic and other tissues are not known. We examined the effects of intravenous leptin and vehicle on sympathetic nerve activity to brown adipose tissue, kidney, hindlimb, and adrenal gland in anesthetized Sprague-Da...

Haynes, W. G.; Morgan, D. A.; Walsh, S. A.; Mark, A. L.; Sivitz, W. I.

1997-01-01

27

Sympathetic nerve activity in takotsubo cardiomyopathy  

Directory of Open Access Journals (Sweden)

Full Text Available The maintenance of cardiovascular and cerebrovascular health is based on a complex relationship between the heart and the brain. While some responses to stress are vital for survival, mental stress has also been claimed to cause cardiovascular disease. The Japanese observation from the early 1990s of a reversible stress-induced cardiomyopathy, the takotsubo cardiomyopathy (TC, a peculiar type of left ventricular (LV dysfunction triggered by an acute strong emotional or physical stressor, supports this notion. The syndrome, mostly affecting postmenopausal women, presents signs and symptoms of acute coronary syndrome without evidence of obstructive coronary artery disease. Though the definite pathophysiology of TC remains to be identified, a catecholamine overstimulation of the myocardium is thought to underlie the pathogenesis and forms the basis for treatment of this medical entity.Direct recordings of multiunit efferent postganglionic muscle sympathetic nerve activity (MSNA were obtained from 12 female patients, 5 in the acute (24–48 hours and 7 in the recovery phase (1–6 months, with apical ballooning pattern and 12 healthy matched controls. MSNA was expressed as burst frequency (BF, burst incidence (BI and relative median burst amplitude (RMBA%. All patients were investigated with ongoing medication.MSNA was lower in patients with TC as compared to matched controls, but did not differ between the acute and recovery phase of TC. RMBA%, blood pressure and heart rate did not differ between the groups.MSNA is shown to be lower in patients with TC compared to healthy controls, suggesting that sympathetic neuronal outflow is rapidly reduced following the initial phase of TC. A distension of the ventricular myocardium, due to excessive catecholamine release over the heart in the acute phase may increase the firing rate of unmyelinated cardiac c-fibre afferents resulting in widespread sympathetic inhibition. Such a mechanism may underlie the lower MSNA reported in our patients.

Yrsa Bergmann Sverrisdóttir

2012-09-01

28

Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair.  

Science.gov (United States)

Collagen nerve guides are used clinically for peripheral nerve defects, but their use is generally limited to lesions up to 3 cm. In this study we combined collagen conduits with cells as an alternative strategy to support nerve regeneration over longer gaps. In vitro cell adherence to collagen conduits (NeuraGen(®) nerve guides) was assessed by scanning electron microscopy. For in vivo experiments, conduits were seeded with either Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC) or left empty (control group), conduits were used to bridge a 1cm gap in the rat sciatic nerve and after 2-weeks immunohistochemical analysis was performed to assess axonal regeneration and SC infiltration. The regenerative cells showed good adherence to the collagen walls. Primary SC showed significant improvement in distal stump sprouting. No significant differences in proximal regeneration distances were noticed among experimental groups. dMSC and dASC-loaded conduits showed a diffuse sprouting pattern, while SC-loaded showed an enhanced cone pattern and a typical sprouting along the conduits walls, suggesting an increased affinity for the collagen type I fibrillar structure. NeuraGen(®) guides showed high affinity of regenerative cells and could be used as efficient vehicle for cell delivery. However, surface modifications (e.g. with extracellular matrix molecule peptides) of NeuraGen(®) guides could be used in future tissue-engineering applications to better exploit the cell potential. PMID:24792394

di Summa, Pietro G; Kingham, Paul J; Campisi, Corrado C; Raffoul, Wassim; Kalbermatten, Daniel F

2014-06-20

29

Peripheral nerve extract effects on mesenchymal cells.  

OpenAIRE

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...

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

1996-01-01

30

Bilateral peripheral neural activity observed in vivo following unilateral nerve injury  

Science.gov (United States)

Manganese-enhanced magnetic resonance imaging (MRI) is a surrogate method to measure calcium content in nervous system since manganese physiologically follows calcium. Manganese is detectable in MRI and therefore visualizes structures and cell populations that actively regulate calcium. Since calcium is actively recruited for the transmission of action potentials, our purpose is to validate manganese-enhanced MRI for detection of changes in lumbar nerves related to nociception. A neuropathic pain model was created by chronic constrictive injury of the left sciatic nerve of Sprague-Dawley rats. Behavioral measurements, using von Frey’s tests, confirmed the presence of significant allodynia in the left hind limb of animals in the injured group. T1-weighted fast spin echo images were obtained of the lumbar cord and plexus of animals with injured left sciatic nerve and uninjured animals (control) scanned in a 7 Tesla magnet after intraperitoneal manganese chloride administration four weeks after surgery. Lumbar nerve roots and sciatic nerves in the injured group show increased normalized manganese-enhanced MRI signal, representing manganese enhancement, compared to the control group. In conclusion, animals with neuropathic pain in the left hind limb show increased manganese uptake in not only the injured sciatic nerve but also in the contralateral uninjured sciatic nerve on manganese-enhanced MRI in vivo. Although poorly understood, this finding corroborates ex vivo finding of bilateral nociceptive-related molecular changes in the nervous system of unilateral pain models. PMID:23638339

Behera, Deepak; Behera, Subrat; Jacobs, Kathleen E; Biswal, Sandip

2013-01-01

31

Motor neuron activation in peripheral nerves using infrared neural stimulation  

Science.gov (United States)

Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.

Peterson, E. J.; Tyler, D. J.

2014-02-01

32

Variable Patterned Pudendal Nerve Stimuli Improves Reflex Bladder Activation  

OpenAIRE

We evaluated variable patterns of pudendal nerve (PN) stimuli for reflex bladder excitation. Reflex activation of the bladder has been demonstrated previously with 20–33 Hz continuous stimulation of PN afferents. Neuronal circuits accessed by afferent mediated pathways may respond better to physiological patterned stimuli than continuous stimulation. Unilateral PN nerve cuffs were placed in neurologically intact male cats. PN stimulation (0.5–100 Hz) was performed under isovolumetric cond...

Bruns, Tim M.; Bhadra, Narendra; Gustafson, Kenneth J.

2008-01-01

33

Extracellular currents and potentials of the active myelinated nerve fiber.  

OpenAIRE

This paper is concerned with the accurate and rapid calculation of extracellular potentials and currents from an active myelinated nerve fiber in a volume conductor, under conditions of normal and abnormal conduction. The neuroelectric source for the problem is characterized mathematically by using a modified version of the distributed parameter model of L. Goldman and J. S. Albus (1968, Biophys. J., 8:596-607) for the myelinated nerve fiber. Solution of the partial differential equation asso...

Ganapathy, N.; Clark, J. W.

1987-01-01

34

Study of stimulators of DNA synthesis in nerve tissue cells  

International Nuclear Information System (INIS)

Changes in proliferative activity in different regions of the brain during ontogenesis are connected with changes in the composition and properties of regulators of cell proliferation. Extracts of regions of the brain in which active cell division takes place in a given stage of development (cortex of 15- to 17-day-old embryos or cerebellum of 8- to 10-day-old rats) can stimulate the incorporation of labeled precursors into the brain cell DNA of both newborn and adult rats. Salting out at increasing ammonium sulfate concentrations, gel filtration on Sephadex, and isoelectric focusing led to the isolation of three fractions of stimulators of DNA synthesis: in acid, neutral, and alkaline pH regions. A method is described for obtaining purified preparations and for determining some physicochemical properties of the acid activator, which is a low-molecular-weight peptide capable of noticeably stimulating the incorporation of labeled precursors into the DNA of nerve tissue cells when added to an in vitro system in a concentration of the order of 1 ?g/ml

35

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

Science.gov (United States)

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

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

2014-01-01

36

Basic behavior of migratory Schwann cells in peripheral nerve regeneration.  

Science.gov (United States)

In axonal regeneration after a peripheral nerve injury, Schwann cells migrate from the two nerve ends and at last form a continuous tissue cable across the gap which guides the axons toward the bands of Bungner. However, the behavior of migratory Schwann cells and their possible role are obscure. Using a film model in which the proximal stump of a transected nerve in mice was sandwiched between two thin plastic films, we analyzed neural regeneration in the early phase up to the 6th day after axotomy. Regenerating neurites emerged from the nodes of Ranvier adjacent to the axotomized nerve stump within 3 h after axotomy and extended along the parent nerve onto the film. All of the regenerating neurites on the surface of the film consisted of naked axons for at least 2 days after axotomy. Thereafter, Schwann cells from the proximal nerve migrated along a network of the regenerating axons and then closely attached to the axons, ensheathing them. Some of the Schwann cells advanced ahead of the axonal growth cones and were distributed over regions in which axonal extension was not yet present. As calculated from the time course of regenerating neurites, the velocity of axonal regeneration showed two phases: an initial slow phase (77 mu m/day) up to the 2nd post-operative day followed by a faster phase (283 mu m/day). The first observation of Schwann cells coincided with the onset of the second phase. In addition, the length of regenerating axons on the surface of the film containing many Schwann cells was significantly greater than that on the surface where Schwann cells were not yet present. It meant that migratory Schwann cells stimulated axons to elongate for a longer distance. Furthermore, Schwann cells from a distal stump showed a stronger ability to accelerate the axonal outgrowth than these from a proximal stump. PMID:8635545

Torigoe, K; Tanaka, H F; Takahashi, A; Awaya, A; Hashimoto, K

1996-02-01

37

NADPH-diaphorase in glandular cells and nerves and its relation to acetylcholinesterase-positive nerves in the male reproductive tract of man and guinea-pig.  

Science.gov (United States)

The presence of NADPH-diaphorase activity and acetylcholinesterase in the testis, epididymis, vas deferens, seminal vesicle, pelvic plexus, prostate and urethra of man and guinea-pig was investigated with the nitro blue NADPH technique and the thiocholine method, respectively. In human material NADPH-diaphorase activity was found in the Leydig cells, Sertoli cells and the epithelial linings of the rete testis, the excretory ducts, seminal vesicle, prostate and urethra. The guinea-pig material showed staining of the Leydig cells and spermatozoa and similar epithelial staining of the tract as man. Nerves beneath the epithelium and in the muscle layers of cauda epididymis, vas deferens, seminal vesicle, prostate and urethra were also stained. NADPH-diaphorase-positive nerve cells were seen in the pelvic plexus. Some cells also displayed acetylcholinesterase activity but others showed activity for only one of the enzymes or no activity for either enzyme. In the cauda epididymis, vas deferens, seminal vesicle, prostate and urethra acetylcholinesterase-positive nerve fibres formed a plexus beneath the secretory cells. It is concluded that NADPH-diaphorase, generally accepted as a nitric oxide synthase, is present in glandular cells of the male genital tract. The enzyme is also present in nerves, where it is partly co-localized with acetylcholinesterase. PMID:9694600

Sjöstrand, N O; Ehrén, I; Eldh, J; Wiklund, N P

1998-01-01

38

Clival giant cell tumor presenting with isolated trigeminal nerve involvement.  

Science.gov (United States)

Giant cell tumour (GCT) constitutes about 5 % of all skeletal tumors. They rarely occur in the skull. When involved, they preferentially involve the sphenoid or temporal bones. Skull-base GCTs generally present with multiple cranial nerves involvement, most commonly sixth followed by the third cranial nerve. We describe a case of clival GCT presenting with an isolated trigeminal nerve involvement in a 19-year-old man which was managed by surgery and adjuvant radiation. At 18 months of follow-up, the patient is clinically asymptomatic. Clival GCT should also be considered in the differential diagnosis of any isolated trigeminal nerve palsy. Adjuvant radiation has an important role to play in managing this tumour. PMID:23143505

Roy, Soumyajit; Joshi, Nikhil P; Sigamani, Elanthenral; Malik, Anita; Sharma, Meher C; Mohanti, Bidhu K; Sharma, Suresh C

2013-03-01

39

Adenoviral-Mediated Glial Cell Line–Derived Neurotrophic Factor Gene Transfer Has a Protective Effect on Sciatic Nerve Following Constriction-Induced Spinal Cord Injury  

OpenAIRE

Neuropathic pain due to peripheral nerve injury may be associated with abnormal central nerve activity. Glial cell-line-derived neurotrophic factor (GDNF) can help attenuate neuropathic pain in different animal models of nerve injury. However, whether GDNF can ameliorate neuropathic pain in the spinal cord dorsal horn (SCDH) in constriction-induced peripheral nerve injury remains unknown. We investigated the therapeutic effects of adenoviral-mediated GDNF on neuropathic pain behaviors, microg...

Chou, An-kuo; Yang, Ming-chang; Tsai, Hung-pei; Chai, Chee-yin; Tai, Ming-hong; Kwan, Aij-li; Hong, Yi-ren

2014-01-01

40

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

41

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

Energy Technology Data Exchange (ETDEWEB)

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 × 10{sup 5} 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.

Duan, Xiao-Hui, E-mail: duanxiaohui-128@163.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Cheng, Li-Na, E-mail: kobe10716@163.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Zhang, Fang, E-mail: xinxin110007@yahoo.com.cn [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Liu, Jun, E-mail: docliujun@hotmail.com [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Guo, Ruo-Mi, E-mail: guoruomi-521@163.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Zhong, Xiao-Mei, E-mail: enough300@yahoo.com.cn [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Wen, Xue-Hua, E-mail: xuehuasuqian@126.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Shen, Jun, E-mail: junshenjun@hotmail.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China)

2012-09-15

42

Internal superior laryngeal nerve afferent activity during respiration and evoked vocalization in cats.  

Science.gov (United States)

The purpose of this project was to identify and categorize patterns of activity of the internal branch of the superior laryngeal nerve during vocalization evoked by midbrain stimulation in cats anesthetized with alpha-chloralose. Unit activity was isolated from the cut distal end of the internal branch of the superior laryngeal nerve by means of floating bipolar electrodes that retained their contact with nerve fibers despite movement due to vocalization. The phases of respiration and vocalization were determined with a diaphragm electromyogram, a photoglottogram, and a microphone recording. Five groups of discrete afferent activities were defined according to relationships between the spike activity and the phases of vocalization. Group 1 cell activity peaked just before phonation, during expiratory airflow (n = 26). Group 2 cells (n = 19) followed a vocal fold vibratory pattern during phonation. Group 3 cell activity (n = 6) peaked during phonation, but did not follow vocal fold vibration. Group 4 cells (n = 3) were active during inspiration between phonations. Group 5 cells (n = 4) showed both inspiratory and expiratory modulation. These results indicate that laryngeal afferent activity responds to phonation-specific events during vocalization. This stereotyped afferent information might be used by the central nervous system to modulate vocalization. PMID:11459373

Clark, K F; Farber, J P

2001-07-01

43

A Novel Cytokine Pathway Suppresses Glial Cell Melanogenesis after Injury to Adult Nerve  

OpenAIRE

The neural crest gives rise to numerous cell types, including Schwann cells, neurons, and melanocytes. The extent to which adult neural crest-derived cells retain plasticity has not been tested previously. We report that cutting adult mouse sciatic nerve induces pigmentation around nerve fascicles, among muscle bundles, and in the hypodermis. Pigmented cells are derived from adult nerve, because pigmentation occurs even when nerve fragments are grafted into tyrosinase null albino mice. Pigmen...

Rizvi, Tilat A.; Huang, Yuan; Sidani, Amer; Atit, Radhika; Largaespada, David A.; Boissy, Raymond E.; Ratner, Nancy

2002-01-01

44

Tirasemtiv amplifies skeletal muscle response to nerve activation in humans  

OpenAIRE

Introduction: In this study we tested the hypothesis that tirasemtiv, a selective fast skeletal muscle troponin activator that sensitizes the sarcomere to calcium, could amplify the response of muscle to neuromuscular input in humans. Methods: Healthy men received tirasemtiv and placebo in a randomized, double-blind, 4-period, crossover design. The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot. The force–freq...

Hansen, Richard; Saikali, Khalil G.; Chou, Willis; Russell, Alan J.; Chen, Michael M.; Vijayakumar, Vipin; Stoltz, Randall R.; Baudry, Stephane; Enoka, Roger M.; Morgans, David J.; Wolff, Andrew A.; Malik, Fady I.

2014-01-01

45

Anti-Apoptotic Proteins in Nerve Cell Survival and Neurodegeneration  

OpenAIRE

Apoptosis is a genetically regulated cell death program, which shows distinct morphological characteristics. It takes place during neuronal development and in some neurodegenerative diseases. During apoptosis, the intracellular proteins are degraded by various caspases, cysteine aspartases, which are regulated by pro- and anti-apoptotic signals. This thesis elucidates the role of anti-apoptotic proteins in nerve cell survival and neurodegeneration. Studies have focused on Bcl-2 family members...

Korhonen, Laura

2002-01-01

46

Fast optical response to electrical activation in peripheral nerves  

Science.gov (United States)

Complex neuronal structures and interactions make studying fast optical signals associated with brain activation difficult, especially in non-invasive measurements that are further complicated by the filtering effect of the scalp and skull. We have chosen to study fast optical signals in the peripheral nervous system to look at a more simplified biological neuronal structure and a system that is more accessible to non-invasive optical studies. In this study, we recorded spatially resolved electrical and optical responses of the human sural nerve to electrical stimulation. A 0.1 ms electrical stimulation was used to activate the sural nerve. Electrical signals were collected by an electromyogram machine and results showed an electrical response spanning a distance of 8 mm across the nerve. Optical signals were collected by a two-wavelength (690 and 830 nm) near-infrared spectrometer and displayed a characteristic decrease in intensity at both wavelengths. Data were taken at multiple positions and then reproduced five times. The average optical data over the five trials showed an optical signal that was spatially consistent with the electrical response to sural nerve stimulation.

Chen, Debbie K.; Tong, Yunjie; Sassaroli, Angelo; Bergethon, Peter R.; Fantini, Sergio

2007-02-01

47

Localization and control of activity in peripheral nerves.  

Science.gov (United States)

Interest in the field of the natural control of human limb using physiological signals has risen dramatically in the past 20 years due to the success of the brain machine interface. Cortical signals carry significant information but are difficult to access. The peripheral nerves of the body carry both command and sensory signals and are far more accessible. While numerous studies have documented the selective stimulation properties of, conventionally round, nerve cuff electrodes (i.e., transverse geometry) and even self-sizing electrodes, recording the activity levels from individual fascicles using these electrodes is still an unsolved problem. Moreover, the control algorithms for the control of joint movement with multiple contact electrodes such as the flat interface nerve electrode (FINE) have been difficult to implement. We propose solutions to both these problems by using beam forming techniques to detect the location and the activity in various fascicles. We also developed a control algorithm that separates the dynamic from the passive properties to solve the redundancy problem in multiple joint problems. This techniques could find application in the natural control of artificial limbs from peripheral nerve signals for patients with amputated limbs or to restore function in patients with stroke or paralyzed limbs. PMID:19163426

Durand, D M; Park, H J; Wodlinger, B

2008-01-01

48

Bilateral peripheral neural activity observed in vivo following unilateral nerve injury  

OpenAIRE

Manganese-enhanced magnetic resonance imaging (MRI) is a surrogate method to measure calcium content in nervous system since manganese physiologically follows calcium. Manganese is detectable in MRI and therefore visualizes structures and cell populations that actively regulate calcium. Since calcium is actively recruited for the transmission of action potentials, our purpose is to validate manganese-enhanced MRI for detection of changes in lumbar nerves related to nociception. A neuropathic ...

Behera, Deepak; Behera, Subrat; Jacobs, Kathleen E.; Biswal, Sandip

2013-01-01

49

Peripheral nerve regeneration after experimental section in ovine radial and tibial nerves using synthetic nerve grafts, including expanded bone marrow mesenchymal cells: morphological and neurophysiological results.  

Science.gov (United States)

The standard treatment of peripherical nerve injuries with substance gap is to introduce the nerve free extremes in a biodegradable tube which, as a biocamera, allows the continuity of the nerve, promote the neuroconduction and save the lesion from the surrounding fibrosis. However, this procedure has not any direct effect on the neuroregeneration nor to resolve high severe lesions. The mesenchymal stem cells (MSC) can derivate "in vitro" in different lineages, including Schwann cells. Different studies have shown MSC can promote the nerve regeneration in rodents, dogs and primates. Moving to the human clinical application requires the procedure standardization, including the optimal cell dose which we have to use. In the sheep model animal we performed a study of 1 cm. nerve section-ressection and repair with a Neurolac™ biocamera, in whose gap we applied between 30 to 50×10(6) MSC from cancellous bone, all of them selected and cultured with GMP procedures. The results were compared with controls (saline serum ± platelet-rich plasma). We used radial nerve (sensitive) and tibial nerve (motor) from 7 sheep. In the first step we performed the surgical lesion and bone marrow aspiration, and in 3 weeks we performed the surgical repair. 3 sheep were sacrificed in 3 months, and 4 sheep in 6 months. In all surgeries we performed a neurophysiological register. When we obtained the tissue samples, we performed an histological, immunohistiquimical and morphometrical study. The recovery percentage was defined comparing the axonal density from the proximal and distal lesion margins. The 3 months samples results were wrong. In 6 months samples results we observed a significative myelined nervous fibers and conduction increasing, in front of controls, both radial and tibial nerves. These results suggest the MSC application in biodegradable scaffold in nerve injuries promotes good results in terms of regeneration and functional recovery. PMID:25384470

Casañas, Joaquim; de la Torre, Jaime; Soler, Francesc; García, Felix; Rodellar, Clementina; Pumarola, Martí; Climent, Jana; Soler, Robert; Orozco, Lluís

2014-10-01

50

Central cholinergic activation of a vagus nerve-to-spleen circuit alleviates experimental colitis.  

Science.gov (United States)

The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through ?7 nicotinic acetylcholine receptor (?7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and ?7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility complex II level and pro-inflammatory cytokine secretion by splenic CD11c? cells mediated by ?7nAChR signaling. The cholinergic anti-inflammatory efficacy was abolished in mice with vagotomy, splenic neurectomy, or splenectomy. In conclusion, central cholinergic activation of a vagus nerve-to-spleen circuit controls intestinal inflammation and this regulation can be explored to develop novel therapeutic strategies. PMID:23881354

Ji, H; Rabbi, M F; Labis, B; Pavlov, V A; Tracey, K J; Ghia, J E

2014-03-01

51

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

OpenAIRE

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.

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

2011-01-01

52

Changes in afferent impulse activity of small intestine mesenteric nerves in response to antigen challenge.  

Science.gov (United States)

Sprague-Dawley rats (weight 130-150 g) were sensitized by an intraperitoneal injection of 1 mg chicken egg albumin with 0.25 ml Freund's adjuvant to stimulate immunoglobulin E antibody production. Leukocyte migration inhibitory factor was used as an indicator of animal sensitization. In acute electrophysiological experiments on sensitized animals, an intra-arterial or intraluminal chicken egg albumin (100 microg) challenge evoked a 10% enhancement of the activity of mesenteric nerves of the small intestine, regardless of the injection site chosen. Afferent nerve activity in control animals was not changed during the chicken egg albumin challenge. Morphometry at the light microscope level showed activation of mast cell degranulation after the antigen challenge to presensitized rats. Intraluminal injections of a stimulator of mast cell degranulation, compound 48/80 (20-30 mg), were found to increase afferent discharges in intact rats. An antagonist of H1 histamine receptors, clemastine, reduced the effect of compound 48/80. The results obtained provide direct evidence for the stimulation of sensory nerve endings by mast cell mediators released during mast cell degranulation. PMID:10625072

Nozdrachev, A D; Akoev, G N; Filippova, L V; Sherman, N O; Lioudyno, M I; Makarov, F N

1999-01-01

53

Nerve cell markers in ossifying fibromyxoid tumour of soft parts.  

Science.gov (United States)

Reported herein are two benign ossifying fibromyxoid tumors (OFMTs) of the soft tissues in axilla and terminal phalanx respectively. Both cases on immunohistochemistry (IHC) showed reactivity for vimentin, S-100 protein and glial fibrillary acidic protein (GFAP) antibodies. In addition, a focal/diffuse strong positivity for neurofilament (NF) and neuron specific enolase (NSE) was observed. Electron microscopy in one instance revealed abundant intermediate filaments, primitive cell junctions and a focally present external lamina. In the light of nerve cell differentiation of these tumors and the similarity of IHC profile and EM features of OFMT to a poorly differentiated malignant peripheral nerve sheath tumor (MPNST); it is suggested that OFMT is a variably differentiated PNST rather than a simple Schwannian neoplasm as is believed. PMID:11883138

Shet, T; Desai, S; Kane, S; Vora, I

2001-04-01

54

Advances in recording scattered light changes in crustacean nerve with electrical activation  

Energy Technology Data Exchange (ETDEWEB)

We investigated optical changes associated with crustacean nerve stimulation using birefringent and large angle scattered light. Improved detection schemes disclosed high temporal structure of the optical signals and allowed further investigations of biophysical mechanisms responsible for such changes. Most studies of physiological activity in neuronal tissue use techniques that measure the electrical behavior or ionic permeability of the nerve, such as voltage or ion sensitive dyes injected into cells, or invasive electric recording apparatus. While these techniques provide high resolution, they are detrimental to tissue and do not easily lend themselves to clinical applications in humans. Electrical and chemical components of neural excitation evoke physical responses observed through changes in scattered and absorbed light. This method is suited for in-vivo applications. Intrinsic optical changes have shown themselves to be multifaceted in nature and point to several different physiological processes that occur with different time courses during neural excitation. Fast changes occur concomitantly with electrical events, and slow changes parallel metabolic events including changes in blood flow and oxygenation. Previous experiments with isolated crustacean nerves have been used to study the biophysical mechanisms of fast optical changes. However, they have been confounded by multiple superimposed action potentials which make it difficult to discriminate the temporal signatures of individual optical responses. Often many averages were needed to adequately resolve the signal. More recently, optical signals have been observed in single trials. Initially large angle scattering measurements were used to record these events with much of the signal coming from cellular swelling associated with water influx during activation. By exploiting the birefringent properties derived from the molecular stiucture of nerve membranes, signals appear larger with a greater contrast, but direct comparison of birefringent and 90{sup o} scattering signals has not been reported. New developments in computer and optical technology allow optical recording with higher temporal resolution than could be achieved previously. This has led us to undertake more detailed studies of the biophysical mechanisms underlying these transient changes. Optimization of this technology in conjunction with other technical developments presents a path to noninvasive dynamic clinical observation of optical responses. To conduct these optical recordings, we placed dissected leg, claw and ventral cord nerves from crayfish and lobster in a recording chamber constructed from black Delrin. The chamber consisted of several wells situated perpendicularly to the long axis of the nerve that could beelectrically isolated for stimulating and recording electrical activation, and a window in the center for optical measurements. To measure the birefringence from the nerve, light from a 120W halogen bulb was focused onto the nerve from below the window through a 10X microscope objective and polarized at a 45 degree angle with respect to the long axis of the nerve bundle. A second polarizer turned 90 degrees with respect to the first polarizer was placed on top of the chamber and excluded direct source illumination, passing only birefringent light from the nerve. A large area photodiode placed directly on top of the polarizer detected the magnitude of the birefringent light. To measure light scattered 90 degrees by the nerve, a short length of image conduit placed perpendicularly to the nerve directed large angle scattered light from the nerve to a second photodiode. The output of each photodiode was amplified by a first stage amplifier which produced a DC level output, and was coupled to an AC amplifier (0.3 Hz High Pass) with a gain of 1000 to optimally record changes across time.

Carter, K. M. (Kathleen M.); Rector, D. M. (David M.); Martinez, A. T. (Anne T.); Guerra, F. M. (Francisco M.); George, J. S. (John S.)

2002-01-01

55

The terminal nerve ganglion cells project to the olfactory mucosa in the dwarf gourami.  

Science.gov (United States)

Single- and double-label immunocytochemical studies were conducted using antisera to salmon gonadotropin-releasing hormone (sGnRH) and molluscan cardioexcitatory peptide (FMRFamide) to determine whether terminal nerve ganglion cells project to the olfactory mucosa in the dwarf gourami, Colisa lalia. Both peptides were present in terminal nerve ganglion perikarya and fibers in brain and nasal cavity. Labeled fibers were present in the olfactory nerve and could be traced to the olfactory mucosa. All terminal nerve ganglion cells contained both sGnRH and FMRFamide-like peptides. This study suggests that the terminal nerve ganglion cells can influence both brain and chemoreceptive structures. PMID:12413662

Wirsig-Wiechmann, Celeste R; Oka, Yoshitaka

2002-11-01

56

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

Science.gov (United States)

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

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

2014-11-01

57

Nerve growth factor stimulates protein tyrosine phosphorylation in PC-12 pheochromocytoma cells.  

OpenAIRE

The cellular actions of nerve growth factor (NGF) and epidermal growth factor (EGF) may be mediated by changes in protein phosphorylation. The tyrosine phosphorylation of two predominant proteins of molecular mass 40 and 42 kDa is seen in PC-12 cells treated with NGF or EGF, correlating with activation of a previously identified serine/threonine protein kinase that phosphorylates microtubule-associated protein (MAP). Stimulation of phosphoprotein (pp) 40 and 42 phosphorylation and MAP kinase ...

Miyasaka, T.; Sternberg, D. W.; Miyasaka, J.; Sherline, P.; Saltiel, A. R.

1991-01-01

58

Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals. Results As previously reported we found that the WldS mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that WldS transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in WldS and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in WldS transgenic rats. Conclusions RGC axon regeneration is similar between WldS transgenic and wildtype rats, but WldS transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the WldS protein.

Lorber Barbara

2012-06-01

59

Afferent vagal nerve stimulation resets baroreflex neural arc and inhibits sympathetic nerve activity.  

Science.gov (United States)

It has been established that vagal nerve stimulation (VNS) benefits patients and/or animals with heart failure. However, the impact of VNS on sympathetic nerve activity (SNA) remains unknown. In this study, we investigated how vagal afferent stimulation (AVNS) impacts baroreflex control of SNA. In 12 anesthetized Sprague-Dawley rats, we controlled the pressure in isolated bilateral carotid sinuses (CSP), and measured splanchnic SNA and arterial pressure (AP). Under a constant CSP, increasing the voltage of AVNS dose dependently decreased SNA and AP. The averaged maximal inhibition of SNA was -28.0 ± 10.3%. To evaluate the dynamic impacts of AVNS on SNA, we performed random AVNS using binary white noise sequences, and identified the transfer function from AVNS to SNA and that from SNA to AP. We also identified transfer functions of the native baroreflex from CSP to SNA (neural arc) and from SNA to AP (peripheral arc). The transfer function from AVNS to SNA strikingly resembled the baroreflex neural arc and the transfer functions of SNA to AP were indistinguishable whether we perturbed ANVS or CSP, indicating that they likely share common central and peripheral neural mechanisms. To examine the impact of AVNS on baroreflex, we changed CSP stepwise and measured SNA and AP responses with or without AVNS. AVNS resets the sigmoidal neural arc downward, but did not affect the linear peripheral arc. In conclusion, AVNS resets the baroreflex neural arc and induces sympathoinhibition in the same manner as the control of SNA and AP by the native baroreflex. PMID:25194023

Saku, Keita; Kishi, Takuya; Sakamoto, Kazuo; Hosokawa, Kazuya; Sakamoto, Takafumi; Murayama, Yoshinori; Kakino, Takamori; Ikeda, Masataka; Ide, Tomomi; Sunagawa, Kenji

2014-09-01

60

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

Directory of Open Access Journals (Sweden)

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.

A.K. Sheikhi

2007-01-01

61

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

OpenAIRE

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...

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

62

Photodynamic damage of glial cells in crayfish ventral nerve cord  

Science.gov (United States)

Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

2011-03-01

63

Satellite Glial Cell Proliferation in the Trigeminal Ganglia After Chronic Constriction Injury of the Infraorbital Nerve  

OpenAIRE

We have examined satellite glial cell (SGC) proliferation in trigeminal ganglia following chronic constriction injury of the infraorbital nerve. Using BrdU labeling combined with immunohistochemistry for SGC specific proteins we positively confirmed proliferating cells to be SGCs. Proliferation peaks at approximately 4 days after injury and dividing SGCs are preferentially located around neurons that are immunopositive for ATF-3, a marker of nerve injury. After nerve injury there is an increa...

Donegan, Macayla; Kernisant, Melanie; Cua, Criselda; Jasmin, Luc; Ohara, Peter T.

2013-01-01

64

Laser-activated adhesive films for sutureless median nerve anastomosis.  

Science.gov (United States)

A novel chitosan adhesive film that incorporates the dye 'Rose Bengal' (RB) was used in conjunction with a green laser to repair transected rat median nerves in vivo. Histology and electrophysiological recording assessed the impact of the laser-adhesive technique on nerves. One week post-operatively, the sham-control group (laser-adhesive technique applied on un-transected nerves) conserved the average number and size of myelinated fibres in comparison to its contralateral side and electrophysiological recordings demonstrated no significant difference with un-operated nerves. Twelve weeks after the laser-adhesive anastomoses, nerves were in continuity with regenerated axons that crossed the anastomotic site. PMID:23712961

Barton, Mathew; Morley, John W; Stoodley, Marcus A; Ng, Kheng-Seong; Piller, Sabine C; Duong, Hong; Mawad, Damia; Mahns, David A; Lauto, Antonio

2013-12-01

65

BLOOD PRESSURE REGULATION IN HUMANS: CALCULATION OF AN “ERROR SIGNAL” IN CONTROL OF SYMPATHETIC NERVE ACTIVITY  

OpenAIRE

Within an individual, diastolic blood pressure is negatively related to sympathetic burst incidence such that lower pressure is associated with high burst incidence. Our goal was to explore the utility of a calculation of a diastolic blood pressure “error signal” in the control of muscle sympathetic nerve activity in men and women. Baseline muscle sympathetic nerve activity was measured in healthy young men (n=22) and women (n=28). Women had significantly lower muscle sympathetic nerve ac...

Wehrwein, Erica A.; Joyner, Michael J.; Hart, Emma Cj; Wallin, B. Gunnar; Karlsson, Tomas; Charkoudian, Nisha

2009-01-01

66

Sympathetic nerve activity and simulated diving in healthy humans.  

Science.gov (United States)

The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome. PMID:24368150

Shamsuzzaman, Abu; Ackerman, Michael J; Kuniyoshi, Fatima Sert; Accurso, Valentina; Davison, Diane; Amin, Raouf S; Somers, Virend K

2014-04-01

67

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.)

68

Activity-Based Protein Profiling Reveals Broad Reactivity of the Nerve Agent Sarin.  

Science.gov (United States)

Elucidation of noncholinesterase protein targets of organophosphates, and nerve agents in particular, may reveal additional mechanisms for their high toxicity as well as clues for novel therapeutic approaches toward intoxications with these agents. Within this framework, we here describe the synthesis of the activity-based probe 3, which contains a phosphonofluoridate moiety, a P-Me moiety, and a biotinylated O-alkyl group, and its use in activity-based protein profiling with two relevant biological samples, that is, rhesus monkey liver and cultured human A549 lung cells. In this way, we have unearthed eight serine hydrolases (fatty acid synthase, acylpeptide hydrolase, dipeptidyl peptidase 9, prolyl oligopeptidase, carboxylesterase, long-chain acyl coenzyme A thioesterase, PAF acetylhydrolase 1b, and esterase D/S-formyl glutathione hydrolase) as targets that are modified by the nerve agent sarin. It is also shown that the newly developed probe 3 might find its way into the development of alternative, less laborious purification protocols for human butyrylcholinesterase, a potent bioscavenger currently under clinical investigation as a prophylactic/therapeutic for nerve agent intoxications. PMID:19226147

Tuin, Adriaan W; Mol, Marijke A E; van den Berg, Roland M; Fidder, A; van der Marel, Gijs A; Overkleeft, Herman S; Noort, Daan

2009-02-18

69

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

KAUST Repository

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.

Takaku, Yasuharu

2014-01-07

70

Sericin protects against diabetes-induced injuries in sciatic nerve and related nerve cells?  

OpenAIRE

Sericin from discarded silkworm cocoons of silk reeling has been used in different fields, such as cosmetology, skin care, nutrition, and oncology. The present study established a rat model of type 2 diabetes by consecutive intraperitoneal injections of low-dose (25 mg/kg) streptozotocin. After intragastrical perfusion of sericin for 35 days, blood glucose levels significantly declined, and the expression of neurofilament protein in the sciatic nerve and nerve growth factor in L4–6 spinal g...

Song, Chengjun; Yang, Zhenjun; Zhong, Meirong; Chen, Zhihong

2013-01-01

71

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

Science.gov (United States)

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

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

72

Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury.  

Science.gov (United States)

Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits, culture-expanded and differentiated into Schwann cell-like cells. Autologous platelet-rich plasma and Schwann cell-like cells were mixed in suspension at a density of 1 × 10(6) cells/mL, prior to introduction into a poly (lactic-co-glycolic acid) conduit. Fabricated tissue-engineered nerves were implanted into rabbits to bridge 10 mm sciatic nerve defects (platelet-rich plasma group). Controls were established using fibrin as the seeding matrix for Schwann cell-like cells at identical density to construct tissue-engineered nerves (fibrin group). Twelve weeks after implantation, toluidine blue staining and scanning electron microscopy were used to demonstrate an increase in the number of regenerating nerve fibers and thickness of the myelin sheath in the platelet-rich plasma group compared with the fibrin group. Fluoro-gold retrograde labeling revealed that the number of Fluoro-gold-positive neurons in the dorsal root ganglion and the spinal cord anterior horn was greater in the platelet-rich plasma group than in the fibrin group. Electrophysiological examination confirmed that compound muscle action potential and nerve conduction velocity were superior in the platelet-rich plasma group compared with the fibrin group. These results indicate that autologous platelet-rich plasma gel can effectively serve as a seeding matrix for Schwann cell-like cells to construct tissue-engineered nerves to promote peripheral nerve regeneration. PMID:25538751

Ye, Fagang; Li, Haiyan; Qiao, Guangxi; Chen, Feng; Tao, Hao; Ji, Aiyu; Hu, Yanling

2012-10-15

73

Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme  

OpenAIRE

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were...

Hemmert, Andrew C.; Otto, Tamara C.; Chica, Roberto A.; Wierdl, Monika; Edwards, Jonathan S.; Lewis, Steven L.; Edwards, Carol C.; Tsurkan, Lyudmila; Cadieux, C. Linn; Kasten, Shane A.; Cashman, John R.; Mayo, Stephen L.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

2011-01-01

74

Nerve pathways involved in adrenergic regulation of electrical and mechanical activities in the chicken rectum.  

OpenAIRE

Peripheral nerve pathways responsible for adrenergic inhibition of mechanical and electrical activities in the chicken rectum and receptors mediating the adrenergic inhibition were investigated in isolated extrinsically-innervated rectum of the chicken. Electrical stimulation of the anal end (Ra) or the ileal cut end (Ri) of Remak's nerve, or perivascular nerves (P) elicited relaxation of the rectum pretreated with atropine (0.5 microM) and hexamethonium (0.3 mM) to block the cholinergic and ...

Komori, S.; Ohashi, H.

1987-01-01

75

Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration  

OpenAIRE

Peripheral nerve injuries and neuropathies lead to profound functional deficits. Here, we have demonstrated that muscle-derived stem/progenitor cells (MDSPCs) isolated from adult human skeletal muscle (hMDSPCs) can adopt neuronal and glial phenotypes in vitro and ameliorate a critical-sized sciatic nerve injury and its associated defects in a murine model. Transplanted hMDSPCs surrounded the axonal growth cone, while hMDSPCs infiltrating the regenerating nerve differentiated into myelinating ...

Lavasani, Mitra; Thompson, Seth D.; Pollett, Jonathan B.; Usas, Arvydas; Lu, Aiping; Stolz, Donna B.; Clark, Katherine A.; Sun, Bin; Pe?ault, Bruno; Huard, Johnny

2014-01-01

76

Intravenous Transplantation of Mesenchymal Stromal Cells to Enhance Peripheral Nerve Regeneration  

OpenAIRE

Peripheral nerve injury is a common and devastating complication after trauma and can cause irreversible impairment or even complete functional loss of the affected limb. While peripheral nerve repair results in some axonal regeneration and functional recovery, the clinical outcome is not optimal and research continues to optimize functional recovery after nerve repair. Cell transplantation approaches are being used experimentally to enhance regeneration. Intravenous infusion of mesenchymal s...

Matthes, Stella M.; Kerstin Reimers; Insa Janssen; Christina Liebsch; Kocsis, Jeffery D.; Vogt, Peter M.; Christine Radtke

2013-01-01

77

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)

All transforming growth factor beta (TGF-beta) 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-betas 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-betas 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

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

2005-07-01

78

Effect of cervical sympathetic trunk transection on renal sympathetic nerve activity in rats.  

Science.gov (United States)

Stellate ganglion blockade (SGB) with a local anesthetic increases muscle sympathetic nerve activity in the tibial nerve in humans. However, whether this sympathetic excitation in the tibial nerve is due to a sympathetic blockade in the neck itself, or due to infiltration of a local anesthetic to adjacent nerves including the vagus nerve remains unknown. To rule out one mechanism, we examined the effects of cervical sympathetic trunk transection on renal sympathetic nerve activity (RSNA) in anesthetized rats. Seven rats were anesthetized with intraperitoneal urethane. RSNA together with arterial blood pressure and heart rate were recorded for 15 min before and 30 min after left cervical sympathetic trunk transection. The baroreceptor unloading RSNA obtained by decreasing arterial blood pressure with administration of sodium nitroprusside was also measured. Left cervical sympathetic trunk transection did not have any significant effects on RSNA, baroreceptor unloading RSNA, arterial blood pressure, and heart rate. These data suggest that there was no compensatory increase in RSNA when cervical sympathetic trunk was transected and that the increase in sympathetic nerve activity in the tibial nerve during SGB in humans may result from infiltration of a local anesthetic to adjacent nerves rather than a sympathetic blockade in the neck itself. PMID:18198983

Ikeda, T; Hirakawa, H; Kemuriyama, T; Nishida, Y; Kazama, T

2009-01-01

79

Reduced spontaneous sympathetic nerve activity in multiple sclerosis patients.  

Science.gov (United States)

For the first time, we obtained direct intra-neural measurements of muscle sympathetic nerve activity (MSNA) in relapsing-remitting multiple sclerosis (MS) patients to test the hypothesis that spontaneous resting MSNA is reduced in MS patients compared to age, sex-matched healthy controls. Spontaneous MSNA (microneurography; peroneal nerve), plasma norepinephrine, arterial blood pressure (finger photoplethysmography), and heart rate were measured at rest in three groups: 1) relapsing-remitting MS patients on disease modifying therapy only (MS-DT; n=6); 2) relapsing-remitting MS patients on disease modifying therapy and medications for MS-related symptoms that are known to effect the central nervous system (MS-DT/ST; n=5), and 3) healthy age and sex-matched controls (CON; n=6). Compared to the CON group, MSNA burst frequency (bursts/min) was significantly lower in both MS-DT (P=0.027) and MS-DT/ST groups (P=0.003). Similarly, MSNA burst incidence (bursts/100 heartbeats) was significantly reduced in both MS-DT (P=0.049) and MS-DT/ST groups (P=0.004) compared to the CON group. Burst frequency and burst incidence were not different between MS-DT and MS-DT/ST groups. Resting plasma norepinephrine was also significantly lower in both MS-DT (P=0.039) and MS-DT/ST groups (P=0.021) compared to the CON group. Reduced MSNA may signify an important dysfunction in autonomic control of cardiovascular function in patients with MS. PMID:25034056

Keller, David M; Fadel, Paul J; Harnsberger, Melissa A; Remington, Gina M; Frohman, Elliot M; Davis, Scott L

2014-09-15

80

Binding and internalization of nerve growth factor by PC12 cells  

International Nuclear Information System (INIS)

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). 125I-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

81

Advantage of recording single-unit muscle sympathetic nerve activity in heart failure  

OpenAIRE

Elevated sympathetic activation is a characteristic feature of heart failure (HF). Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA) by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow ...

HISAYOSHIMURAI

2012-01-01

82

Activation of calcium-dependent potassium channels in rat brain neurons by neurotrophin-3 and nerve growth?factor  

OpenAIRE

The neurotrophins are signaling factors that are essential for survival and differentiation of distinct neuronal populations during the development and regeneration of the nervous system. The long-term effects of neurotrophins have been studied in detail, but little is known about their acute effects on neuronal activity. Here we use permeabilized whole-cell patch clamp to demonstrate that neurotrophin-3 (NT-3) and nerve growth factor activate calcium-dependent, paxilline-sensitive potassium ...

Holm, Ninna?R; Christophersen, Palle; Olesen, Søren?P; Gammeltoft, Steen

1997-01-01

83

Activation of MAPK ERK in peripheral nerve after injury  

OpenAIRE

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 satelli...

Tanomsridejchai N; Kaewsema A; Agthong S; Chentanez V

2006-01-01

84

Obesity-induced increases in sympathetic nerve activity: Sex matters.  

Science.gov (United States)

Abundant evidence obtained largely from male human and animal subjects indicates that obesity increases sympathetic nerve activity (SNA), which contributes to hypertension development. However, recent studies that included women reported that the strong relationships between muscle SNA and waist circumference or body mass index (BMI) found in men are not present in overweight and obese women. A similar sex difference in the association between adiposity and hypertension development has been identified in animal models of obesity. In this brief review, we consider two possible mechanisms for this sex difference. First, visceral adiposity, leptin, insulin, and angiotensin II have been identified as potential culprits in obesity-induced sympathoexcitation in males. We explore if these factors wield the same impact in females. Second, we consider if sex differences in vascular reactivity to sympathetic activation contribute. Our survey of the literature suggests that premenopausal females may be able to resist obesity-induced sympathoexcitation and hypertension in part due to differences in adipose disposition as well as its muted inflammatory response and reduced production of pressor versus depressor components of the renin-angiotensin system. In addition, vascular responsiveness to increased SNA may be reduced. However, more importantly, we identify the urgent need for further study, not only of sex differences per se, but also of the mechanisms that may mediate these differences. This information is required not only to refine treatment options for obese premenopausal women but also to potentially reveal new therapeutic avenues in obese men and women. PMID:25435000

Brooks, Virginia L; Shi, Zhigang; Holwerda, Seth W; Fadel, Paul J

2015-01-01

85

Role of macrophage migration inhibitory factor (MIF) in peripheral nerve regeneration: anti-MIF antibody induces delay of nerve regeneration and the apoptosis of Schwann cells.  

OpenAIRE

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine involved in inflammation and immune responses as well as in cell growth. Although we previously demonstrated the presence of MIF in peripheral nerves, and MIF mRNA expression was up-regulated after axotomy, the role of MIF in nerve injury and regeneration has not been evaluated. MATERIALS AND METHODS: To examine the potential role of MIF in nerve regeneration, we locally administered an anti-MIF polyclonal anti...

Nishio, Yasuhiko; Nishihira, Jun; Ishibashi, Teruo; Kato, Hiroyuki; Minami, Akio

2002-01-01

86

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

OpenAIRE

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...

Mantovani, Cristina; Terenghi, Giorgio; Magnaghi, Valerio

2014-01-01

87

Effects of nerve growth factor on X-irradiated reaggregation cultures of rat brain cells  

Energy Technology Data Exchange (ETDEWEB)

The effects of exogenously added nerve growth factor (NGF) on reaggregation cultures of foetal rat brain cells after X-irradiation with 2 Gy were studied. Irradiation caused decreased protein and DNA levels, which was not prevented by NGF. The activities of the cholinergic marker enzymes choline acetyl transferase and acetylcholine esterase were increased in irradiated cultures. However, no difference in the activities of these enzymes was found between irradiated and unirradiated NGF-treated cultures. Irradiation did not affect the activity of the marker enzyme for oligodendrocytes (2',3'-cyclic nucleotide 3'-phosphodiesterase), but caused an increase in the astrocyte marker (glutamine synthetase) activity. This effect on astrocytes was prevented by NGF. (Author).

Dimberg, Y. (Swedish Univ. of Agricultural Sciences, Uppsala (Sweden)); Aspberg, A.; Tottmar, O. (Uppsala Univ. (Sweden). Dept. of Zoophysiology)

1993-12-01

88

Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2.  

OpenAIRE

BACKGROUND and AIMS: The vagus nerve negatively regulates macrophage cytokine production via the release of acetylcholine (ACh) and activation of nicotinic acetylcholine receptors (nAChR). In various models of intestinal inflammation, vagus nerve efferent stimulation ameliorates disease. Given the actively constrained cytokine responses of intestinal macrophages, we explored the effect of nAChR activation on endocytosis and phagocytosis by macrophages residing in the peritoneal and mucosal co...

Zanden, Ep; Snoek, Sa; Heinsbroek, Se; Stanisor, Oi; Verseijden, C.; Boeckxstaens, Ge; Peppelenbosch, Mp; Greaves, Dr; Gordon, S.; Jonge, Wj

2009-01-01

89

A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown. Results Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF, which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain. Conclusions Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

Sakamoto Atsuhiro

2011-01-01

90

Segmental origins of cardiac sympathetic nerve activity in rats.  

Science.gov (United States)

The segmental origins of cardiac sympathetic nerve activity (CSNA) were investigated in 8 urethane-anesthetized, artificially ventilated rats. The left upper thoracic sympathetic chain was exposed retropleurally after removing the heads of the second to fourth ribs. The preganglionic inputs to the chain from segments T1-T3 and the trunk distal to T3 were marked for later sectioning. CSNA was recorded conventionally, amplified, rectified and smoothed. Its mean level was quantified before and after each preganglionic input was cut, usually in rostro-caudal sequence. The level after all inputs were cut (i.e. noise and residual ECG pickup) was subtracted from previous measurements. The signal decrement from cutting each preganglionic input was then calculated as a percentage. CSNA in all rats depended on preganglionic drive from two or more segments, which were not always contiguous. Over the population, most preganglionic drive came from T3 and below, while the least came from T1. But there was striking inter-individual variation, such that the strongest drive to CSNA in any one rat could come from T1, T2, T3, or below T3. These findings provide new functional data on the segmental origins of CSNA in rats. PMID:25500376

Pracejus, Natasha H; Farmer, David G S; McAllen, Robin M

2015-01-01

91

Effect of morphine on sympathetic nerve activity in humans  

Science.gov (United States)

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.

Carter, Jason R.; Sauder, Charity L.; Ray, Chester A.

2002-01-01

92

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

LENUS (Irish Health Repository)

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.

Henry, F P

2012-06-01

93

Transplantation of olfactory ensheathing cells to evaluate functional recovery after peripheral nerve injury.  

Science.gov (United States)

Olfactory ensheathing cells (OECs) are neural crest cells which allow growth and regrowth of the primary olfactory neurons. Indeed, the primary olfactory system is characterized by its ability to give rise to new neurons even in adult animals. This particular ability is partly due to the presence of OECs which create a favorable microenvironment for neurogenesis. This property of OECs has been used for cellular transplantation such as in spinal cord injury models. Although the peripheral nervous system has a greater capacity to regenerate after nerve injury than the central nervous system, complete sections induce misrouting during axonal regrowth in particular after facial of laryngeal nerve transection. Specifically, full sectioning of the recurrent laryngeal nerve (RLN) induces aberrant axonal regrowth resulting in synkinesis of the vocal cords. In this specific model, we showed that OECs transplantation efficiently increases axonal regrowth. OECs are constituted of several subpopulations present in both the olfactory mucosa (OM-OECs) and the olfactory bulbs (OB-OECs). We present here a model of cellular transplantation based on the use of these different subpopulations of OECs in a RLN injury model. Using this paradigm, primary cultures of OB-OECs and OM-OECs were transplanted in Matrigel after section and anastomosis of the RLN. Two months after surgery, we evaluated transplanted animals by complementary analyses based on videolaryngoscopy, electromyography (EMG), and histological studies. First, videolaryngoscopy allowed us to evaluate laryngeal functions, in particular muscular cocontractions phenomena. Then, EMG analyses demonstrated richness and synchronization of muscular activities. Finally, histological studies based on toluidine blue staining allowed the quantification of the number and profile of myelinated fibers. All together, we describe here how to isolate, culture, identify and transplant OECs from OM and OB after RLN section-anastomosis and how to evaluate and analyze the efficiency of these transplanted cells on axonal regrowth and laryngeal functions. PMID:24637657

Guerout, Nicolas; Paviot, Alexandre; Bon-Mardion, Nicolas; Honoré, Axel; Obongo, Rais; Duclos, Célia; Marie, Jean-Paul

2014-01-01

94

Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice  

International Nuclear Information System (INIS)

In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimensizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab

95

Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells.  

Science.gov (United States)

Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas able to grow under conditions of metabolic stress caused by insufficient nutrients or oxygen. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and activity-dependent neuroprotective protein (ADNP) have glioprotective potential. However, whether PACAP/ADNP signaling is involved in the resistance to cell death in MPNST cells remains to be clarified. Here, we investigated the involvement of this signaling system in the survival response of MPNST cells against hydrogen peroxide (H(2)O(2))-evoked death both in the presence of normal serum (NS) and in serum-starved (SS) cells. Results showed that ADNP levels increased time-dependently (6-48 h) in SS cells. Treatment with PACAP38 (10(-9) to 10(-5) M) dose-dependently increased ADNP levels in NS but not in SS cells. PAC(1)/VPAC receptor antagonists completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP expression in SS cells. NS-cultured cells exposed to H(2)O(2) showed significantly reduced cell viability (~50 %), increased p53 and caspase-3, and DNA fragmentation, without affecting ADNP expression. Serum starvation significantly reduced H(2)O(2)-induced detrimental effects in MPNST cells, which were not further ameliorated by PACAP38. Altogether, these finding provide evidence for the involvement of an endogenous PACAP-mediated ADNP signaling system that increases MPNST cell resistance to H(2)O(2)-induced death upon serum starvation. PMID:22454142

Castorina, Alessandro; Giunta, Salvatore; Scuderi, Soraya; D'Agata, Velia

2012-11-01

96

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

2002-10-01

97

Muscle sympathetic nerve activity and hemodynamic alterations in middle-aged obese women  

OpenAIRE

To study the relationship between the sympathetic nerve activity and hemodynamic alterations in obesity, we simultaneously measured muscle sympathetic nerve activity (MSNA), blood pressure, and forearm blood flow (FBF) in obese and lean individuals. Fifteen normotensive obese women (BMI = 32.5 ± 0.5 kg/m²) and 11 age-matched normotensive lean women (BMI = 22.7 ± 1.0 kg/m²) were studied. MSNA was evaluated directly from the peroneal nerve by microneurography, FBF was measured by venous occ...

Ribeiro M.M.; Trombetta I.C.; Batalha L.T.; Rondon M.U.P.B.; Forjaz C.L.M.; Barretto A.C.P.; Villares S.M.F.; Negrão C.E.

2001-01-01

98

Relief of fecal incontinence by sacral nerve stimulation linked to focal brain activation  

DEFF Research Database (Denmark)

This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence.

Lundby, Lilli; MØller, Arne

2011-01-01

99

Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme  

Science.gov (United States)

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning. PMID:21445272

Hemmert, Andrew C.; Otto, Tamara C.; Chica, Roberto A.; Wierdl, Monika; Edwards, Jonathan S.; Lewis, Steven L.; Edwards, Carol C.; Tsurkan, Lyudmila; Cadieux, C. Linn; Kasten, Shane A.; Cashman, John R.; Mayo, Stephen L.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

2011-01-01

100

Bilateral mental nerve neuropathy in an adolescent during sickle cell crises.  

Science.gov (United States)

Mental nerve neuropathy causes the "numb chin" syndrome and is usually associated with mandibular bone injury or disease in adults. It has been reported in adults during sickle cell crises. We describe a 15-year-old boy who developed bilateral mental nerve neuropathies during a sickle cell crisis. This case is unusual because of the simultaneous bilateral involvement and because of the age. PMID:22290855

Hamdoun, Elwaseila; Davis, Lamar; McCrary, Sara Jane; Eklund, Neva Penton; Evans, Owen B

2012-08-01

101

Neural cell transplantation effects on sciatic nerve regeneration after a standardized crush injury in the rat.  

OpenAIRE

The goal of the present study was to assess whether in vitro-differentiated N1E-115 cells supported by a collagen membrane would enhance rat sciatic nerve regeneration after a crush injury. To set up an appropriate experimental model for investigating the effects of neural cell transplantation, we have recently described the sequence of functional and morphologic changes occurring after a standardized sciatic nerve crush injury with a nonserrated clamp. Functional recovery was evaluated using...

Fregnan, Federica; Geuna, Stefano

2008-01-01

102

Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.  

Science.gov (United States)

This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables. PMID:25002406

Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru

2014-10-01

103

Spike detection in human muscle sympathetic nerve activity using the kurtosis of stationary wavelet transform coefficients  

OpenAIRE

The accurate assessment of autonomic sympathetic function is important in the diagnosis and study of various autonomic and cardiovascular disorders. Sympathetic function in humans can be assessed by recording the muscle sympathetic nerve activity, which is characterized by synchronous neuronal discharges separated by periods of neural silence dominated by colored Gaussian noise. The raw nerve activity is generally rectified, integrated, and quantified using the integrated burst rate or area. ...

Brychta, Robert J.; Shiavi, Richard; Robertson, David; Diedrich, Andre?

2006-01-01

104

Relationship between muscle sympathetic nerve activity and aortic wave reflection characteristics in young men and women  

OpenAIRE

Increased arterial stiffness is associated with higher levels of aortic wave reflection and aortic blood pressure. Recent evidence suggests a link between muscle sympathetic nerve activity and indices of arterial stiffness. Therefore, the aims of this study were to examine 1) the relationship between resting muscle sympathetic nerve activity and characteristics of aortic pressure wave reflection, and 2) the influence of sex on these relationships. In forty-four subjects (23F/21M; 25 ± 1 year...

Casey, Darren P.; Curry, Timothy B.; Joyner, Michael J.; Charkoudian, Nisha; Hart, Emma C.

2011-01-01

105

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.

106

Autophagy Is Involved in the Reduction of Myelinating Schwann Cell Cytoplasm during Myelin Maturation of the Peripheral Nerve  

Science.gov (United States)

Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination. PMID:25581066

Jang, So Young; Shin, Yoon Kyung; Park, So Young; Park, Joo Youn; Rha, Seo-Hee; Kim, Jong Kuk; Lee, Hye Jeong; Park, Hwan Tae

2015-01-01

107

Nerve Impulses in Plants  

Science.gov (United States)

Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

Blatt, F. J.

1974-01-01

108

Organ-specific activation of the gastric branch of the efferent vagus nerve by ghrelin in urethane-anesthetized rats.  

Science.gov (United States)

Ghrelin plays multiple physiological roles such as growth hormone secretion and exerting orexigenic actions; however, its physiological roles in the electrical activity of autonomic nerves remain unclear. Here, we investigated the effects of human ghrelin on several autonomic nerve activities in urethane-anesthetized rats using an electrophysiological method. Intravenous injection of ghrelin at 3 ?g/kg significantly and transiently potentiated the efferent activity of the gastric vagus nerve; however, it did not affect the efferent activity of the hepatic vagus nerve. The activated response to ghrelin in the gastric efferent vagus nerve was not affected by the gastric afferent vagotomy, suggesting that this effect was not induced via the gastric afferent vagus nerve. Ghrelin did not affect the efferent activity of the brown adipose tissue, adrenal gland sympathetic nerve, and the renal sympathetic nerve. In addition, rectal temperature and the plasma concentrations of norepinephrine, corticosterone, and renin were also not changed by ghrelin. These findings demonstrate that ghrelin stimulates the gastric efferent vagus nerve in an organ-specific manner without affecting the gastric afferent vagus nerve and that ghrelin does not acutely affect the efferent basal activity of the sympathetic nerve in rats. PMID:24366191

Habara, Hiromi; Hayashi, Yujiro; Inomata, Norio; Niijima, Akira; Kangawa, Kenji

2014-01-01

109

Structure-activity relationship for the reactivators of acetylcholinesterase inhibited by nerve agent VX.  

Science.gov (United States)

Nerve agents such as sarin, VX and tabun are organophosphorus compounds able to inhibit an enzyme acetylcholinesterase (AChE). AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. None from the known AChE reactivators is able to reactivate AChE inhibited by all kinds of nerve agents. In this work, reactivation potency of seventeen structurally different AChE reactivators was tested in vitro and subsequently, relationship between their chemical structure and biological activity was outlined. VX was chosen as appropriate member of the nerve agent family. PMID:22779796

Kuca, Kamil; Musilek, Kamil; Jun, Daniel; Karasova, Jana; Soukup, Ondrej; Pejchal, Jaroslav; Hrabinova, Martina

2013-08-01

110

Brain-Derived Neurotrophic Factor from Bone Marrow-Derived Cells Promotes Post-Injury Repair of Peripheral Nerve  

OpenAIRE

Brain-derived neurotrophic factor (BDNF) stimulates peripheral nerve regeneration. However, the origin of BNDF and its precise effect on nerve repair have not been clarified. In this study, we examined the role of BDNF from bone marrow-derived cells (BMDCs) in post-injury nerve repair. Control and heterozygote BDNF knockout mice (BDNF+/?) received a left sciatic nerve crush using a cerebral blood clip. Especially, for the evaluation of BDNF from BMDCs, studies with bone marrow transplantati...

Takemura, Yoshinori; Imai, Shinji; Kojima, Hideto; Katagi, Miwako; Yamakawa, Isamu; Kasahara, Toshiyuki; Urabe, Hiroshi; Terashima, Tomoya; Yasuda, Hitoshi; Chan, Lawrence; Kimura, Hiroshi; Matsusue, Yoshitaka

2012-01-01

111

Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve injury.  

Science.gov (United States)

Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from substances by three enzymes: cystathionine ?-synthase (CBS), cystathionine ?-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). In human tissues, these enzymes are involved in tissue-specific biochemical pathways for H2 S production. For example, CBS and cysteine aminotransferase/MST are present in the brain, but CSE is not. Thus, we examined the expression of H2 S production-related enzymes in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase, but not CBS, were present in normal peripheral nerves. In addition, injured sciatic nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration (WD); however, CSE was not up-regulated in peripheral axons. Using an ex vivo sciatic nerve explant culture, we found that the inhibition of H2 S production broadly prevented the process of nerve degeneration, including myelin fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann cell proliferation in vitro and in vivo. Thus, these results indicate that H2 S signaling is essential for Schwann cell responses to peripheral nerve injury. Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from cystathionine ?-synthase (CBS), cystathionine ?-lyase (CSE), and 3-mercaptopyruvate sulfur transferase (MST). Here, we found that CSE and MST/CAT were present in normal peripheral nerves. Injured static nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration, but CSE was not up-regulated in peripheral axons. PMID:25123509

Park, Byung Sun; Kim, Hyun-Wook; Rhyu, Im Joo; Park, Chan; Yeo, Seung Geun; Huh, Youngbuhm; Jeong, Na Young; Jung, Junyang

2015-01-01

112

Quantitative structure-activity relationships of imidazolium oximes as nerve agent antidotes  

Energy Technology Data Exchange (ETDEWEB)

Organophosphorus-containing pesticides and chemical warfare agents are potent inhibitors of synaptic acetylcholinesterase, a key regulator of cholinergic neurotransmission. These nerve agents have for many years constituted a serious threat to military personnel. These threats stimulated considerable efforts to develop effective medical countermeasures. Several potential drugs have been found recently which are capable of protecting animals from lethal levels of nerve agents. A recent U. S. Army Medical Research and Development Command drug development project synthesized a large number of imidazolium oximes. These compounds were found to possess strong antidotal activity against one of the most lethal nerve agents, soman. The Army's approach, like most conventional drug discovery approaches, depended primarily on the trial and error method. This research was carried out to determine if these potential nerve agent antidotes could have been discovered through the use of Quantitative Structure Activity-Relationships (QSAR) technique.

Musallam, H.A.; Foye, W.O.; Hansch, C.; Harris, R.N.; Engle, R.R.

1993-05-13

113

Intramuscular injection of bone marrow mesenchymal stem cells with small gap neurorrhaphy for peripheral nerve repair.  

Science.gov (United States)

We had previously reported that small gap neurorrhaphy by scissoring and sleeve-jointing epineurium could enhance the rate and quality of peripheral nerve regeneration. To date, local implantation and systemic delivery of bone marrow mesenchymal stem cells (BMSCs) have been routinely used in nerve tissue engineering, but they each have some intrinsic limitations. We hypothesised that targeted muscular administration of BMSCs capable of reaching the damaged nerve would be advisable. Here, we investigated the therapeutic efficacy of transplantation of BMSCs through targeted muscular injection with small gap neurorrhaphy by scissoring and sleeve-jointing epineurium on repairing peripheral nerve injury in a rat model. One week after a rat model of peripheral nerve injury was established by small gap neurorrhaphy, thirty-six Sprague-Dawley rats were randomly divided into three groups (n=12): the intramuscular injection of BMSCs group (IM), the intravenous injection of BMSCs group (IV) and the intramuscular injection of phosphate-buffered solution group (PBS). The process of the nerve regeneration was assayed functionally and morphologically. The results indicated that compared to the IV-treated and PBS-treated groups, the targeted muscular injection therapy resulted in much more beneficial effects, as evidenced by increases in the sciatic function index, nerve conduction velocity, myelin sheath thickness and restoration rate of gastrocnemius muscle wet weight. In conclusion, the combination therapy of small gap neurorrhaphy and BMSC transplantation through targeted muscular injection can significantly promote the regeneration of peripheral nerve and improve the nerve's functional recovery, which may help establish a reliable approach for repairing peripheral nerve injury. PMID:25434870

Wang, Peiji; Zhang, Yong; Zhao, Jiaju; Jiang, Bo

2015-01-12

114

Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Although several anti-angiogenic therapies have been approved in the treatment of cancer, the survival benefits of such therapies are relatively modest. Discovering new molecules and/or better understating signaling pathways of angiogenesis is therefore essential for therapeutic improvements. The objective of the present study was to determine the involvement of nerve growth factor (NGF in breast cancer angiogenesis and the underlying molecular mechanisms. Results We showed that both recombinant NGF and NGF produced by breast cancer cells stimulated angiogenesis in Matrigel plugs in immunodeficient mice. NGF strongly increased invasion, cord formation and the monolayer permeability of endothelial cells. Moreover, NGF-stimulated invasion was under the control of its tyrosine kinase receptor (TrkA and downstream signaling pathways such as PI3K and ERK, leading to the activation of matrix metalloprotease 2 and nitric oxide synthase. Interestingly, NGF increased the secretion of VEGF in both endothelial and breast cancer cells. Inhibition of VEGF, with a neutralizing antibody, reduced about half of NGF-induced endothelial cell invasion and angiogenesis in vivo. Conclusions Our findings provided direct evidence that NGF could be an important stimulator for breast cancer angiogenesis. Thus, NGF, as well as the activated signaling pathways, should be regarded as potential new targets for anti-angiogenic therapy against breast cancer.

Adriaenssens Eric

2010-06-01

115

Third cranial nerve palsies in childhood. A case report of sellar germ cell tumor  

OpenAIRE

PURPOSE: Third cranial nerve palsies are unfrequent in childhood and adolescence and are most often congenital. The association of sellar germ cell tumor and ophthalmoplegia is considered as being very rare at this age. CASE REPORT: A 11-year-old young girl was examined in emergency with a third left cranial nerve partial palsy associated with one- year duration history of hypopituitarism with insipid diabetes and growth retardation. Cerebral IRM revealed a tumor of the pituitary gland. In hi...

Kalenga, Mbu; Collignon, Nathalie; Andris, Ce?cile; Deprez, Manuel; Otto, Bernard

2011-01-01

116

Mast cells and the cyclooxygenase pathway mediate colonic afferent nerve sensitization in a murine colitis model  

OpenAIRE

INTRODUCTION: Intestinal inflammation alters colonic afferent nerve sensitivity which may contribute to patients' perception of abdominal discomfort. We aimed to explore whether mast cells and the cyclooxygenase pathway are involved in altered afferent nerve sensitivity during colitis. METHODS: C57Bl6 mice received 3% dextran-sulfate sodium (DSS) in drinking water for 7 days to induce colitis. Control animals received regular water. On day 8 inflammation was assessed in the proximal colon ...

Xue, B.; Mu?ller, M. H.; Li, J.; Pesch, T.; Kasparek, M. S.; Sibaev, A.; Hausmann, M.; Rogler, G.; Kreis, M. E.

2013-01-01

117

Activation of the Bcl-2 promoter by nerve growth factor is mediated by the p42/p44 MAPK cascade  

OpenAIRE

The Bcl-2 protein has an anti-apoptotic effect in neuronal and other cell types. We show for the first time that the Bcl-2 promoter is activated by the neuronal survival factor nerve growth factor (NGF) and that this effect is dependent on a region of the promoter from -1472 to -1414. This activation requires the Rap-1 G protein and the MEK-1 and p42/p44 MAPK enzymes but is independent of other NGF-activated signalling pathways involving protein kinase A or protein kinase C.

Liu, Y. Z.; Boxer, L. M.; Latchman, D. S.

1999-01-01

118

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

International Nuclear Information System (INIS)

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

119

Differential Effects of Electrical Stimulation of Sciatic Nerve on Metabolic Activity in Spinal Cord and Dorsal Root Ganglion in the Rat  

Science.gov (United States)

Electrical stimulation of the proximal stump of the transected sciatic nerve produces a frequency-dependent activation of glucose utilization, measured with the autoradiographic deoxy[14C]glucose method, in the dorsal horn of the spinal cord but produces no change in glucose utilization in the dorsal root ganglion cells. These results suggest that axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased functional activity of this pathway.

Kadekaro, Massako; Crane, Alison M.; Sokoloff, Louis

1985-09-01

120

Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat.  

OpenAIRE

Electrical stimulation of the proximal stump of the transected sciatic nerve produces a frequency-dependent activation of glucose utilization, measured with the autoradiographic deoxy [14C]glucose method, in the dorsal horn of the spinal cord but produces no change in glucose utilization in the dorsal root ganglion cells. These results suggest that axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased functional activity of this pathway.

Kadekaro, M.; Crane, A. M.; Sokoloff, L.

1985-01-01

121

Nerve growth factor-induced alteration in the response of PC12 pheochromocytoma cells to epidermal growth factor  

OpenAIRE

PC12 cells, which differentiate morphologically and biochemically into sympathetic neruonlike cells in response to nerve growth fact, also respond to epidermal growth factor. The response to epidermal growth factor is similar in certain respects to the response to nerve growth fact. Both peptides produce rapid increases in cellular adhesion and 2-deoxyglucose uptake and both induce ornithine decarboxylase. But nerve growth factor causes a decreased cell proliferation and a marked hypertrophy ...

Huff, K.; End, D.; Guroff, G.

1981-01-01

122

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

123

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion  

Science.gov (United States)

Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell (SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration. PMID:25621102

Fairbairn, Neil G; Meppelink, Amanda M; Ng-Glazier, Joanna; Randolph, Mark A; Winograd, Jonathan M

2015-01-01

124

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion  

Science.gov (United States)

Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell (SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration.

Fairbairn, Neil G; Meppelink, Amanda M; Ng-Glazier, Joanna; Randolph, Mark A; Winograd, Jonathan M

2015-01-01

125

Mirror-image pain is mediated by nerve growth factor produced from tumor necrosis factor alpha-activated satellite glia after peripheral nerve injury.  

Science.gov (United States)

Mirror-image pain is characterized by mechanical hypersensitivity on the uninjured mirror-image side. Recent reports favor central mechanisms, but whether peripheral mechanisms are involved remains unclear. We used unilateral spinal nerve ligation (SNL) to induce mirror-image pain in rats. On the mirror-image (contralateral) side, we found that satellite glia in the dorsal root ganglion (DRG) were activated, whereas macrophages/Schwann cells in the DRG and astrocytes/oligodendrocytes/microglia in the dorsal spinal cord were not. Subsequently, an increase in nerve growth factor (NGF) was detected in the contralateral DRG, and NGF immunoreactivity was concentrated in activated satellite glia. These phenomena were abolished if fluorocitrate (a glial inhibitor) was intrathecally injected before SNL. Electrophysiological recordings in cultured small DRG neurons showed that exogenous NGF enhanced nociceptor excitability. Intrathecal injection of NGF into naive rats induced long-lasting mechanical hypersensitivity, similar to SNL-evoked mirror-image pain. Anti-NGF effectively relieved SNL-evoked mirror-image pain. In the contralateral DRG, the SNL-evoked tumor necrosis factor alpha (TNF-?) increase, which started later than in the ipsilateral DRG and cerebrospinal fluid, occurred earlier than satellite glial activation and the NGF increase. Intrathecal injection of TNF-? into naive rats not only activated satellite glia to produce extra NGF in the DRG but also evoked mechanical hypersensitivity, which could be attenuated by anti-NGF injection. These results suggest that after SNL, satellite glia in the contralateral DRG are activated by TNF-? that diffuses from the injured side via cerebrospinal fluid, which then activates satellite glia to produce extra NGF to enhance nociceptor excitability, which induces mirror-image pain. PMID:24447514

Cheng, Chau-Fu; Cheng, Jen-Kun; Chen, Chih-Yang; Lien, Cheng-Chang; Chu, Dachen; Wang, Szu-Yi; Tsaur, Meei-Ling

2014-05-01

126

Computation of induced electric field for the sacral nerve activation  

International Nuclear Information System (INIS)

The induced electric field/current in the sacral nerve by stimulation devices for the treatment of bladder overactivity is investigated. Implanted and transcutaneous electrode configurations are considered. The electric field induced in the sacral nerve by the implanted electrode is largely affected by its surrounding tissues, which is attributable to the variation in the input impedance of the electrode. In contrast, the electric field induced by the transcutaneous electrode is affected by the tissue conductivity and anatomical composition of the body. In addition, the electric field induced in the subcutaneous fat in close proximity of the electrode is comparable with the estimated threshold electric field for pain. These computational findings explain the clinically observed weakness and side effect of each configuration. For the transcutaneous stimulator, we suggest that the electrode contact area be increased to reduce the induced electric field in the subcutaneous fat. (paper)

127

Differential activation of nerve fibers with magnetic stimulation in humans  

Directory of Open Access Journals (Sweden)

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.

Olree Kenneth S

2006-07-01

128

Effect of allotransplants containing dissociated cells of rat embryonic spinal cord on nerve fiber regeneration in a recipient.  

Science.gov (United States)

Regeneration of nerve fibers in rat sciatic nerve was quantitatively assessed after injury (ligation) and injection of dissociated cells derived from embryonic spinal cord. A suspension of dissociated spinal cord cells from rat embryos was transplanted under the perineurium of a nerve trunk. After transplantation, bromodeoxyuridine-labeled precursor cells survived and retained the label for more than 2 months; some of these cells differentiated into NeuNpositive neurons. Analysis of semithin sections of the distal nerve segment from the recipient taken at a distance of 0.5 cm from the site of injury showed that transplantation of dissociated cells of embryonic spinal cord led to an increase in the number of myelinated nerve fibers in the recipient nerve. PMID:25403413

Petrova, E S; Isaeva, E N; Korzhevskii, D E

2014-11-01

129

Satellite glial cell proliferation in the trigeminal ganglia after chronic constriction injury of the infraorbital nerve.  

Science.gov (United States)

We have examined satellite glial cell (SGC) proliferation in trigeminal ganglia following chronic constriction injury of the infraorbital nerve. Using BrdU labeling combined with immunohistochemistry for SGC specific proteins we positively confirmed proliferating cells to be SGCs. Proliferation peaks at approximately 4 days after injury and dividing SGCs are preferentially located around neurons that are immunopositive for ATF-3, a marker of nerve injury. After nerve injury there is an increase GFAP expression in SGCs associated with both ATF-3 immunopositive and immunonegative neurons throughout the ganglia. SGCs also express the non-glial proteins, CD45 and CD163, which label resident macrophages and circulating leukocytes, respectively. In addition to SGCs, we found some Schwann cells, endothelial cells, resident macrophages, and circulating leukocytes were BrdU immunopositive. PMID:24123473

Donegan, Macayla; Kernisant, Melanie; Cua, Criselda; Jasmin, Luc; Ohara, Peter T

2013-12-01

130

Regulating schwann cells growth by chitosan micropatterning for peripheral nerve regeneration in vitro.  

Science.gov (United States)

To address the effect of chitosan micropatterning on nerve regeneration, two sizes of parallel microstripes of chitosan are fabricated on the surface of coverslips using a micromodeling method. The morphology of the prepared polydimethylsiloxane stamps and chitosan micropatterning is observed by scanning electron microscopy and the wettability of the prepared micropatterning is evaluated using water contact-angle measurements. Schwann cell (SC) culture is used to evaluate the effect of chitosan micropatterning on cell behavior. The results show that the stripe-like chitosan micropatterning can be successfully fabricated on coverslip surfaces. SCs on 30/30??m chitosan micropatterning shows the most obvious cell orientation. Moreover, the secretion of nerve growth factor by SCs indicate that the chitosan micropatterning has no negative influence on the normal physiological function of the cells. Thus, the study suggests that chitosan micropatterning can induce and regulate the growth of SCs well, which may have potential application in peripheral nerve regeneration. PMID:24757089

Li, Guicai; Zhao, Xueying; Zhang, Luzhong; Wang, Caiping; Shi, Yunwei; Yang, Yumin

2014-08-01

131

Current progress in use of adipose derived stem cells in peripheral nerve regeneration  

Science.gov (United States)

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair.

Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

2015-01-01

132

Nerve Injury Increases Brain-Derived Neurotrophic Factor Levels to Suppress BK Channel Activity in Primary Sensory Neurons  

OpenAIRE

Abnormal hyperexcitability of primary sensory neurons contributes to neuropathic pain development after nerve injury. Nerve injury profoundly reduces the expression of big conductance Ca2+-activated K+ (BK) channels in the dorsal root ganglion (DRG). However, little is known about how nerve injury affects BK channel activity in DRG neurons. In this study, we determined the changes in BK channel activity in different sizes of DRG neurons in a rat model of neuropathic pain and the contribution ...

Cao, Xue-hong; Chen, Shao-rui; Li, Li; Pan, Hui-lin

2012-01-01

133

Ultrastructure of the ganglion cells of the terminal nerve in the dwarf gourami (Colisa lalia).  

Science.gov (United States)

In our previous light microscopic studies (Oka et al., Brain Res. 367: 341-345, '86; Oka and Ichikawa, J. Comp. Neurol. 300: 511-522, '90), we reported that there are at least two types of terminal nerve (TN) cells based on cell size and immunoreactivity: type I cells had large cell bodies, while type II cells had smaller cell bodies. Type I TN cells were immunoreactive to gonadotropin-releasing hormone (GnRH) and may be the major source of GnRH-immunoreactive fibers that are widely distributed throughout the brain. Type II TN cells, on the other hand, were not immunoreactive to GnRH. In the present paper, we examined the cytology and synaptology of these two types of TN cells with electron microscopy. Type I TN cell bodies were found to have morphological characteristics similar to those of other peptide-synthesizing neurons and are likely to be actively synthesizing GnRH. The frequent occurrence of coated vesicles close to the plasma membrane of the cell body was suggestive of membrane retrieval following exocytosis of the vesicular contents from the cell surface. Neighboring TN cells were either in direct juxtaposition with one another or made specialized "glomeruloid" cell-to-cell contacts; these specializations may be relevant for nonsynaptic intercellular communications among the TN cells. Within these glomeruloid complexes, the somatic processes of TN cells received inputs from two types of synaptic terminals: one containing only spherical synaptic vesicles and another containing a small number of dense-cored vesicles in addition to the spherical synaptic vesicles. Axosomatic synapses were rare on type I TN cell bodies. In contrast, type II TN cell bodies had morphological characteristics similar to those of neurons in other brain regions. These receive axosomatic inputs from synaptic terminals containing only spherical synaptic vesicles and those with a small number of dense-cored vesicles in addition to the spherical synaptic vesicles. Thus, each type of TN cell has unique fine structural characteristics which may correlate to their different functional roles. PMID:1901871

Oka, Y; Ichikawa, M

1991-02-01

134

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

Directory of Open Access Journals (Sweden)

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.

Evan B. Stubbs

2013-02-01

135

Mast cell and lymphoreticular infiltrates in neurofibromas. Comparison with nerve sheath tumors.  

Science.gov (United States)

Cellular heterogeneity produced by non-Schwannian elements may distinguish neurofibromas from other Schwann cell neoplasma and contribute to a different tumor biology. The present study compared cell counts of mast cells, T and B lymphocytes, and macrophages in 32 neurofibromas with those in 27 schwannomas, 9 malignant nerve sheath tumors, and 17 traumatic neuromas. Immunohistochemical and histochemical analyses were performed on formalin-fixed, paraffin-embedded tissues using two monoclonal antibodies against B-lymphocyte epitopes (LN-1 and LN-2), one monoclonal antibody against T-lymphocyte epitopes (UCHL-1), one polyclonal antibody recognizing alpha 1-antichymotrypsin (ACT), a macrophage/histiocytemarker, and toluidine blue O stains. Neurofibromas contained relatively high concentrations of mast cells significantly greater than the concentrations in other neoplastic or reactive nerve sheath tumors. Most neurofibromas also displayed moderate concentrations of LN-2 immunoreactive cells, similar to the concentrations in traumatic neuromas and not statistically different from cell counts in other tumor types. Limited, variable LN-1 and UCHL-1 immunoreactive infiltrates were detected in neurofibromas and some peripheral schwannomas. Rare or moderate ACT immunoreactivity was detected in the majority of neurofibromas, in contrast with the absence, or rare appearance, of ACT immunostaining in cranial and peripheral nerve schwannomas and moderate numbers of immunoreactive cells in many malignant nerve sheath tumors. Mast cells are an important cellular marker of neurofibromas and may participate in the pathogenesis of these neoplasms. PMID:2479359

Johnson, M D; Kamso-Pratt, J; Federspiel, C F; Whetsell, W O

1989-11-01

136

Nitric oxide modulates bladder afferent nerve activity in the in vitro urinary bladder–pelvic nerve preparation from rats with cyclophosphamide induced cystitis  

OpenAIRE

Effects of a nitric oxide (NO) donor (SNAP), NO substrate (l-arginine), and NO synthase inhibitor (l-NAME) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder–pelvic nerve preparation from untreated or cyclophosphamide (CYP) treated rats. Distension of the bladder induced phasic bladder contractions (PBC) that were accompanied by multiunit afferent firing. Intravesical administration of SNAP (2 mM) which did not change the amplitude of PBC significantly decreased pe...

Yu, Yongbei; Groat, William C.

2012-01-01

137

Modulation by somatostatin of nerve-mediated activation of glycogenolysis in the perfused rat liver.  

Science.gov (United States)

Perivascular nerve stimulation of rat livers perfused in situ with erythrocyte-free Krebs-Henseleit buffer at constant pressure in a non-recirculating system resulted in an increase of glucose and lactate production and in a decrease of portal flow. Infusion of somatostatin in different concentrations (2 x 10(-7), 10(-8), 10(-9) mol.l-1) reduced the nerve-mediated activation of glucose release maximally to 66%. There was only a slight effect on the lactate output, the nerve-mediated reduction of portal flow was unaltered. In controls, somatostatin alone had no effect on the metabolic and hemodynamic parameters. In order to differentiate between a presynaptic and postsynaptic mechanism, the noradrenaline overflow was calculated. The unaltered release of the neurotransmitter in the presence or absence of somatostatin excluded a presynaptic mechanism. To mimic the nerve effects on the carbohydrate metabolism and on the hemodynamics, noradrenaline (2 x 10(-7) mol.l-1) was infused instead of the nerve stimulation over a period of 5 min. Somatostatin did not change the endocrine effects of the catecholamine under these conditions. The nerve-dependent effect of somatostatin suggests that other neurotransmitters (e.g. VIP) or mediators (e.g. prostanoids) may be influenced by somatostatin. PMID:2568947

Beckh, K; Ehlenz, K; Arnold, R

1989-07-01

138

Autocrine/paracrine modulation of baroreceptor activity after antidromic stimulation of aortic depressor nerve in vivo.  

Science.gov (United States)

Activation of the sensory nerve endings of non-myelinated C-fiber afferents evokes release of autocrine/paracrine factors that cause localized vasodilation, neurogenic inflammation, and modulation of sensory nerve activity. The aims of this study were to determine the effect of antidromic electrical stimulation on afferent baroreceptor activity in vivo, and investigate the role of endogenous prostanoids and hydrogen peroxide (H2O2) in mediating changes in nerve activity. Baroreceptor activity was recorded from the left aortic depressor nerve (ADN) in anesthetized rats before and after stimulating the ADN for brief (5–20 s) periods. The rostral end of the ADN was crushed or sectioned beforehand to prevent reflex changes in blood pressure. Antidromic stimulation of ADN using parameters that activate both myelinated A-fibers and non-myelinated C-fibers caused pronounced and long-lasting (> 1 min) inhibition of baroreceptor activity (n = 9, P ADN and suggest that endogenous prostanoids and H2O2 oppose and mediate the inhibition, respectively. These mechanisms may contribute to rapid baroreceptor resetting during acute hypertension and be engaged during chronic baroreceptor activation therapy in patients with hypertension. PMID:24567955

Santana-Filho, Valter J; Davis, Greg J; Castania, Jaci A; Ma, Xiuying; Salgado, Helio C; Abboud, Francois M; Fazan, Rubens; Chapleau, Mark W

2014-02-01

139

Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus  

Directory of Open Access Journals (Sweden)

Full Text Available Feedforward inhibition represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs, principal neurons of the dorsal cochlear nucleus (DCN that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and feed-forward inhibition in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven feed-forward inhibition (FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of feed-forward inhibition had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

Stephan Brenowitz

2014-07-01

140

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

141

Gulf War illnesses are autoimmune illnesses caused by increased activity of the p38/MAPK pathway in CD4+ immune system cells, which was caused by nerve agent prophylaxis and adrenergic load.  

Science.gov (United States)

Sodium chloride intake might increase the risk for the development of autoimmune diseases by increasing the activity of the p38/MAPK pathway in CD4+ cells thereby producing pathogenic TH17 cells which are inflammatory. Two factors (muscarinic and beta adrenergic stimulation), already shown to potentiate each other's toxic effects in whole mice, and have combined amplified sub lethal effects on mouse T cells, can have the same effect on CD4+ signaling pathways as sodium chloride. Sick 1991 Gulf War veterans express elevated Th17 cytokine activity, and therefore may have autoimmune illnesses caused directly by the above mentioned exposures. PMID:24095261

Moss, J I

2013-12-01

142

Calcineurin activation causes retinal ganglion cell degeneration  

OpenAIRE

Purpose: We previously reported that calcineurin, a Ca2+/calmodulin-dependent serine/threonine phosphatase, is activated and proposed that it participates in retinal ganglion cell (RGC) apoptosis in two rodent ocular hypertension models. In this study, we tested whether calcineurin activation by itself, even in the absence of ocular hypertension, is sufficient to cause RGC degeneration. Methods: We compared RGC and optic nerve morphology after adeno-associated virus serotype 2 (AAV2)–mediat...

Qu, Juan; Matsouaka, Roland Albert; Betensky, Rebecca Aubrey; Hyman, Bradley Theodore; Grosskreutz, Cynthia Lee

2012-01-01

143

A comparative study of axon-surrounding cells in the two nasal nerve tracts from mouse olfactory epithelium and vomeronasal organ.  

Science.gov (United States)

The olfactory and vomeronasal systems are the two nasal chemical detectors in mammals. While glial cells in the olfactory nerve tracts have been well-investigated, little is known about cells in the vomeronasal nerve tracts. In the present study, we compared the expression patterns of marker proteins in the cells comprising the two nasal nerve tracts in mice. Neural crest-derived cells surrounded the olfactory nerve axons in the lamina propria of the olfactory epithelium. These cells expressed glial fibrillary acidic protein (GFAP) and p75 glycoprotein, which are markers of olfactory ensheathing cells. Neural crest-derived cells also surrounded the vomeronasal nerve axons in the lamina propria of the vomeronasal epithelium. These nerve axon-surrounding cells, however, did not express GFAP or p75. Rather, the vomeronasal nerve axons expressed GFAP and p75. These results suggest that axon-surrounding cells functionally differ between the olfactory and vomeronasal nerve tracts. PMID:23410787

Nakajima, Mitsunari; Tsuruta, Momoko; Mori, Hisamichi; Nishikawa, Chisa; Okuyama, Satoshi; Furukawa, Yoshiko

2013-03-29

144

A synthetic oxygen carrier-olfactory ensheathing cell composition system for the promotion of sciatic nerve regeneration.  

Science.gov (United States)

The treatment of lengthy peripheral nerve defects is challenging in the field of the regenerative medicine. Thus far, many nerve scaffolds with seeded cells have been developed, which hold great potential to replace nerve autograft in bridging lengthy nerve defects by providing guiding and bioactive cues. However, low oxygen status has been found within nerve scaffolds after their implantation in vivo, which has been shown to result in death or loss of function of supportive cells, and significantly limit nerve regeneration and functional recovery after nerve injury. In the present study, perfluorotributylamine (PFTBA) was introduced into a collagen-chitosan conduit within which olfactory ensheathing cells (OECs) were seeded to increase oxygen supply to OECs, as well as regenerating axons. The "PFTBA-OECs" enriched scaffolds were then used to bridge a 15-mm-long sciatic nerve defect in rats. Both nerve regeneration and functional recovery were examined at pre-defined time points after surgery. We found that the number of GFP-labeled OECs was significantly higher in the "PFTBA-OECs" scaffold than that in the single OECs scaffold. In addition, PFTBA was found to enhance the beneficial effect of OECs-enriched scaffold on axonal regeneration and functional recovery. All these findings indicate that the "PFTBA-OECs" enriched scaffolds are capable of promoting nerve regeneration and functional recovery, which might be attributable, at least in part, to their beneficial effect on the survival of OECs after their implantation in vivo. PMID:24246645

Zhu, Shu; Ge, Jun; Wang, Yuqing; Qi, Fengyu; Ma, Teng; Wang, Meng; Yang, Yafeng; Liu, Zhongyang; Huang, Jinghui; Luo, Zhuojing

2014-02-01

145

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

Directory of Open Access Journals (Sweden)

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.

Al-Jashamy Karim

2011-01-01

146

The pan erbB inhibitor PD168393 enhances lysosomal dysfunction-induced apoptotic death in malignant peripheral nerve sheath tumor cells  

OpenAIRE

Malignant peripheral nerve sheath tumors (MPNSTs) are rapidly progressive Schwann cell neoplasms. The erbB family of membrane tyrosine kinases has been implicated in MPNST mitogenesis and invasion and, thus, is a potential therapeutic target. However, tyrosine kinase inhibitors (TKIs) used alone have limited tumoricidal activity. Manipulating the autophagy lysosomal pathway in cells treated with cytostatic agents can promote apoptotic cell death in some cases. The goal of this study was to es...

Kohli, Latika; Kaza, Niroop; Lavalley, Nicholas J.; Turner, Kathryn L.; Byer, Stephanie; Carroll, Steven L.; Roth, Kevin A.

2012-01-01

147

Axon-Schwann cell interaction in degenerating and regenerating peripheral nerve  

International Nuclear Information System (INIS)

Severance of a peripheral nerve stimulates a characteristic sequence of events in the distal stump, including the dissolution of axons and myelin and the proliferation of Schwann cells within their basal lamina. The first part of this thesis employs the cat tibial nerve to examine the relationship between the spatio-temporal pattern of Schwann cell mitosis, loss of the structural and functional properties of axolemma, synthesis of P0, the major myelin glycoprotein, and the clearance of morphological myelin. Induction of S phase was measured by determining the uptake of 3H thymidine into trichloroacetic acid (TCA) precipitates following a 3 hour in vitro incubation in Krebs-Ringers buffer containing 3H thymidine. Nerve transection stimulated a monophasic increase in 3H thymidine uptake that peaked at 4 days post-transection throughout an 80 mm length of distal stump. Light microscope autoradiography revealed prominent incorporation into Schwann cells of myelinated fibers. Nerve transection also produced dramatic changes in the intrafascicular binding of 3H STX which binds to voltage-sensitive sodium channels STX binding fell precipitously to 20% of normal at 4 days post-transection, concurrent with the peak of 3H thymidine uptake. In conclusion, these studies suggest: (a) Schwann cells divide more or less contemporaneously throughout the distal stump; (b) changes in axons rather than myelin are likely to stimulate the Schwann cell to divide; (c) mitosis regulates other events during Wallerian degeneration, including myelin degeneration and the clearance of sodium channels from nodal axolemma

148

Promoting Nerve Cell Functions on Hydrogels Grafted with Poly(L-lysine)  

OpenAIRE

We present a novel photo-polymerizable poly(L-lysine) (PLL) and use it to modify polyethylene glycol diacrylate (PEGDA) hydrogels for creating a better, permissive nerve cell niche. Compared with their neutral counterparts, these PLL-grafted hydrogels greatly enhance pheochromocytoma (PC12) cell survival in encapsulation, proliferation, and neurite growth, and also promote neural progenitor cell proliferation and differentiation capacity, represented by percentages of both differentiated neur...

Cai, Lei; Lu, Jie; Sheen, Volney; Wang, Shanfeng

2012-01-01

149

Phosphatidylcholine-specific phospholipase C regulates glutamate-induced nerve cell death  

OpenAIRE

Phosphatidylcholine-specific phospholipase C (PC-PLC) is a necessary intermediate in transducing apoptotic signals for tumor necrosis factor and Fas/Apo-1 ligands in nonneuronal cells. The data presented here show that PC-PLC also is required in oxidative glutamate-induced programmed cell death of both immature cortical neurons and a hippocampal nerve cell line, HT22. In oxidative glutamate toxicity, which is distinct from excitotoxicity, glutamate interferes with cystine uptake by blocking t...

Li, Yonghong; Maher, Pamela; Schubert, David

1998-01-01

150

Olfactory ensheathing cells: the primary innate immunocytes in the olfactory pathway to engulf apoptotic olfactory nerve debris.  

Science.gov (United States)

The olfactory system is an unusual tissue in which olfactory receptor neurons (ORNs) are continuously replaced throughout the life of mammals. Clearance of the apoptotic ORNs corpses is a fundamental process serving important functions in the regulation of olfactory nerve turnover and regeneration. However, little is known about the underlying mechanisms. Olfactory ensheathing cells (OECs) are a unique type of glial cells that wrap olfactory axons and support their continual regeneration from the olfactory epithelium to the bulb. In the present study, OECs were identified to exist in two different states, resting and reactive, in which resting OECs could be activated by LPS stimulation and functioned as phagocytes for cleaning apoptotic ORNs corpses. Confocal analysis revealed that dead ORNs debris were engulfed by OECs and co-localized with lysosome associated membrane protein 1. Moreover, phosphatidylserine (PS) receptor was identified to express on OECs, which allowed OECs to recognize apoptotic ORNs by binding to PS. Importantly, engulfment of olfactory nerve debris by OECs was found in olfactory mucosa under normal turnover and was significantly increased in the animal model of olfactory bulbectomy, while little phagocytosis by Iba-1-positive microglia/macrophages was observed. Together, these results implicate OEC as a primary innate immunocyte in the olfactory pathway, and suggest a cellular and molecular mechanism by which ORNs corpses are removed during olfactory nerve turnover and regeneration. PMID:23339073

Su, Zhida; Chen, Jingjing; Qiu, Yang; Yuan, Yimin; Zhu, Feng; Zhu, Yanling; Liu, Xiujie; Pu, Yingyan; He, Cheng

2013-04-01

151

Up-regulation of HDAC4 is associated with Schwann cell proliferation after sciatic nerve crush.  

Science.gov (United States)

Histone deacetylase 4 (HDAC4), a member of the class IIa HDACs subfamily, has emerged as a critical regulator of cell growth, differentiation, and migration in various cell types. It was reported that HDAC4 stimulated colon cell proliferation via repression of p21. Also, HDAC4 contributes to platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells. Furthermore, HDAC4 may play an important role in the regulation of neuronal differentiation and survival. However, the role of HDAC4 in the process of peripheral nervous system regeneration after injury remains virtually unknown. Herein, we investigated the spatiotemporal expression of HDAC4 in a rat sciatic nerve crush model. We found that sciatic nerve crush induced up-regulated expression of HDAC4 in Schwann cells. Moreover, the expression of the proliferation marker Ki-67 exhibited a similar tendency with that of HDAC4. In cell cultures, we observed increased expression of HDAC4 during the process of TNF-?-induced Schwann cell proliferation, whereas the protein level of p21 was down-regulated. Interference of HDAC4 led to enhanced expression of p21 and impaired proliferation of Schwan cells. Taken together, our findings implicated that HDAC4 was up-regulated in the sciatic nerve after crush, which was associated with proliferation of Schwann cells. PMID:25103231

Liu, Yonghua; Liu, Yang; Nie, Xiaoke; Cao, Jianhua; Zhu, Xiaojian; Zhang, Weidong; Liu, Zhongbing; Mao, Xingxing; Yan, Shixian; Ni, Yingjie; Wang, Youhua

2014-11-01

152

Conserved Dopamine Neurotrophic Factor-Transduced Mesenchymal Stem Cells Promote Axon Regeneration and Functional Recovery of Injured Sciatic Nerve  

OpenAIRE

Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. Scanning...

Liu, Yi; Nie, Lin; Zhao, Hua; Zhang, Wen; Zhang, Yuan-qiang; Wang, Shuai-shuai; Cheng, Lei

2014-01-01

153

The rate of diffusion of Ca2+ and Ba2+ in a nerve cell body.  

OpenAIRE

A spectrophotometric method was developed to directly measure the diffusion rate of Ca2+ and some other ions in nerve cell bodies, using pulsed ionophoretic injections and an optical microprobe to record locally absorbance changes of the dye arsenazo III. We report here that Ca2+ and Ba2+ diffuse at approximately the same rate in nerve soma cytoplasm, having effective diffusion coefficients in the range of 7-12 X 10(-7) cm2/s, while identical measurements conducted in an electrolytic solution...

Nasi, E.; Tillotson, D.

1985-01-01

154

Malignant trigeminal nerve sheath tumor and anaplastic astrocytoma collision tumor with high proliferative activity and tumor suppressor p53 expression.  

Science.gov (United States)

Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53) gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST) and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa. PMID:25386378

Kurdi, Maher; Al-Ardati, Hosam; Baeesa, Saleh S

2014-01-01

155

Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model.  

Science.gov (United States)

Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury. PMID:25377914

Deng, Kangli; Lin, Dan Li; Hanzlicek, Brett; Balog, Brian; Penn, Marc S; Kiedrowski, Matthew J; Hu, Zhiquan; Ye, Zhangqun; Zhu, Hui; Damaser, Margot S

2015-01-15

156

Muscle sympathetic nerve activity and hemodynamic alterations in middle-aged obese women  

Directory of Open Access Journals (Sweden)

Full Text Available To study the relationship between the sympathetic nerve activity and hemodynamic alterations in obesity, we simultaneously measured muscle sympathetic nerve activity (MSNA, blood pressure, and forearm blood flow (FBF in obese and lean individuals. Fifteen normotensive obese women (BMI = 32.5 ± 0.5 kg/m² and 11 age-matched normotensive lean women (BMI = 22.7 ± 1.0 kg/m² were studied. MSNA was evaluated directly from the peroneal nerve by microneurography, FBF was measured by venous occlusion plethysmography, and blood pressure was measured noninvasively by an autonomic blood pressure cuff. MSNA was significantly increased in obese women when compared with lean control women. Forearm vascular resistance and blood pressure were significantly higher in obese women than in lean women. FBF was significantly lower in obese women. BMI was directly and significantly correlated with MSNA, blood pressure, and forearm vascular resistance levels, but inversely and significantly correlated with FBF levels. Obesity increases sympathetic nerve activity and muscle vascular resistance, and reduces muscle blood flow. These alterations, taken together, may explain the higher blood pressure levels in obese women when compared with lean age-matched women.

Ribeiro M.M.

2001-01-01

157

Muscle sympathetic nerve activity and hemodynamic alterations in middle-aged obese women  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english To study the relationship between the sympathetic nerve activity and hemodynamic alterations in obesity, we simultaneously measured muscle sympathetic nerve activity (MSNA), blood pressure, and forearm blood flow (FBF) in obese and lean individuals. Fifteen normotensive obese women (BMI = 32.5 ± 0.5 [...] kg/m²) and 11 age-matched normotensive lean women (BMI = 22.7 ± 1.0 kg/m²) were studied. MSNA was evaluated directly from the peroneal nerve by microneurography, FBF was measured by venous occlusion plethysmography, and blood pressure was measured noninvasively by an autonomic blood pressure cuff. MSNA was significantly increased in obese women when compared with lean control women. Forearm vascular resistance and blood pressure were significantly higher in obese women than in lean women. FBF was significantly lower in obese women. BMI was directly and significantly correlated with MSNA, blood pressure, and forearm vascular resistance levels, but inversely and significantly correlated with FBF levels. Obesity increases sympathetic nerve activity and muscle vascular resistance, and reduces muscle blood flow. These alterations, taken together, may explain the higher blood pressure levels in obese women when compared with lean age-matched women.

M.M., Ribeiro; I.C., Trombetta; L.T., Batalha; M.U.P.B., Rondon; C.L.M., Forjaz; A.C.P., Barretto; S.M.F., Villares; C.E., Negrão.

2001-04-01

158

Changes in the Foxj1 expression of Schwann cells after sciatic nerve crush.  

Science.gov (United States)

Foxj1 is a member of the Forkhead box family of transcription factors expressed in multiple tissues during development and a major regulator of cilia development. It was reported that Foxj1 has a significant up-regulation after traumatic brain injury and plays an important role in central nervous system injury and repair. However, its expression and function in the peripheral nervous system lesion are not well understood. In this study, we investigated the spatiotemporal expression of Foxj1 in a rat sciatic nerve crush model. After never injury, we observed that Foxj1 had a significant up-regulation from 1 day, peaked at day 3 and then gradually decreased to the normal level at 4 weeks. At its peak expression, Foxj1 expressed mainly in Schwann cells (SCs) of the distal sciatic nerve segment from injury, but had few co-localizations in axons. Besides, the peak expression of Foxj1 was in parallel with proliferating cell nuclear antigen (PCNA), and numerous SCs expressing Foxj1 were PCNA positive. Collectively, we hypothesized that peripheral nerve crush-induced up-regulation of Foxj1 in the sciatic nerve was associated with Schwann cells proliferation. PMID:23515839

Cao, Jianhua; Cheng, Xinghai; Zhou, Zhengming; Sun, Huiqing; Zhou, Feng; Zhao, Jing; Liu, Yonghua; Cui, Gang

2013-08-01

159

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

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...

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

160

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)

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

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

2014-01-01

161

Advantage of recording single-unit muscle sympathetic nerve activity in heart failure  

Directory of Open Access Journals (Sweden)

Full Text Available Elevated sympathetic activation is a characteristic feature of heart failure (HF. Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow to the periphery in HF patients at rest and during exercise; however, because the firing occurrence of sympathetic activation is mainly synchronized by pulse pressure, multiunit MSNA, expressed as burst frequency (bursts/min and burst incidence (bursts/100heartbeats, may have limitations for the quantification of sympathetic nerve activity. In HF, multiunit MSNA is near the maximum level, and cannot increase further than the heartbeat. Single-unit MSNA analysis in humans is technically demanding, but provides more detailed information regarding central sympathetic firing. Although a great deal is known about the response of multiunit MSNA to stress, little information is available regarding the responses of single-unit MSNA to physiological stress and disease. The purposes of this review are to describe the differences between multiunit and single-unit MSNA during stress and to discuss the advantages of single-unit MSNA recording in improving our understanding the pathology of increased sympathetic activity in HF.

HISAYOSHIMURAI

2012-05-01

162

A comparative study of gland cells implicated in the nerve dependence of salamander limb regeneration.  

Science.gov (United States)

Limb regeneration in salamanders proceeds by formation of the blastema, a mound of proliferating mesenchymal cells surrounded by a wound epithelium. Regeneration by the blastema depends on the presence of regenerating nerves and in earlier work it was shown that axons upregulate the expression of newt anterior gradient (nAG) protein first in Schwann cells of the nerve sheath and second in dermal glands underlying the wound epidermis. The expression of nAG protein after plasmid electroporation was shown to rescue a denervated newt blastema and allow regeneration to the digit stage. We have examined the dermal glands by scanning and transmission electron microscopy combined with immunogold labelling of the nAG protein. It is expressed in secretory granules of ductless glands, which apparently discharge by a holocrine mechanism. No external ducts were observed in the wound epithelium of the newt and axolotl. The larval skin of the axolotl has dermal glands but these are absent under the wound epithelium. The nerve sheath was stained post-amputation in innervated but not denervated blastemas with an antibody to axolotl anterior gradient protein. This antibody reacted with axolotl Leydig cells in the wound epithelium and normal epidermis. Staining was markedly decreased in the wound epithelium after denervation but not in the epidermis. Therefore, in both newt and axolotl the regenerating axons induce nAG protein in the nerve sheath and subsequently the protein is expressed by gland cells, under (newt) or within (axolotl) the wound epithelium, which discharge by a holocrine mechanism. These findings serve to unify the nerve dependence of limb regeneration. PMID:20456522

Kumar, Anoop; Nevill, Graham; Brockes, Jeremy P; Forge, Andrew

2010-07-01

163

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

OpenAIRE

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...

Rahmouni, Kamal

2010-01-01

164

Long term effects on epileptiform activity with vagus nerve stimulation in children.  

OpenAIRE

Purpose: We report tong-term effects of vagus nerve stimulation (VNS) on epileptiform activity in 15 children, and how these changes are related to activity stage and to clinical effects on seizure reduction, seizure severity (NHS3) and quality of life (QOL). Methods: Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with 24 h ambulatory EEG monitoring for spike detection. The number of interictal epiteptiform discharges (IEDs) and the inter spike intervals (...

Hallbo?o?k, Tove; Lundgren, Johan; Blennow, Go?sta; Stro?mblad, Lars-go?ran; Rose?n, Ingmar

2005-01-01

165

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

Directory of Open Access Journals (Sweden)

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.

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

2009-03-01

166

Terminal Schwann cells participate in neuromuscular synapse remodeling during reinnervation following nerve injury.  

Science.gov (United States)

Schwann cells (SCs) at neuromuscular junctions (NMJs) play active roles in synaptic homeostasis and repair. We have studied how SCs contribute to reinnervation of NMJs using vital imaging of mice whose motor axons and SCs are transgenically labeled with different colors of fluorescent proteins. Motor axons most commonly regenerate to the original synaptic site by following SC-filled endoneurial tubes. During the period of denervation, SCs at the NMJ extend elaborate processes from the junction, as shown previously, but they also retract some processes from territory they previously occupied within the endplate. The degree of this retraction depends on the length of the period of denervation. We show that the topology of the remaining SC processes influences the branching pattern of regenerating axon terminals and the redistribution of acetylcholine receptors (AChRs). Upon arriving at the junction, regenerating axons follow existing SC processes within the old synaptic site. Some of the AChR loss that follows denervation is correlated with failure of portions of the old synaptic site that lack SC coverage to be reinnervated. New AChR clustering is also induced by axon terminals that follow SC processes extended during denervation. These observations show that SCs participate actively in the remodeling of neuromuscular synapses following nerve injury by their guidance of axonal reinnervation. PMID:24790203

Kang, Hyuno; Tian, Le; Mikesh, Michelle; Lichtman, Jeff W; Thompson, Wesley J

2014-04-30

167

Apamin reduces neuromuscular transmission by activating inhibitory muscarinic M(2) receptors on motor nerve terminals.  

Science.gov (United States)

This study was undertaken to investigate the mechanism by which the toxin from the bee venom, apamin, might exert beneficial effects in patients suffering from myotonic dystrophy. The effects of apamin were compared with those produced by another potassium channel blocker, 4-aminopyridine, on rat hemidiaphragm preparations stimulated at a 100 Hz frequency via the phrenic nerve. Apamin and 4-aminopyridine increased nerve-evoked tetanic fade without changing the maximal tetanic tension. The inhibitory effect of apamin was mimicked by acetylcholine. In contrast with apamin, 4-aminopyridine increased the amplitude of muscle contractions induced by nerve stimulation at 0.2 Hz frequency. All these compounds were devoid of effect when diaphragm muscle fibres were stimulated directly in the presence of the neuromuscular blocker, D-tubocurarine. The muscarinic M(2) receptor antagonist, methoctramine, prevented the inhibitory effects of both apamin and acetylcholine. Blockade of presynaptic facilitatory muscarinic M(1) and nicotinic receptors respectively with pirenzepine and hexamethonium increased apamin-induced tetanic fade. Data suggest that apamin inhibits neuromuscular transmission by a mechanism independent of the blockade of Ca(2+)-activated K(+) channels, which might involve the activation of inhibitory muscarinic M(2) receptors on motor nerve terminals. Such a mechanism may be the origin of the beneficial effect of apamin controlling muscle excitability in patients suffering from myotonic diseases. PMID:19818752

de Matos Silva, Ledyanne Francielle Casitas; de Paula Ramos, Edivan Rodrigo; Ambiel, Celia Regina; Correia-de-Sá, Paulo; Alves-Do-Prado, Wilson

2010-01-25

168

Differential effects of activity dependent treatments on axonal regeneration and neuropathic pain after peripheral nerve injury.  

Science.gov (United States)

Activity treatments are useful strategies to increase axonal regeneration and functional recovery after nerve lesions. They are thought to benefit neuropathy by enhancing neurotrophic factor expression. Nevertheless the effects on sensory function are still unclear. Since neurotrophic factors also play a fundamental role in peripheral and central sensitization, we studied the effects of acute electrical stimulation and early treadmill exercise on nerve regeneration and on neuropathic pain, and the relation with the expression of neurotrophins. After sciatic nerve section and suture repair, rats were subjected to electrical stimulation (ES) for 4h after injury, forced treadmill running (TR) for 5 days, or both treatments combined. Sciatic nerve section induced hyperalgesia in the medial area of the plantar skin in the injured paw. TR and ES differently but positively reduced adjacent neuropathic pain before and after sciatic reinnervation. ES enhanced motor and sensory reinnervation, and combination with TR induced strong agonistic effects in relieving pain. The differential effects of these activity treatments were related to changes in neurotrophic factor mRNA levels in sensory and motor neurons. ES speeded up expression of BDNF and GDNF in DRG, and of BDNF and NT3 in the ventral horn. TR reduced the levels of pro-nociceptive factors such as BDNF, NGF and GDNF in DRG. Combination of ES and TR induced intermediate levels suggesting an optimal balancing of treatment effects. PMID:23201096

Cobianchi, Stefano; Casals-Diaz, Laura; Jaramillo, Jessica; Navarro, Xavier

2013-02-01

169

Engineered neural tissue with aligned, differentiated adipose-derived stem cells promotes peripheral nerve regeneration across a critical sized defect in rat sciatic nerve.  

Science.gov (United States)

Adipose-derived stem cells were isolated from rats and differentiated to a Schwann cell-like phenotype in vitro. The differentiated cells (dADSCs) underwent self-alignment in a tethered type-1 collagen gel, followed by stabilisation to generate engineered neural tissue (EngNT-dADSC). The pro-regenerative phenotype of dADSCs was enhanced by this process, and the columns of aligned dADSCs in the aligned collagen matrix supported and guided neurite extension in vitro. EngNT-dADSC sheets were rolled to form peripheral nerve repair constructs that were implanted within NeuraWrap conduits to bridge a 15 mm gap in rat sciatic nerve. After 8 weeks regeneration was assessed using immunofluorescence imaging and transmission electron microscopy and compared to empty conduit and nerve graft controls. The proportion of axons detected in the distal stump was 3.5 fold greater in constructs containing EngNT-dADSC than empty tube controls. Our novel combination of technologies that can organise autologous therapeutic cells within an artificial tissue construct provides a promising new cellular biomaterial for peripheral nerve repair. PMID:25453954

Georgiou, Melanie; Golding, Jon P; Loughlin, Alison J; Kingham, Paul J; Phillips, James B

2015-01-01

170

Static muscle contraction reflexly increases adrenal sympathetic nerve activity in rats.  

Science.gov (United States)

Little is known about the mechanisms responsible for activation of sympathoadrenal function during exercise. We hypothesized that sympathoadrenal discharge is activated at the onset of exercise by a reflex arising in the contracting muscle. Adrenal sympathetic nerve activity (SNA) was recorded during 1 min stimulation of the tibial nerve at two times motor threshold, before and during neuromuscular blockade, in 12 alpha-chloralose-anesthetized rats. Static muscle contractions, induced by stimulation before neuromuscular blockade, were repeated during ganglionic blockade (n = 6) to specifically test reflex activation of preganglionic activity to the adrenal gland. During static contraction, adrenal SNA rapidly increased (P less than 0.05) to a maximum of 89 +/- 12% above basal and then declined, reaching basal levels after 30 s of muscle contraction. Tibial nerve stimulation during neuromuscular blockade had no effect on adrenal SNA. In most rats, adrenal SNA decreased with ganglionic blockade, indicating postganglionic as well as preganglionic innervation of the adrenal gland. During ganglionic blockade, static muscle contractions elicited a 140 +/- 21% increase in adrenal preganglionic SNA. In conclusion, static muscle contraction reflexly increases SNA to the adrenal gland, providing a mechanism for sympathoadrenal activation at the onset of exercise. PMID:1951780

Vissing, J; Wilson, L B; Mitchell, J H; Victor, R G

1991-11-01

171

A Silent Period of Levator Palpebrae Activity Induced By Median Nerve Stimulation  

Directory of Open Access Journals (Sweden)

Full Text Available Scientific Background: Levator palpebrae muscle is known to have a tonic activity which is inhibited in conditions where consciousness is lost. Therefore, there must be a direct relationship between ascending reticular activating system and nucleus of levator palpebrae in brainstem.Objectives: In this study, we have investigated electrophysiological clues related to this hypothesis. Material and Methods: We examined 6 patients with total peripheral-type facial palsy. A needle electromyogram electrode was used to record levator palpebrae muscle activity during median nerve stimulation. While the eyes were open, we stimulated the median nerve at the wrist with 0.5-1 msec. stimuli. We recorded the reflex activity of the levator palpebrae muscle.Results: We report that median stimulation produced a silent period with the duration of 25±4 msec. However, there was no similar silent period in the orbicularis oculi muscle with the stimulation of the median nerve in the normal side.Conclusions: This silent period may be an electrophysiological sign of the relationship between the ascending reticular activating system and the levator palpebrae muscle. Although this pattern was in fact an inhibitory type it could also be a polysynaptic reflex relationship of excitatory type since it leads to inhibition during sleep, as well.

Hilmi UYSAL

2010-03-01

172

Neuroprotection signaling pathway of nerve growth factor and brain-derived neurotrophic factor against staurosporine induced apoptosis in hippocampal H19-7 cells  

OpenAIRE

Neurotrophins protect neurons against excitotoxicity; however the signaling mechanisms for this protection remain to be fully elucidated. Here we report that activation of the phosphatidyl inositol 3 kinase (PI3K)/Akt pathway is critical for protection of hippocampal cells from staurosporine (STS) induced apoptosis, characterized by nuclear condensation and activation of the caspase cascade. Both nerve growth factor (NGF) and brain-derived growth factor (BDNF) prevent STS-induced apoptotic mo...

Nguyen, Truong Lx; Kim, Chung Kwon; Cho, Jun-hee; Lee, Kyung-hoon; Ahn, Jee-yin

2010-01-01

173

Matrix metalloproteinase-14 both sheds cell surface NG2 proteoglycan on macrophages and governs the response to peripheral nerve injury.  

Science.gov (United States)

Neuronal glial antigen 2 (NG2) is an integral membrane chondroitin sulfate proteoglycan, expressed by vascular pericytes, macrophages (NG2-M?) and progenitor glia of the nervous system. Herein, we revealed that NG2 shedding and axonal growth, either independently or jointly, depended on the pericellular remodeling events executed by membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14). Using purified NG2 ectodomain constructs, individual MMPs and primary NG2-M? cultures, we demonstrated, for the first time, that MMP-14 performed as an efficient and unconventional NG2 sheddase, and that NG2-M? infiltrated into the damaged PNS. We then characterized the spatio-temporal relationships among MMP-14, MMP-2, and TIMP-2 (tissue inhibitor of metalloproteinases-2) in sciatic nerve. TIMP-2-free MMP-14 was observed in the primary Schwann cell cultures using the inhibitory hydroxamate warhead-based MP-3653 fluorescent reporter. In teased nerve fibers, MMP-14 translocated post-injury towards the nodes of Ranvier and its substrates, laminin and NG2. Inhibition of MMP-14 activity, using the selective, function-blocking DX2400 human monoclonal antibody, increased the levels of regeneration-associated factors, including laminin, GAP-43 and ATF3, thereby promoting sensory axon regeneration after nerve crush. Concomitantly, DX2400 therapy attenuated mechanical hypersensitivity associated with nerve crush in rats. Together, our findings describe a new model in which MMP-14 proteolysis regulates the extracellular milieu and presents a novel therapeutic target in the damaged PNS and neuropathic pain. PMID:25488667

Nishihara, Tasusku; Remacle, Albert G; Angert, Mila; Shubayev, Igor; Shiryaev, Sergey A; Liu, Huaqing; Dolkas, Jennifer; Chernov, Andrei V; Strongin, Alex Y; Shubayev, Veronica I

2014-12-01

174

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

Science.gov (United States)

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

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

2015-02-01

175

Voltage-activated calcium currents in presynaptic nerve terminals of the chicken ciliary ganglion.  

Science.gov (United States)

1. Calcium currents (ICa) were recorded from presynaptic calyces of ciliary ganglia of the chick embryo under whole-cell voltage clamp. 2. Only high-threshold ICa was recorded without any evidence for the presence of low-threshold Ca2+ channels. 3. High-threshold (high-voltage-activated, HVA) ICa could be classified into non-inactivating (HVAn) and inactivating (HVAi) components. The mean inactivation time constant of the HVAi component was 213 ms (at 0 mV). The threshold for activation by depolarizing pulses was more negative for the HVAn component than for the HVAi component. The HVAi component was inactivated by 19% at a holding potential of -60 mV, while the HVAn component was little affected under this condition. 4. The activation of HVAn component was faster than that of the HVAi component. 5. Both the HVAn and HVAi components were blocked by Cd2+ (50 microM) and La3+ (1 microM). Both components were only slightly affected by Ni2+ (100 microM). The order of potency in blocking was La3+ greater than Cd2+ greater than Ni2+ for both components. Both the HVAi and HVAn components were irreversibly blocked by omega-conotoxin GVIA(omega-CgTX, 10 microM). 6. The two components could pharmacologically be distinguished by selective blockade of the HVAn component with nifedipine (2 microM) and D600 (100-250 microM). 7. HVAn and HVAi components are suggested to represent two different subpopulations of Ca2+ channels. The HVAn subpopulation may be responsible for persistent Ca2+ influx during subthreshold depolarization of the nerve terminal. PMID:2172522

Yawo, H

1990-09-01

176

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

Directory of Open Access Journals (Sweden)

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.

Christine Radtke

2012-10-01

177

Neural-differentiated mesenchymal stem cells incorporated into muscle stuffed vein scaffold forms a stable living nerve conduit.  

Science.gov (United States)

Autologous nerve grafts to bridge nerve gaps have donor site morbidity and possible neuroma formation resulting in development of various methods of bridging nerve gaps without using autologous nerve grafts. We have fabricated an acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells (MSCs) as a substitute for nerve autografts. Human vein and muscle were both decellularized by liquid nitrogen immersion with subsequent hydrolysis in hydrochloric acid. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid, and a combination of trophic factors. The differentiated MSCs were seeded on the surface of acellular muscle tissue and then stuffed into the vein. Our study showed that 35-75% of the cells expressed neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF receptor, and Nestin after differentiation. Histological and ultra structural analyses of muscle stuffed veins showed attachment of cells onto the surface of the acellular muscle and penetration of the cells into the hydrolyzed fraction of muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8 weeks post-implantation, the acellular muscle tissue had fully degraded and replaced with new matrix produced by the seeded cells. The vein was still intact and no inflammatory reactions were observed proving the biocompatibility and biodegradability of the conduit. In conclusion, we have successfully formed a stable living nerve conduit which may serve as a substitute for autologous nerves. PMID:22411691

Hassan, Nur Hidayah; Sulong, Ahmad Fadzli; Ng, Min-Hwei; Htwe, Ohnmar; Idrus, Ruszymah B H; Roohi, Sharifah; Naicker, Amaramalar S; Abdullah, Shalimar

2012-10-01

178

[Current knowledge on the formation of nitric oxide in endothelial cells of blood vessels, in nerve cells and macrophages as well as its significance in vascular dilatation, information transmission and damage of tumor cells].  

Science.gov (United States)

The vasculature endothelium cells and the nerve cells of several regions of the brain and the autonomous nerve system contain a nitric oxide (NO)-synthase, that forms NO from arginine. The NO-synthase is stimulated by bradykinin, histamine and acetylcholine and is especially active in the coronary and brain vessels. In the vasculature smooth muscle NO activates the guanylate cyclase: The increase in the concentration of cGMP induces a relaxation and in this way a vasodilatation. In the nerve cells NO is active as a neuromodulator. The activation of macrophages by gamma-interferon or by lipopolysaccharides induces the formation of a NO-synthase, that has other properties than the enzyme of the endothelium cells. The macrophages secrete NO and inhibit the metabolism of tumour cells, especially enzymes of the respiratory chain and of the citric acid cycle as well as the DNA-synthesis. Trinitroglycerin and amyl nitrite form with thiol-compounds S-nitroso-compounds, the decomposition of these forms NO. PMID:1719706

Kolb, E

1991-08-01

179

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

Science.gov (United States)

The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with ?-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. PMID:25056352

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

2014-09-15

180

Caffeine enhances modulation of parasympathetic nerve activity in humans: quantification using power spectral analysis.  

Science.gov (United States)

We investigated changes in autonomic nerve activity following caffeine intake by power spectral analysis of R-R intervals of heartbeats in humans. A beverage containing 240 mg of caffeine or a control beverage was given to 10 healthy volunteers, and R-R intervals were measured while subjects were sitting and controlling their respiration at a constant rate. After consumption of the caffeine-containing beverage, a transient and significant increase (P effect of caffeine was also examined using decaffeinated coffee supplemented with exogenous caffeine (2 mg/kg body wt). A transient and significant increase (P caffeine. The ratio of HC to total integrated value (which is also used as a selective indicator of vagal activity) was also significantly higher (P caffeine consumption. Physiological variables accompanying the change in autonomic nerve activity (i.e., blood pressure, surface body temperature and heart rate) were not significantly affected by caffeine intake. These results suggest that power spectral analysis of heartbeat R-R intervals is an effective and noninvasive method for detecting subtle changes in autonomic nerve activity in response to food intake. PMID:9202101

Hibino, G; Moritani, T; Kawada, T; Fushiki, T

1997-07-01

181

The effect of sodium nitroprusside on resting membrane potential of the leech Retzius nerve cells  

Directory of Open Access Journals (Sweden)

Full Text Available We have investigated the effect of sodium nitroprusside (SNP on the membrane resting potential of the leech (Haemopis sanguisuga Retzius nerve cells (RNC. The membrane potential of RNC of isolated ganglia was recorded in Ringer solution, in SNP solution during the next 30 minutes and after washing out with Ringer solution. We used 1 mmol/L, 2 mmol/L and 5 mmol/L solutions of SNP. Kruskal-Wallis ANOVA test was used to compare the fall of membrane potential of the leech Retzius nerve cells when different SNP concentrations were used. There was no change in the membrane resting potential of the leech Retzius nerve cells with 1 mmol/L concentration of SNP whilst 2 mmol/L concentration of SNP induced hyperpolarization during the first 20 minutes. The highest concentration of 5 mmol/L SNP induced hyperpolarization in 50% of cells during the first minute and during the next 10 minutes in the other 50%. The significant fall of membrane potential was recorded with 5mmol/L SNP concentration (p<0.05. The SNP induced hyperpolarization of RNC might be the effect of this NO donor on the potassium channels of leech RNC.

Stojanovi? Jasna

2006-01-01

182

An immortalized human blood-nerve barrier endothelial cell line for in vitro permeability studies.  

Science.gov (United States)

Solute and macromolecular transport studies may elucidate nutritional requirements and drug effects in healthy and diseased peripheral nerves. Endoneurial endothelial cells are specialized microvascular cells that form the restrictive blood-nerve barrier (BNB). Primary human endoneurial endothelial cells (pHEndECs) are difficult to isolate, limiting their widespread availability for biomedical research. We developed a simian virus-40 large T-antigen (SV40-LTA) immortalized human BNB cell line via stable transfection of low passage pHEndECs and observed continuous growth in culture for >45 population doublings. As observed with pHEndECs, the immortalized BNB endothelial cells were Ulex Europaeus agglutinin-1-positive and endocytosed low density lipoprotein, but lost von Willebrand factor expression. Glucose transporter-1, P-glycoprotein (P-gp), ?-glutamyl transpeptidase (?-GT), large neutral amino acid transporter-1 (LAT-1), creatine transporter (CRT), and monocarboxylate transporter-1 (MCT-1) mRNA expression were retained at all passages with loss of alkaline phosphatase (AP) expression after passages 16-20. Compared with an SV40-LTA immortalized human blood-brain barrier endothelial cell line, there was increased ?-GT protein expression, equivalent expression of organic anion transporting polypeptide-C (OATP-C), organic anion transporter 3 (OAT-3), MCT-1, and LAT-1, and reduced expression of AP, CRT, and P-gp by the BNB cell line at passage 20. Further studies demonstrated lower transendothelial electrical resistance (~181 vs. 191 ? cm(2)), equivalent permeability to fluoresceinated sodium (4.84 vs. 4.39 %), and lower permeability to fluoresceinated high molecular weight (70 kDa) dextran (0.39 vs. 0.52 %) by the BNB cell line. This cell line retained essential molecular and biophysical properties suitable for in vitro peripheral nerve permeability studies. PMID:23104242

Yosef, Nejla; Ubogu, Eroboghene E

2013-03-01

183

Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure  

OpenAIRE

Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patien...

Deo, Shekhar H.; Fisher, James P.; Vianna, Lauro C.; Kim, Areum; Chockalingam, Anand; Zimmerman, Matthew C.; Zucker, Irving H.; Fadel, Paul J.

2012-01-01

184

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

OpenAIRE

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...

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

2013-01-01

185

Influence of spontaneously occurring bursts of muscle sympathetic nerve activity on conduit artery diameter  

OpenAIRE

Large increases in muscle sympathetic nerve activity (MSNA) can decrease the diameter of a conduit artery even in the presence of elevated blood pressure, suggesting that MSNA acts to regulate conduit artery tone. Whether this influence can be extrapolated to spontaneously occurring MSNA bursts has not been examined. Therefore, we tested the hypothesis that MSNA bursts decrease conduit artery diameter on a beat-by-beat basis during rest. Conduit artery responses were assessed in the brachial ...

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

2013-01-01

186

Uridine 5?-Triphosphate Promotes In Vitro Schwannoma Cell Migration through Matrix Metalloproteinase-2 Activation  

OpenAIRE

In response to peripheral nerve injury, Schwann cells adopt a migratory phenotype and modify the extracellular matrix to make it permissive for cell migration and axonal re-growth. Uridine 5?-triphosphate (UTP) and other nucleotides are released during nerve injury and activate purinergic receptors expressed on the Schwann cell surface, but little is known about the involvement of purine signalling in wound healing. We studied the effect of UTP on Schwannoma cell migration and wound closure...

Lamarca, Aloa; Gella, Alejandro; Martian?ez, Tania; Segura, Mo?nica; Figueiro-silva, Joana; Grijota-martinez, Carmen; Trullas, Ramo?n; Casals, Nu?ria

2014-01-01

187

BNIP3 Regulates AT101 [(-)-Gossypol] Induced Death in Malignant Peripheral Nerve Sheath Tumor Cells  

OpenAIRE

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived sarcomas and are the leading cause of mortality in patients with neurofibromatosis type 1 (NF1). Current treatment modalities have been largely ineffective, resulting in a high rate of MPNST recurrence and poor five-year patient survival. This necessitates the exploration of alternative chemotherapeutic options for MPNST patients. This study sought to assess the cytotoxic effect of the BH3-mimetic AT101 [(-)...

Kaza, Niroop; Kohli, Latika; Graham, Christopher D.; Klocke, Barbara J.; Carroll, Steven L.; Roth, Kevin A.

2014-01-01

188

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

OpenAIRE

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...

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

2008-01-01

189

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

Directory of Open Access Journals (Sweden)

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.

Gao Li-Zhi

2009-12-01

190

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)

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.

João G Franca

2014-10-01

191

Vagus nerve stimulation magnet activation for seizures: a critical review.  

Science.gov (United States)

Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation. PMID:25145652

Fisher, R S; Eggleston, K S; Wright, C W

2015-01-01

192

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

OpenAIRE

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...

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

2012-01-01

193

Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats  

OpenAIRE

Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brain stem. Expiration is a passive process except for special metabolic conditions such as hypercapnia, when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase...

Molkov, Yaroslav I.; Zoccal, Daniel B.; Moraes, Davi J. A.; Paton, Julian F. R.; Machado, Benedito H.; Rybak, Ilya A.

2011-01-01

194

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

OpenAIRE

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...

Hara, K.; Floras, J. S.

1996-01-01

195

Differential distribution of muscle and skin sympathetic nerve activity in patients with end-stage renal disease  

OpenAIRE

End-stage renal disease (ESRD) is characterized by resting sympathetic overactivity. Baseline muscle sympathetic nerve activity (MSNA), which is governed by baroreflexes and chemoreflexes, is elevated in ESRD. Whether resting skin sympathetic nerve activity (SSNA), which is independent from baroreflex and chemoreflex control, is also elevated has never been reported in renal failure. The purpose of this study was to determine whether sympathetic overactivity of ESRD is generalized to include ...

Park, Jeanie; Campese, Vito M.; Nobakht, Niloofar; Middlekauff, Holly R.

2008-01-01

196

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.)

197

Nerve Growth Factor Stimulates the Concentration of TrkA within Lipid Rafts and Extracellular Signal-Regulated Kinase Activation through c-Cbl-Associated Protein?  

OpenAIRE

Nerve growth factor (NGF) acts through its receptor, TrkA, to elicit the neuronal differentiation of PC12 cells through the action of extracellular signal-regulated kinase 1 (ERK1) and ERK2. Upon NGF binding, TrkA translocates and concentrates in cholesterol-rich membrane microdomains or lipid rafts, facilitating formation of receptor-associated signaling complexes, activation of downstream signaling pathways, and internalization into endosomes. We have investigated the mechanisms responsible...

Limpert, Allison S.; Karlo, J. Colleen; Landreth, Gary E.

2007-01-01

198

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

Directory of Open Access Journals (Sweden)

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.

Yan Zhang

2014-10-01

199

Selective neural activation in a histologically derived model of peripheral nerve  

Science.gov (United States)

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.

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

2011-06-01

200

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

Directory of Open Access Journals (Sweden)

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.

Gemes Geza

2012-06-01

201

Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration.  

Science.gov (United States)

Nerve conduits are a proven strategy for guiding axon regrowth following injury. This study compares degradable silk-trehalose films containing chondroitinase ABC (ChABC) and/or glial cell line-derived neurotrophic factor (GDNF) loaded within a silk fibroin-based nerve conduit in a rat sciatic nerve defect model. Four groups of silk conduits were prepared, with the following silk-trehalose films inserted into the conduit: (a) empty; (b) 1?µg GDNF; (3) 2 U ChABC; and (4) 1?µg GDNF/2 U ChABC. Drug release studies demonstrated 20% recovery of GDNF and ChABC at 6?weeks and 24?h, respectively. Six conduits of each type were implanted into 15?mm sciatic nerve defects in Lewis rats; conduits were explanted for histological analysis at 6?weeks. Tissues stained with Schwann cell S-100 antibody demonstrated an increased density of cells in both GDNF- and ChABC-treated groups compared to empty control conduits (p?cell migration and proliferation and also foster axonal regeneration when repairing peripheral nerve gap defects. Silk fibroin-based nerve conduits possess favourable mechanical and degradative properties and are further enhanced when loaded with ChABC and GDNF. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25424415

Sivak, Wesley N; White, James D; Bliley, Jacqueline M; Tien, Lee W; Liao, Han Tsung; Kaplan, David L; Marra, Kacey G

2014-11-25

202

Impulse activity evokes precocious sprouting of nociceptive nerves into denervated skin.  

Science.gov (United States)

We have studied the sprouting of intact high-threshold mechanosensory nerves into adjacent denervated trunk skin in adult rats behaviorally, histologically, and electrophysiologically. In the anesthetized animal, stimulation of high-threshold endings in back skin by localized pinching elicits a bilateral reflex excitation of the underlying skeletal muscle, the cutaneous trunci muscle (CTM), visible as a twitch-like puckering of the skin. The reflex was also evoked by electrical excitation of A delta and of C fibers in the dorsal cutaneous nerves (DCNs), with characteristic latencies of 7-20 msec and 40-60 msec, respectively; excitation of low-threshold (A alpha) fibers was ineffective. After cutting selected DCNs, the deprived skin became insensible, but pinch responsiveness gradually recovered over the following 2 weeks. Regeneration of cut axons was not responsible for this recovery; when neighboring intact DCNs were cut, however, all responses were abolished in the recovered skin that had been initially denervated. By 3-5 days after denervation, axons in the dermis were all histologically absent or degenerating; when pinch sensitivity was restored to such skin, silver-stainable axons reappeared in the formerly empty Schwann tubes. During the work we noticed that the periodic examination by pinching, used to follow the time course of recovery of function in individual animals, led to an earlier development of this recovery than in animals that were examined only once at a specified time after denervation. This apparent acceleration in the redevelopment of pinch sensitivity was correlated with the appearance of axons in the recovered skin, and was shown to be due to the impulse activity evoked in the remaining nerves by the periodic pinching; it did not occur when the nerves were blocked by tetrodotoxin (TTX), and it was mimicked by a brief (10-min) period of electrical excitation of the A delta fibers in a remaining nerve carried out at the time when the denervation of skin was done. The time course of the phenomenon suggested that the principal effect of the impulses was to shorten the latency to the onset of sprouting in the activated A delta axons; that is, they induced precocious sprouting. The impulses needed to be conducted centrally for the effect to occur, and precocious sprouting failed to occur if the impulses were allowed to proceed only distally toward the skin. It seems that a brief conditioning burst of impulses in A delta axons sensitizes the neurons to the influence of a sprouting stimulus that appears when skin is denervated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:6098949

Nixon, B J; Doucette, R; Jackson, P C; Diamond, J

1984-01-01

203

Adenosine 5?-triphosphate and its relationship with other mediators that activate pelvic nerve afferent neurons in the rat colorectum  

OpenAIRE

Evidence of a role for purinergic signalling in visceral afferents involving P2X2, P2X3 and P2Y1 receptors exists, which appears to be important during inflammation. This study aimed to evaluate the degree of interaction between adenosine 5?-triphosphate (ATP) and other mediators that activate sensory nerves in the colorectum. Recordings from pelvic nerve afferents were made during application of agents to the in-vitro colorectal preparation. Analysis allowed calculation of single unit acti...

Wynn, Gregory; Burnstock, Geoffrey

2006-01-01

204

Schwann Cells Overexpressing FGF-2 Alone or Combined with Manual Stimulation Do Not Promote Functional Recovery after Facial Nerve Injury  

OpenAIRE

Purpose. To determine whether transplantation of Schwann cells (SCs) overexpressing different isoforms of fibroblast growth factor 2 (FGF-2) combined with manual stimulation (MS) of vibrissal muscles improves recovery after facial nerve transection in adult rat. Procedures. Transected facial nerves were entubulated with collagen alone or collagen plus naïve SCs or transfected SCs. Half of the rats received daily MS. Collateral branching was quantified from motoneuron counts after retrogr...

Haastert, Kirsten; Grosheva, Maria; Angelova, Srebrina K.; Guntinas-lichius, Orlando; Skouras, Emmanouil; Michael, Joern; Grothe, Claudia; Dunlop, Sarah A.; Angelov, Doychin N.

2009-01-01

205

Therapeutic Effect of Myogenic Cells Modified to Express Neurotrophic Factors in a Rat Model of Sciatic Nerve Injury  

OpenAIRE

Sciatic nerve injury may cause neurological deficits, particularly muscle weakness. Previous studies have shown that administration of neurotrophic factors (NTFs), naturally occurring proteins that support the development and survival of neurons, partially protected the damaged motor neuron in the injured sciatic nerve. In the current study, we have examined whether the administration of various combinations of transfected muscle progenitor cells (MPCs) populations, each expressing a single N...

Dadon- Nachum, M.; Ben-zur, T.; Srugo, I.; Shamir, H. M.; Melamed, E.; Yaffe, D.; Offen, D.

2012-01-01

206

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

OpenAIRE

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...

KennethSShindler; LingZuo; MiraMSachdeva

2012-01-01

207

Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor.  

Science.gov (United States)

New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age- and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) A?1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects. PMID:25147108

Ferreira, Daniel; Westman, Eric; Eyjolfsdottir, Helga; Almqvist, Per; Lind, Göran; Linderoth, Bengt; Seiger, Ake; Blennow, Kaj; Karami, Azadeh; Darreh-Shori, Taher; Wiberg, Maria; Simmons, Andrew; Wahlund, Lars-Olof; Wahlberg, Lars; Eriksdotter, Maria

2015-01-01

208

Transgenic inhibition of astroglial NF-?B protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Optic neuritis is an acute, demyelinating neuropathy of the optic nerve often representing the first appreciable symptom of multiple sclerosis. Wallerian degeneration of irreversibly damaged optic nerve axons leads to death of retinal ganglion cells, which is the cause of permanent visual impairment. Although the specific mechanisms responsible for triggering these events are unknown, it has been suggested that a key pathological factor is the activation of immune-inflammatory processes secondary to leukocyte infiltration. However, to date, there is no conclusive evidence to support such a causal role for infiltrating peripheral immune cells in the etiopathology of optic neuritis. Methods To dissect the contribution of the peripheral immune-inflammatory response versus the CNS-specific inflammatory response in the development of optic neuritis, we analyzed optic nerve and retinal ganglion cells pathology in wild-type and GFAP-I?B?-dn transgenic mice, where NF-?B is selectively inactivated in astrocytes, following induction of EAE. Results We found that, in wild-type mice, axonal demyelination in the optic nerve occurred as early as 8?days post induction of EAE, prior to the earliest signs of leukocyte infiltration (20?days post induction. On the contrary, GFAP-I?B?-dn mice were significantly protected and showed a nearly complete prevention of axonal demyelination, as well as a drastic attenuation in retinal ganglion cell death. This correlated with a decrease in the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, as well as a prevention of NAD(PH oxidase subunit upregulation. Conclusions Our results provide evidence that astrocytes, not infiltrating immune cells, play a key role in the development of optic neuritis and that astrocyte-mediated neurotoxicity is dependent on activation of a transcriptional program regulated by NF-?B. Hence, interventions targeting the NF-?B transcription factor in astroglia may be of therapeutic value in the treatment of optic neuritis associated with multiple sclerosis.

Brambilla Roberta

2012-09-01

209

Upregulated expression of ebp1 contributes to schwann cell differentiation and migration after sciatic nerve crush.  

Science.gov (United States)

Ebp1, an ErbB3-binding protein, is the human homologue of the cell cycle-regulated mouse protein p38-2G4. Ebp1 was reported to inhibit the proliferation and induce the differentiation of human cancer cells. Its p48 isoform contributes to neuronal differentiation and growth factor specificity. However, the expression and role of Ebp1 in peripheral system lesions and repair are still unknown. Herein, we investigated the spatiotemporal pattern of Ebp1 expression following sciatic nerve crush. After crush, the level of Ebp1 protein was elevated gradually, peaked at day 5, and then declined to the normal at 4 weeks, which was similar to the expression of Oct-6. Furthermore, using double immunofluorescent staining, we found Ebp1 had a colocalization with S100 and Oct-6 in 5-day injured tissues. In vitro, we observed enhanced expression of Ebp1 during the process of cyclic adenosine monophosphate (cAMP)-induced Schwann cells differentiation. Interestingly, Ebp1-depleted SCs did not show significant morphologic change after the treatment of cAMP. Also, we observed a colocalization between Ebp1 and Cyclin D1 and that Ebp1-specific siRNA-transfected SCs had a decreased migration. Taken together, we speculated that Ebp1 was upregulated in the sciatic nerve after crush, which was involved in the differentiation and migration of Schwann cells. PMID:24878627

Liu, Yang; Liu, Yonghua; Cao, Jianhua; Zhu, Xiaojian; Nie, Xiaoke; Yao, Li; Chen, Minhao; Cheng, Xinghai; Wang, Youhua

2014-12-01

210

BNIP3 Regulates AT101 [(-)-Gossypol] Induced Death in Malignant Peripheral Nerve Sheath Tumor Cells  

Science.gov (United States)

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived sarcomas and are the leading cause of mortality in patients with neurofibromatosis type 1 (NF1). Current treatment modalities have been largely ineffective, resulting in a high rate of MPNST recurrence and poor five-year patient survival. This necessitates the exploration of alternative chemotherapeutic options for MPNST patients. This study sought to assess the cytotoxic effect of the BH3-mimetic AT101 [(-)-gossypol] on MPNST cells in vitro and to identify key regulators of AT101-induced MPNST cell death. We found that AT101 caused caspase-independent, non-apoptotic MPNST cell death, which was accompanied by autophagy and was mediated through HIF-1? induced expression of the atypical BH3-only protein BNIP3. These effects were mediated by intracellular iron chelation, a previously unreported mechanism of AT101 cytotoxicity. PMID:24824755

Kaza, Niroop; Kohli, Latika; Graham, Christopher D.; Klocke, Barbara J.; Carroll, Steven L.; Roth, Kevin A.

2014-01-01

211

Multiple acute effects on the membrane potential of PC12 cells produced by nerve growth factor (NGF).  

Science.gov (United States)

We studied whether nerve growth factor (NGF) can affect the membrane potential and conductance of PC12 cells. We demonstrate that NGF depolarizes the membrane of PC12 cells within a minute and by using transfected NIH 3T3-Trk and -p75 cells we show that both the high affinity NGF receptor p140(trk) and the low affinity NGF receptor or p75(NGF) may be involved in the depolarization. Tyrosine kinase inhibitor, K252a, partially inhibited the depolarization, but two agents affecting intracellular calcium movements, Xestospongin C (XeC) and thapsigargin, did not. The early depolarization was eliminated in Na+ free solutions and under this condition, a 'prolonged' (> 2 min) hyperpolarization was observed in PC12 cells in response to NGF. This hyperpolarization was also induced in PC12 cells by epidermal growth factor (EGF). Voltage clamp experiments showed that NGF produced a late (> 2 min) increase in membrane conductance. The Ca2+-dependent BK-type channel blocker, iberiotoxin, and the general Ca2+-dependent K+ channel blocker, TEA, attenuated or eliminated the hyperpolarization produced by NGF in sodium free media. Under pretreatment with the non-selective cation channel blockers La3+ and Gd3+, NGF hyperpolarized the membrane of PC12 cells. These results suggest that three different currents are implicated in rapid NGF-induced membrane voltage changes, namely an acutely activated Na+ current, Ca2+-dependent potassium currents and non-selective cation currents. PMID:15729735

Shimazu, Kazuhiro; Takeda, Kazuyo; Yu, Zu-Xi; Jiang, Hao; Liu, Xu-Wen; Nelson, Phillip G; Guroff, Gordon

2005-06-01

212

Sickle cell disease in mice is associated with sensitization of sensory nerve fibers.  

Science.gov (United States)

The pain phenotype in sickle cell disease (SCD) patients is highly variable. A small percentage of SCD patients experience many vaso-occlusive crises/year, 5% of patients account for over 30% of pain episodes, while 39% report few episodes of severe pain. Clearly, a better understanding of the pathobiology of SCD is needed to improve its therapy. Humanized sickle cell mice recapitulate several phenotypes of SCD patients and provide a model for the study of SCD pain. Researchers have shown that one strain of humanized SCD mice, the BERK strain, has abnormal pain phenotype. However, the nociception phenotype of another humanized SCD mouse strain, the Townes strain, has not been described. In a large cross-sectional study of BERK and Townes SCD mice, we examined thermosensory response and sensory nerve fiber function using sine-wave electrical stimulation at 2000, 250, and 5?Hz to stimulate preferentially A?, A?, and C sensory nerve fibers, respectively. We found that BERK and Townes mice, compared to respective controls, had decreases in 2000, 250, and 5?Hz current vocalization thresholds in patterns that suggest sensitization of a broad spectrum of sensory nerve fibers. In addition, the pattern of sensitization of sensory fibers varied according to strain, sex, age, and mouse genotype. In a similarly variable pattern, Townes and BERKs also had significantly altered sensitivity to noxious thermal stimuli in agreement with what has been shown by others. In summary, the analysis of somatosensory function using sine-wave electrical stimulation in humanized sickle cell mice suggests that in SCD, both myelinated and unmyelinated, fibers are sensitized. The pattern of sensory fiber sensitization is distinct from that observed in pain models of neuropathic and inflammatory pain. These findings raise the possibility that sensitization of a broad spectrum of sensory fibers might contribute to the altered and variable nociception phenotype in SCD. PMID:25070860

Kenyon, Nicholas; Wang, Li; Spornick, Nicholas; Khaibullina, Alfia; Almeida, Luis Ef; Cheng, Yao; Wang, Jichuan; Guptill, Virginia; Finkel, Julia C; Quezado, Zenaide Mn

2015-01-01

213

Neonatal superior ovarian nerve transection disturbs the cyclic activity of the female rats.  

Science.gov (United States)

The neural pathway most related with ovarian steroidogenesis has been identified as the superior ovarian nerve (SON). This work constitutes the first study of the effects of early ovarian SON transection, which was performed in rats of 4 days of age (SON-t rats) to magnify the effects of the denervation. The rats were studied at the prepubertal (30 days), peripubertal (41 days) and adult cyclic in dioestrus (60 days) reproductive stages. The SON-t rats showed a delay of vaginal opening, a notable disruption of oestrous cyclicity, and a large number of corpora lutea. In all the stages, the circulating levels of FSH, prolactin and growth hormone were lower in SON-t rats than in controls, whereas LH did not vary. Serum androstenedione levels were higher in SON-t rats at 30 days and lower at 41 days, compared with control animals while no difference was observed at 60 days. Serum progesterone levels did not differ between control and SON-t, but serum oestradiol concentrations were higher in SON-t rats in all of the stages. At the peripubertal stage, there were fewer ovarian beta-adrenergic receptors in SON-t ovaries, associated with a rise in the ovarian content of norepinephrine, but no changes were observed in SON-t rats at 30 and 60 days with respect to the controls. The release of progesterone in vitro from luteal cell in SON-t rats at 60 days was reduced in basal condition and under ovine LH or FSH stimulation, when compared with control animals; while no difference was observed in presence of isoproterenol or androstenedione in the culture medium. In corpora lutea of SON-t rats at 60 days, no change was observed in the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), but the activity of 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) was reduced, suggesting abnormal luteolysis in spite of the large number of corpora lutea. The interruption of innervation at an early age by SON transection is very important in the regulation of ovarian development in prepubertal and cyclic rats. The functional changes observed in the ovary suggest a possible alteration in the hypothalamic-hypophyseal axis. PMID:12429141

Forneris, Myriam L; Aguado, Luis I

2002-09-01

214

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure  

Energy Technology Data Exchange (ETDEWEB)

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

Halbrook, R.S.; Shugart, L.R.; Watson, A.P.; Munro, N.B.; Linnabary, R.D. (Environmental Sciences Division, Oak Ridge National Laboratory, TN (United States))

1992-09-01

215

Pinched Nerve  

Science.gov (United States)

NINDS Pinched Nerve Information Page Table of Contents (click to jump to sections) What is Pinched Nerve? Is there any treatment? ... being done? Clinical Trials Organizations What is Pinched Nerve? The term "pinched nerve" is a colloquial term ...

216

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

Science.gov (United States)

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 pressure was unaffected in both groups. Muscimol reduced burst frequency of phrenic nerve activity (P 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

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

2014-09-01

217

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1988-09-01

218

Radioautographic characterization of a serotonin-accumulating nerve cell group in adult rat hypothalamus  

International Nuclear Information System (INIS)

Intensely labeled nerve cell bodies were identified by radioautography within the pars ventralis of nucleus dorsomedialis hypothalami (hdv), following intraventricular perfusion with 10-5 or 10-4 M tritiated serotonin [3H]5-HT in adult rats pretreated with a monoamine oxidase inhibitor. This selective reaction, which involved approximately 1000 neurons on each side of the third ventricle, was unaltered by concomitant administration of 10-3 M non-radioactive norepinephrine, and was absent after intraventricular injection of 10-5 or 10-4 M tritiated norepinephrine. The 3H-labeled 5-HT nerve cell bodies were loosely grouped within the inner and caudal half of the hdv, and appeared morphologically similar to the unreactive neurons among which they were interspersed. Within the same region, numerous labeled axonal varicosities were also detected which were never found in synaptic contact with the reactive cells. If the 3H-labeled 5-HT neurons endogenous 5-HT, they might constitute an intrinsic source of 5-HT innervation in the adult rat hypothalamus. (Auth.)

219

Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6 and the neurotrophin (NT Nerve Growth Factor (NGF for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold, regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold, growth differentiation factor 15 (GDF15; 80-fold, platelet-derived growth factor alpha (PDGFA; 69-fold, growth hormone releasing hormone (GHRH; 30-fold, adenylate cyclase activating polypeptide (PACAP; 20-fold and hepatocyte growth factor (HGF; 5-fold. NGF recruits GDF15 (131-fold, transforming growth factor beta 1 (TGFB1; 101-fold and brain-derived neurotrophic factor (BDNF; 89-fold. Both stimuli activate growth-associated protein 43 (GAP-43 indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold and early growth response 1 (Egr1/Zif268; 3-fold known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell adhesion, small molecule biochemistry aiming at changing intracellular concentrations of second messengers such as Ca2+ and cAMP as well as expression of enzymes involved in posttranslational modification of proteins. Conclusion The current data provide novel candidate genes involved in neuronal differentiation, notably for the neuropoietic cytokine IL-6. Our findings may also have impact on the clinical treatment of peripheral nerve injury. Local application of a designer cytokine such as H-IL-6 with drastically enhanced bioactivity in combination with NTs may generate a potent reparative microenvironment.

Dimitriades-Schmutz Beatrice

2009-02-01

220

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

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...

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

221

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

Directory of Open Access Journals (Sweden)

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.

Raven Mary A

2008-07-01

222

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

Directory of Open Access Journals (Sweden)

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.

Dwaipayan Sen

2013-10-01

223

Crosstalk between delta opioid receptor and nerve growth factor signaling modulates neuroprotection and differentiation in rodent cell models.  

Science.gov (United States)

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. PMID:24152443

Sen, Dwaipayan; Huchital, Michael; Chen, Yulong L

2013-01-01

224

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

Science.gov (United States)

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

Sulaiman, O A; Gordon, T

2000-12-01

225

Muscarinic Acetylcholine Receptor Subtype Expression in Avian Vestibular Hair Cells, Nerve Terminals and Ganglion Cells  

OpenAIRE

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the central and peripheral nervous systems and play an important role in modulating the cell activity and function. We have shown that the cholinergic agonist carbachol reduces the pKir2.1 ionic currents in native vestibular hair cells. We have cloned and sequenced pigeon mAChR subtypes M2–M5 and we have studied the expression of all five mAChR subtypes (M1–M5) in the pigeon vestibular end organs (semicircular canal ampul...

Li, Gang Q.; Kevetter, Golda A.; Leonard, Robert B.; Prusak, Deborah J.; Wood, Thomas G.; Correia, Manning J.

2007-01-01

226

Identification of two nerve growth factor-induced polypeptides in PC12 cells.  

Science.gov (United States)

We have identified two nerve growth factor (NGF)-induced polypeptides (Mr 80,000 and 90,000) in PC12 cells that are heat stable and not sulfated. Indirect immunofluorescence localization of these polypeptides in NGF-treated PC12 cells reveals a punctate pattern concentrated in neurites. Immunoperoxidase staining of rat tissue shows that these polypeptides are found throughout the brain in selected subsets of neurons and are absent in the pituitary or adrenal medulla. Several of these characteristics are similar to a recently described NGF-induced secretory protein (VGF8a), which has sequence similarities to secretogranins. The property of NGF inducibility and the distribution of these polypeptides within rat tissues are both novel features for secretogranin proteins. PMID:2275847

Sussman, M A; Battenberg, E; Bloom, F E; Fowler, V M

1990-01-01

227

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

Science.gov (United States)

Complete serial sectioning of the medulla oblongata in monkey, cat, guinea pig, and japanese dancing mouse and incubation for somatostatin-immunoreaction was carried out. Numerous regions of the medulla oblongata such as the nucleus reticularis gigantocellularis, nucleus cuneatus et gracillis, nucleus raphe magnus, nucleus tractus solitarius, nucleus vestibularis, and parts of the oliva contain dense networks of somatostatin-immunoreactive nerve fibers. Cell bodies were seen in the nucleus reticularis medullae oblongatae. In the spinal cord the sections from each segment were analyzed, showing the highest concentrations of somatostatinergic fibers in the substantia gelantinosa of the columna dorsalis. Cell bodies were seen in the zona intermedia centralis, especially in the upper cervical segments. Many positive fibers were also seen in the entire zona intermedia and the columna ventralis. Especially prominent was the immunoreactivity in the zona intermediolateralis of the thoracic segments and the columna ventralis of the lower lumbar and sacral segments. PMID:390039

Forssmann, W G; Burnweit, C; Shehab, T; Triepel, J

1979-10-01

228

Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity  

Science.gov (United States)

The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training (n = 9), sham training (n = 7), or control (n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1 mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg), heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.

Ray, C. A.; Carrasco, D. I.

2000-01-01

229

Characterization of the peri-implant epithelium in hamster palatine mucosa: behavior of Merkel cells and nerve endings.  

Science.gov (United States)

The purpose of this study was to investigate the relationship between Merkel cells and nerve elements during tissue regeneration after receiving dental implants. Golden hamsters were divided into 3 groups and titanium alloy implants were fixed in their left-side maxilla through the third palatine rug. Animals were sacrificed at 1, 2, 3, 4, 5, 6, and 7 days after the implantation and tissues were characterized at the immunohistochemical and morphological levels. CK 20 and PGP 9.5 antibodies which react with Merkel cells and nerve fibers were used. Immunohistochemically, no CK 20-positive Merkel cells were seen in the peri-implant epithelium throughout the 7 days. However, starting at day 4, PGP 9.5-positive nerve fibers appeared in the connective tissue, and by day 7, nerve fibers had invaded the more superficial layer of the peri-implant epithelium compared to the mucosa removal control group. At the electron microscopic level, the intercellular spaces of the regenerating epithelium in the mucosa removal control group were small. In contrast, intercellular spaces of the peri-implant epithelium tended to be wide and regenerating nerve fibers invaded those intercellular spaces. In both the mucosa removal control group and the implantation group, the basal lamina and connective tissues regenerated completely. However, clear Merkel cells containing neurosecretory granules were not observed. Taken together, our results indicate that Merkel cells in the hamster palatine mucosa do not regenerate in the peri-implant epithelium. However, regenerative nerve fibers seem to play essential roles as part of the defense and sensory systems around the peri-implant epithelium to compensate for the weakened defense mechanism. PMID:16415507

Suzuki, Yuta; Matsuzaka, Kenichi; Ishizaki, Ken; Tazaki, Masakazu; Sato, Toru; Inoue, Takashi

2005-12-01

230

Altered Active Zones, Vesicle Pools, Nerve Terminal Conductivity, and Morphology during Experimental MuSK Myasthenia Gravis  

Science.gov (United States)

Recent studies demonstrate reduced motor-nerve function during autoimmune muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). To further understand the basis of motor-nerve dysfunction during MuSK-MG, we immunized female C57/B6 mice with purified rat MuSK ectodomain. Nerve-muscle preparations were dissected and neuromuscular junctions (NMJs) studied electrophysiologically, morphologically, and biochemically. While all mice produced antibodies to MuSK, only 40% developed respiratory muscle weakness. In vitro study of respiratory nerve-muscle preparations isolated from these affected mice revealed that 78% of NMJs produced endplate currents (EPCs) with significantly reduced quantal content, although potentiation and depression at 50 Hz remained qualitatively normal. EPC and mEPC amplitude variability indicated significantly reduced number of vesicle-release sites (active zones) and reduced probability of vesicle release. The readily releasable vesicle pool size and the frequency of large amplitude mEPCs also declined. The remaining NMJs had intermittent (4%) or complete (18%) failure of neurotransmitter release in response to 50 Hz nerve stimulation, presumably due to blocked action potential entry into the nerve terminal, which may arise from nerve terminal swelling and thinning. Since MuSK-MG-affected muscles do not express the AChR ? subunit, the observed prolongation of EPC decay time was not due to inactivity-induced expression of embryonic acetylcholine receptor, but rather to reduced catalytic activity of acetylcholinesterase. Muscle protein levels of MuSK did not change. These findings provide novel insight into the pathophysiology of autoimmune MuSK-MG. PMID:25438154

Patel, Vishwendra; Oh, Anne; Voit, Antanina; Sultatos, Lester G.; Babu, Gopal J.; Wilson, Brenda A.; Ho, Mengfei; McArdle, Joseph J.

2014-01-01

231

Association of nerve growth factor receptors with the triton X-100 cytoskeleton of PC12 cells  

International Nuclear Information System (INIS)

Triton X-100 solubilizes membranes of PC12 cells and leaves behind a nucleus and an array of cytoskeletal filaments. Nerve growth factor (NGF) receptors are associated with this Triton X-100-insoluble residue. Two classes of NGF receptors are found on PC12 cells which display rapid and slow dissociating kinetics. Although rapidly dissociating binding is predominant (greater than 75%) in intact cells, the majority of binding to the Triton X-100 cytoskeleton is slowly dissociating (greater than 75%). Rapidly dissociating NGF binding on intact cells can be converted to a slowly dissociating form by the plant lectin wheat germ agglutinin (WGA). This lectin also increases the number of receptors which associate with the Triton X-100 cytoskeleton by more than 10-fold. 125I-NGF bound to receptors can be visualized by light microscopy autoradiography in Triton X-100-insoluble residues of cell bodies, as well as growth cones and neurites. The WGA-induced association with the cytoskeleton, however, is not specific for the NGF receptor. Concentrations of WGA which change the Triton X-100 solubility of membrane glycoproteins are similar to those required to alter the kinetic state of the NGF receptor. Both events may be related to the crossbridging of cell surface proteins induced by this multivalent lectin

232

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

DEFF Research Database (Denmark)

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.

Witting, Nanna; Kupers, Ron

2006-01-01

233

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

Directory of Open Access Journals (Sweden)

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.

MariaJBarnes

2014-08-01

234

Silent Squamous Cell Carcinoma Invading the Orbit Following the Course of the Zygomaticotemporal Nerve.  

Science.gov (United States)

Abstract Purpose: To evaluate the clinical and histopathological characteristics of silent skin squamous cell carcinomas (SCC) with invasion routes to the orbit. Methods: Retrospective case studies. Clinical records and histopathological material, therapy and complications were evaluated, together with MRI imaging analyses and literature review on the anatomy of the lateral orbital wall in relation to the zygomatico-temporal nerve channel. Results: Two recent cases of metastatic SCC from het lateral zygomatic region to het orbit are reported. Originally the skin tumors of the first case was diagnosed as benign, but a review of the pathology of these skin tumors showed an invasive SCC. The second case was diagnosed as an atypical SCC. Analysis of possible invasion routes, using both computer tomography (CT) and magnetic resonance imaging (MRI), indicated neither skin nor bone involvement. However, the lateral temporal fossa near the entrance of the zygomatico-temporal channel showed small tumors and pseudo-cysts. The original skin tumor specimens did not show malignant tissue in the surgical margins nor intra- or perineural invasion. Conclusions: Because the course of the zygomatico-temporal nerve bundle was exactly in line with the original skin tumor, the channel and the orbital tumors, this route should be considered when malignant orbital tumors have a history of or a relation with a periorbital skin-tumor. PMID:25264716

de Keizer, Ronald O B; de Wolff-Rouendaal, Didi; de Keizer, Rob J W

2014-09-29

235

The pan erbB inhibitor PD168393 enhances lysosomal dysfunction-induced apoptotic death in malignant peripheral nerve sheath tumor cells  

Science.gov (United States)

Malignant peripheral nerve sheath tumors (MPNSTs) are rapidly progressive Schwann cell neoplasms. The erbB family of membrane tyrosine kinases has been implicated in MPNST mitogenesis and invasion and, thus, is a potential therapeutic target. However, tyrosine kinase inhibitors (TKIs) used alone have limited tumoricidal activity. Manipulating the autophagy lysosomal pathway in cells treated with cytostatic agents can promote apoptotic cell death in some cases. The goal of this study was to establish a mechanistic basis for formulating drug combinations to effectively trigger death in MPNST cells. We assessed the effects of the pan erbB inhibitor PD168393 on MPNST cell survival, caspase activation, and autophagy. PD168393 induced a cytostatic but not a cytotoxic response in MPNST cells that was accompanied by suppression of Akt and mTOR activation and increased autophagic activity. The effects of autophagy modulation on MPNST survival were then assessed following the induction of chloroquine (CQ)–induced lysosomal stress. In CQ-treated cells, suppression of autophagy was accompanied by increased caspase activation. In contrast, increased autophagy induction by inhibition of mTOR did not trigger cytotoxicity, possibly because of Akt activation. We thus hypothesized that dual targeting of mTOR and Akt by PD168393 would significantly increase cytotoxicity in cells exposed to lysosomal stress. We found that PD168393 and CQ in combination significantly increased cytotoxicity. We conclude that combinatorial therapies with erbB inhibitors and agents inducing lysosomal dysfunction may be an effective means of treating MPNSTs. PMID:22259051

Kohli, Latika; Kaza, Niroop; Lavalley, Nicholas J.; Turner, Kathryn L.; Byer, Stephanie; Carroll, Steven L.; Roth, Kevin A.

2012-01-01

236

Oncomodulin links inflammation to optic nerve regeneration  

OpenAIRE

The inflammatory response that accompanies central nervous system (CNS) injury can affect neurological outcome in both positive and negative ways. In the optic nerve, a CNS pathway that normally fails to regenerate when damaged, intraocular inflammation causes retinal ganglion cells (RGCs) to switch into an active growth state and extend lengthy axons down the nerve. The molecular basis of this phenomenon is uncertain. A prior study showed that oncomodulin (Ocm), a Ca2+-binding protein secret...

Yin, Yuqin; Cui, Qi; Gilbert, Hui-ya; Yang, Yang; Yang, Zhiyong; Berlinicke, Cynthia; Li, Zhiwei; Zaverucha-do-valle, Camila; He, Huamei; Petkova, Victoria; Zack, Donald J.; Benowitz, Larry I.

2009-01-01

237

Edaravone promotes functional recovery after mechanical peripheral nerve injury.  

Science.gov (United States)

Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expression was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechanical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression. PMID:25374594

Zhang, Teng; Li, Zhengwei; Dong, Jianli; Nan, Feng; Li, Tao; Yu, Qing

2014-09-15

238

Internalization of nerve growth factor by pheochromocytoma PC12 cells: absence of transfer to the nucleus  

International Nuclear Information System (INIS)

The intracellular distribution of 125I-labeled nerve growth factor (NGF) in rat pheochromocytoma PC12 cells was studied by quantitative electron microscopic (EM) autoradiography and by subcellular fractionation. PC12 cells were grown as monolayer cultures in medium supplemented with serum in the presence of 125I-NGF. EM autoradiography showed that 125I-NGF was localized at the plasma membrane and cytoplasmic compartments but did not accumulate in the nuclear chromatin or in the nuclear membrane compartment of cells analyzed after 1 hr and 1, 2, and 8 d of incubation with 125I-NGF. 125I-NGF also was not detected in nuclear subcellular fractions prepared from cells grown in serum-supplemented medium either in suspension for 1 d or in monolayer cultures for 1 to 8 d. In contrast, and in confirmation of the results of Yankner and Shooter, about 60% of the cell-bound 125I-NGF was found in the nuclear pellet after cell fractionation if the cells had been kept previously in suspension for 1 d in phosphate-buffered saline supplemented with 0.2% glucose, 0.1% bovine serum albumin, and 125I-NGF. The ultrastructure of PC12 cells grown under such conditions, however, revealed signs of varying degrees of damage. Autoradiography of the nuclear pellet from these cells showed the grains to be located mainly over damaged nuclei or over cell debris between nuclei. It is concluded that NGF, after binding to spes concluded that NGF, after binding to specific receptors at the plasma membrane, is transferred to membrane-confined cytoplasmic compartments but does not have to be transferred further to the nuclear membrane or to the nuclear chromatin as a prerequisite for its physiological action

239

Properties of internally perfused, voltage-clamped, isolated nerve cell bodies.  

Science.gov (United States)

The membrane properties of isolated neurons from Helix aspersa were examined by using a new suction pipette method. The method combines internal perfusion with voltage clamp of nerve cell bodies separated from their axons. Pretreatment with enzymes such as trypsin that alter membrane function is not required. A platinized platinum wire which ruptures the soma membrane allows low resistance access directly to the cell's interior improving the time resolution under voltage clamp by two orders of magnitude. The shunt resistance of the suction pipette was 10-50 times the neuronal membrane resistance, and the series resistance of the system, which was largely due to the tip diameter, was about 10(5) omega. However, the peak clamp currents were only about 20 nA for a 60-mV voltage step so that measurements of membrane voltage were accurate to within at least 3%. Spatial control of voltage was achieved only after somal separation, and nerve cell bodies isolated in this way do not generate all-or-none action potentials. Measurements of membrane potential, membrane resistance, and membrane time constant are equivalent to those obtained using intracellular micropipettes, the customary method. With the axon attached, comparable all-or-none action potentials were also measured by either method. Complete exchange of Cs+ for K+ was accomplished by internal perfusion and allowed K+ currents to be blocked. Na+ currents could then be blocked by TTX or suppressed by Tris-substituted snail Ringer solution. Ca2+ currents could be blocked using Ni2+ and other divalent cations as well as organic Ca2+ blockers. The most favorable intracellular anion was aspartate-, and the sequence of favorability was inverted from that found in squid axon. PMID:660159

Lee, K S; Akaike, N; Brown, A M

1978-05-01

240

Long-term Delivery of Nerve Growth Factor by Encapsulated Cell Biodelivery in the Göttingen Minipig Basal Forebrain  

OpenAIRE

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 geneti...

Fjord-larsen, Lone; Kusk, Philip; Tornøe, Jens; Juliusson, Bengt; Torp, Malene; Bjarkam, Carsten R.; Nielsen, Mette S.; Handberg, Aase; Sørensen, Jens Christian H.; Wahlberg, Lars U.

2010-01-01

241

Exposure to TMT odor affects adrenal sympathetic nerve activity and behavioral consequences in rats.  

Science.gov (United States)

The odor of 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a synthetic compound isolated from fox feces, induces various emotional behavioral and stress responses. Here we examined the effect of TMT on behavioral responses and adrenal sympathetic nerve activity (ASNA) in rats. TMT increased freezing behavior, defensive-burying and defensive-attack, and decreased exploration, grooming and approach behaviors. On the other hand, butyric acid (BA), a pungent but non-predatory odor, increased defensive-burying only. TMT increased ASNA strongly, whereas the effects of BA increased ASNA extremely weakly. Furthermore, pre-treatment with the histaminergic H1-receptor antagonist diphenhydramine eliminated the effects of TMT on ASNA. These findings suggest that TMT odor affects autonomic neurotransmission via histaminergic neurons. Exposure to TMT odor likely regulates the controlling autonomic function and output to a motor system simultaneously, evoking behavioral stress responses. PMID:20595033

Horii, Yuko; Nikaido, Yoshikazu; Nagai, Katsuya; Nakashima, Toshihiro

2010-12-25

242

Nerve growth factor improves the muscle regeneration capacity of muscle stem cells in dystrophic muscle.  

Science.gov (United States)

Researchers have attempted to use gene- and cell-based therapies to restore dystrophin and alleviate the muscle weakness that results from Duchenne muscular dystrophy (DMD). Our research group has isolated populations of muscle-derived stem cells (MDSCs) from the postnatal skeletal muscle of mice. In comparison with satellite cells, MDSCs display an improved transplantation capacity in dystrophic mdx muscle that we attribute to their ability to undergo long-term proliferation, self-renewal, and multipotent differentiation, including differentiation toward endothelial and neuronal lineages. Here we tested whether the use of nerve growth factor (NGF) improves the transplantation efficiency of MDSCs. We used two methods of in vitro NGF stimulation: retroviral transduction of MDSCs with a CL-NGF vector and direct stimulation of MDSCs with NGF protein. Neither method of NGF treatment changed the marker profile or proliferation behavior of the MDSCs, but direct stimulation with NGF protein significantly reduced the in vitro differentiation ability of the cells. NGF stimulation also significantly enhanced the engraftment efficiency of MDSCs transplanted within the dystrophic muscle of mdx mice, resulting in the regeneration of numerous dystrophin-positive muscle fibers. These findings highlight the importance of NGF as a modulatory molecule, the study of which will broaden our understanding of its biologic role in the regeneration and repair of skeletal muscle by musclederived cells. PMID:16454652

Lavasani, Mitra; Lu, Aiping; Peng, Hairong; Cummins, James; Huard, Johnny

2006-02-01

243

Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells.  

Science.gov (United States)

The optimal source of stem cells for regenerative medicine is a major question. Embryonic stem (ES) cells have shown promise for pluripotency but have ethical issues and potential to form teratomas. Pluripotent stem cells have been produced from skin cells by either viral-, plasmid- or transposon-mediated gene transfer. These stem cells have been termed induced pluripotent stem cells or iPS cells. iPS cells may also have malignant potential and are inefficiently produced. Embryonic stem cells may not be suited for individualized therapy, since they can undergo immunologic rejection. To address these fundamental problems, our group is developing hair follicle pluripotent stem (hfPS) cells. Our previous studies have shown that mouse hfPS cells can differentiate to neurons, glial cells in vitro, and other cell types, and can promote nerve and spinal cord regeneration in vivo. hfPS cells are located above the hair follicle bulge in what we have termed the hfPS cell area (hfPSA) and are nestin positive and keratin 15 (K-15) negative. Human hfPS cells can also differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In the present study, human hfPS cells were transplanted in the severed sciatic nerve of the mouse where they differentiated into glial fibrillary-acidic-protein (GFAP)-positive Schwann cells and promoted the recovery of pre-existing axons, leading to nerve generation. The regenerated nerve recovered function and, upon electrical stimulation, contracted the gastrocnemius muscle. The hfPS cells can be readily isolated from the human scalp, thereby providing an accessible, autologous and safe source of stem cells for regenerative medicine that have important advantages over ES or iPS cells. PMID:19507228

Amoh, Yasuyuki; Kanoh, Maho; Niiyama, Shiro; Hamada, Yuko; Kawahara, Katsumasa; Sato, Yuichi; Hoffman, Robert M; Katsuoka, Kensei

2009-08-01

244

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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.

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

2014-05-30

245

Comparison of Longitudinal In Vivo Measurements of Retinal Nerve Fiber Layer Thickness and Retinal Ganglion Cell Density after Optic Nerve Transection in Rat  

Science.gov (United States)

Purpose To determine the relationship between longitudinal in vivo measurements of retinal nerve fiber layer thickness (RNFLT) and retinal ganglion cell (RGC) density after unilateral optic nerve transection (ONT). Methods Nineteen adult Brown-Norway rats were studied; N?=?10 ONT plus RGC label, N?=?3 ONT plus vehicle only (sans label), N?=?6 sham ONT plus RGC label. RNFLT was measured by spectral domain optical coherence tomography (SD-OCT) at baseline then weekly for 1 month. RGCs were labeled by retrograde transport of fluorescently conjugated cholera toxin B (CTB) from the superior colliculus 48 hours prior to ONT or sham surgery. RGC density measurements were obtained by confocal scanning laser ophthalmoscopy (CSLO) at baseline and weekly for 1 month. RGC density and reactivity of microglia (anti-Iba1) and astrocytes (anti-GFAP) were determined from post mortem fluorescence microscopy of whole-mount retinae. Results RNFLT decreased after ONT by 17% (pRGC density decreased after ONT by 18%, 69%, 85% and 92% at weeks 1, 2, 3 and 4 (pRGC density measured in vivo at week 4 and post mortem by microscopy were strongly correlated (R?=?0.91, pRGC density were strongly correlated (R?=?0.81, pRGC density are strongly correlated and can be used to monitor longitudinal changes after optic nerve injury. The strong fellow eye effect observed in eyes contralateral to ONT, only in the presence of CTB label, consisted of a dramatic increase in RNFLT associated with retinal microgliosis. PMID:25393294

Choe, Tiffany E.; Abbott, Carla J.; Piper, Chelsea; Wang, Lin; Fortune, Brad

2014-01-01

246

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)

247

Appropriate modulation of autophagy sensitizes malignant peripheral nerve sheath tumor cells to treatment with imatinib mesylate.  

Science.gov (United States)

Malignant peripheral nerve sheath tumor (MPNST), very rare in childhood, is a highly aggressive soft-tissue tumor. We experienced a case of a 7-year-old boy with MPNST who was treated with imatinib mesylate (imatinib) after the identification of platelet-derived growth factor receptor expression in his tumor. We were unable to observe clinical benefits of imatinib in this patient. Therefore, cellular reactions of imatinib were investigated in vitro using 3 MPNST cell lines. Imatinib induced cytotoxicity in vitro with variable IC50 values (11.7 to >30 ?M). Induction of apoptosis was not a pivotal mechanism in the inhibitory effects. We found that the treatment of MPNST cell lines with imatinib induced autophagy. Suppression of the initiation of autophagy by 3-methyladenine or small interfering RNA (siRNA) against beclin-1 attenuated the imatinib-mediated cytotoxicity. In contrast, blocking the formation of autophagosomes or the development of autolysosomes using siRNA against microtubule-associated protein light chain 3B, bafilomycin A1, chloroquine, or an MEK1/2 inhibitor (U0126) enhanced the imatinib-induced cytotoxicity in MPNST cells. Our data showed that the imatinib-mediated autophagy can function as a cytotoxic mechanism and that appropriate modulation of autophagy may sensitize MPNST cells to imatinib, which in turn may be a novel therapeutic strategy for MPNST. PMID:24136016

Okano, Munehiro; Sakata, Naoki; Ueda, Satoshi; Takemura, Tsukasa

2014-04-01

248

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

Science.gov (United States)

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

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

2014-11-01

249

Diabetic Schwann cells suffer from nerve growth factor and neurotrophin-3 underproduction and poor associability with axons.  

Science.gov (United States)

Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs also provide a microenvironment favoring neural regeneration partially due to production of several neurotrophic factors. Dysfunction of SCs may also play an important role in the pathogenesis of peripheral nerve diseases such as diabetic peripheral neuropathy where hyperglycemia is often considered pathogenic. In order to study the impact of diabetes mellitus (DM) upon the regenerative capacity of adult SCs, we investigated the differential production of the neurotrophic factors nerve growth factor (NGF) and neurotrophin-3 (NT3) by SCs harvested from the sciatic nerves of murine models of type 1 DM (streptozotocin treated C57BL/6J mice) and type 2 DM (LepR(-/-) or db/db mice) or non-diabetic cohorts. In vitro, SCs from diabetic and control mice were maintained under similar hyperglycemic and euglycemic conditions respectively. Mature SCs from diabetic mice produced lower levels of NGF and NT3 under hyperglycemic conditions when compared to SCs in euglycemia. In addition, SCs from both DM and non-DM mice appear to be incapable of insulin production, but responded to exogenous insulin with greater proliferation and heightened myelination potentiation. Moreover, SCs from diabetic animals showed poorer association with co-cultured axons. Hyperglycemia had significant impact upon SCs, potentially contributing to the pathogenesis of diabetic peripheral neuropathy. PMID:24123456

Dey, Indranil; Midha, Nisha; Singh, Geeta; Forsyth, Amanda; Walsh, Sarah K; Singh, Bhagat; Kumar, Ranjan; Toth, Cory; Midha, Rajiv

2013-12-01

250

Sciatic nerve regeneration induced by transplantation of in vitro bone marrow stromal cells into an inside-out artery graft in rat.  

Science.gov (United States)

Traumatic injury to peripheral nerves results in considerable motor and sensory disability. Several research groups have tried to improve the regeneration of traumatized nerves by invention of favorable microsurgery. Effect of undifferentiated bone marrow stromal cells (BMSCs) combined with artery graft on peripheral nerve regeneration was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using an artery graft (IOAG) filled with undifferentiated BMSCs (2 × 10(7) cells/mL). In control group, the graft was filled with phosphated buffer saline alone. The regenerated fibers were studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was based on behavioral, functional (Walking Track Analysis), electrophysiological, histomorphometric and immuohistochemical (Schwann cell detection by S-100 expression) criteria. The behavioral, functional and electrophysiological studies confirmed significant recovery of regenerated axons in IOAG/BMSC group (P < 0.05). Quantitative morphometric analyses of regenerated fibers showed the number and diameter of myelinated fibers in IOAG/BMSC group were significantly higher than in the control group (P < 0.05). This demonstrates the potential of using undifferentiated BMSCs combined with artery graft in peripheral nerve regeneration without limitations of donor-site morbidity associated with isolation of Schwann cells. It is also cost saving due to reduction in interval from tissue collection until cell injection, simplicity of laboratory procedures compared to differentiated BMSCs and may have clinical implications for the surgical management of patients after facial nerve transection. PMID:24942097

Mohammadi, Rahim; Vahabzadeh, Behnam; Amini, Keyvan

2014-10-01

251

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

Science.gov (United States)

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 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.

Elisabet Stener-Victorin (Institution of Neuroscience and Physiology); Elizabeth Jeder (Osher Center for Integrative Medicine); Per Olaf Janson (inst. neuroscience and physiology); Yrsa Bergmann Sverrisdottir (inst. neuroscience and physiology)

2009-06-03

252

Muscle pain perception and sympathetic nerve activity to exercise during opioid modulation  

Science.gov (United States)

The purpose of this experiment was to examine the effects of the endogenous opioid system on forearm muscle pain and muscle sympathetic nerve activity (MSNA) during dynamic fatiguing exercise. Twelve college-age men (24 +/- 4 yr) performed graded (1-min stages; 30 contractions/min) handgrip to fatigue 1 h after the ingestion of either 60 mg codeine, 50 mg naltrexone, or placebo. Pain (0-10 scale) and exertion (0-10 and 6-20 scales) intensities were measured during the last 15 s of each minute of exercise and every 15 s during recovery. MSNA was measured continuously from the peroneal nerve in the left leg. Pain threshold occurred earlier [1.8 +/- 1, 2. 2 +/- 1, 2.2 +/- 1 J: codeine, naltrexone, and placebo, respectively] and was associated with a lower rating of perceived exertion (RPE) (2.7 +/- 2, 3.6 +/- 2, 3.8 +/- 2: codeine, naltrexone, and placebo, respectively) in the codeine condition compared with either the naltrexone or placebo conditions. There were no main effects (i.e., drugs) or interaction (i.e., drugs x time) for either forearm muscle pain or RPE during exercise [pain: F (2, 22) = 0.69, P = 0.51]. There was no effect of drug on MSNA, heart rate, or blood pressure during baseline, exercise, or recovery. Peak exercise MSNA responses were 21 +/- 1, 21 +/- 2.0, and 21 +/- 2.0 bursts/30 s for codeine, naltrexone, and placebo conditions, respectively. Peak mean arterial pressure responses were 135 +/- 4, 131 +/- 3, and 132 +/- 4 mmHg for codeine, naltrexone, and placebo conditions, respectively. It is concluded that neither 60 mg codeine nor 50 mg naltrexone has an effect on forearm muscle pain, exertion, or MSNA during high- intensity handgrip to fatigue.

Cook, D. B.; O'Connor, P. J.; Ray, C. A.

2000-01-01

253

Mechanism of Sphingosine 1-Phosphate- and Lysophosphatidic Acid-Induced Up-Regulation of Adhesion Molecules and Eosinophil Chemoattractant in Nerve Cells  

OpenAIRE

The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P1–5 and LPA1–3 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 Gi coupled receptors S1P1, S1P3, LPA1, LPA2 and LPA3 were expressed on IMR-32 cells...

Costello, Richard W.; Maloney, Michael; Atiyeh, Mazin; Gleich, Gerald; Walsh, Marie-therese

2011-01-01

254

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

OpenAIRE

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...

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

255

T cell memory in the injured facial motor nucleus: Relation to functional recovery following facial nerve crush  

OpenAIRE

T cells have the ability to mount a memory response to a previously encountered antigen such that re-exposure to the antigen results in a response that is greater in magnitude and function. Following facial nerve transection, T cells have been shown to traffic to injured motor neurons in the facial motor nucleus (FMN) and may have the ability to promote neuronal survival and functional recovery. Previously, we demonstrated that early exposure to neuronal injury on one side of the brain during...

Ha, Grace K.; Pastrana, Marlon; Huang, Zhi; Petitto, John M.

2008-01-01

256

Regulation of Nerve Growth Factor Release by Nitric Oxide through Cyclic GMP Pathway in Cortical Glial Cells  

OpenAIRE

In the present study, we found that S-nitroso-N-acetyl-dl-penicillamine, a spontaneous nitric oxide (NO) generator, dose-dependently inhibited basal nerve growth factor (NGF) release from mixed glial cells. To elucidate the function of endogenous NO in the regulation of NGF release, the mixed glial cells were stimulated with lipopolysaccharide (LPS) or LPS plus interfer-on-? (IFN?). The results showed that LPS alone induced NGF release and moderate NO production. However, costimulation with...

Xiong, Huabao; Yamada, Kiyofumi; Jourdi, Hussam; Kawamura, Meiko; Takei, Nobuyuki; Han, Daiken; Nabeshima, Toshitaka; Nawa, Hiroyuki

1999-01-01

257

Effects of capsaicin on KCl-induced blood flow and sensory nerve activity changes in the tooth pulp.  

Science.gov (United States)

Potassium ion-containing solutions have been shown to initially excite then depress intradental nerve activity (INA) when applied into deep dentinal cavities. The INA reflects activity originating in intradental A fibers. Application of KCl to deep dentinal cavities also induces an increase in pulpal blood flow (PBF). Capsaicin is known to exert a highly selective desensitizing effect on polymodal C-fiber nerve endings. These C fibers are generally believed to release vasoactive substances in response to stimulation. In order to determine if KCl exerts its vascular effect via activation of capsaicin-sensitive nerve fibers, we examined blood flow and sensory nerve responses to KCl obtained before and after capsaicin desensitization. The A-fiber nerve activity was determined by using INA recording technique. Blood flow was measured simultaneously from the same tooth using laser Doppler flowmetry. Local application of 0.25 M KCl to a deep dentinal cavity induced a brief spike burst and an increase in PBF of 76.0 +/- 14.6% (n = 8). Repeated applications of 0.25 M KCl caused a consistent increase in the peak PBF amplitude (n = 8). Local application of 100 microM capsaicin to a deep dentinal cavity caused an increase in PBF of 116.8 +/- 26.3% (n = 8) lasting 12-18 min, but capsaicin application did not appear to evoke any INA response. The amplitude of PBF in response to capsaicin application declined during repeated applications. Following repeated applications of capsaicin the PBF response to KCl was significantly reduced (9.9 +/- 4.3%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8460053

Pertl, C; Liu, M T; Markowitz, K; Kim, S

1993-03-01

258

Light microscopic image analysis system to quantify immunoreactive terminal area apposed to nerve cells  

Science.gov (United States)

The present report describes a desktop computer-based method for the quantitative assessment of the area occupied by immunoreactive terminals in close apposition to nerve cells in relation to the perimeter of the cell soma. This method is based on Fast Fourier Transform (FFT) routines incorporated in NIH-Image public domain software. Pyramidal cells of layer V of the somatosensory cortex outlined by GABA immunolabeled terminals were chosen for our analysis. A Leitz Diaplan light microscope was employed for the visualization of the sections. A Sierra Scientific Model 4030 CCD camera was used to capture the images into a Macintosh Centris 650 computer. After preprocessing, filtering was performed on the power spectrum in the frequency domain produced by the FFT operation. An inverse FFT with filter procedure was employed to restore the images to the spatial domain. Pasting of the original image to the transformed one using a Boolean logic operation called 'AND'ing produced an image with the terminals enhanced. This procedure allowed the creation of a binary image using a well-defined threshold of 128. Thus, the terminal area appears in black against a white background. This methodology provides an objective means of measurement of area by counting the total number of pixels occupied by immunoreactive terminals in light microscopic sections in which the difficulties of labeling intensity, size, shape and numerical density of terminals are avoided.

Wu, L. C.; D'Amelio, F.; Fox, R. A.; Polyakov, I.; Daunton, N. G.

1997-01-01

259

Bone marrow cells produce nerve growth factor and promote angiogenesis around transplanted islets  

Directory of Open Access Journals (Sweden)

Full Text Available AIM: To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/c mice were transplanted syngeneically under the kidney capsule with the following: (1 200 islets (islet group: n = 12, (2 1-5 × 106 bone marrow cells (bone marrow group: n = 11, (3 200 islets and 1-5 × 106 bone marrow cells (islet + bone marrow group: n = 13, or (4 no cells (sham group: n = 5. All mice were evaluated for blood glucose, serum insulin, serum nerve growth factor (NGF and glucose tolerance (GTT up to postoperative day (POD 14. Histological assessment for insulin, von Willebrand factor (vWF and NGF was performed at POD 3, 7 and 14.RESULTS: Blood glucose level was lowest and serum insulin was highest in the islet + bone marrow group. Serum NGF increased in islet, bone marrow, and islet + bone marrow groups after transplantation, and there was a significant difference (P = 0.0496, ANOVA between the bone marrow and sham groups. The number of vessels within the graft area was significantly increased in both the bone marrow and islet + bone marrow groups at POD 14 as compared to the islet alone group (21.2 ± 3.6 in bone marrow, P = 0.01, vs islet group, 22.6 ± 1.9 in islet + bone marrow, P = 0.0003, vs islet group, 5.3 ± 1.6 in islet-alone transplants. NGF was more strongly expressed in bone marrow cells compared with islets.CONCLUSION: Bone marrow cells produce NGF and promote angiogenesis. Islet co-transplantation with bone marrow is associated with improvement of islet graft function.

Naoaki Sakata, Nathaniel K Chan, John Chrisler, Andre Obenaus, Eba Hathout

2010-03-01

260

Microtubules and Microfilaments in Fixed and Permeabilized Cells are Selectively Decorated by Nerve Growth Factor  

Science.gov (United States)

A specific antibody against nerve growth factor (NGF) and indirect immunofluorescence microscopy have been used to follow the in vitro binding of NGF to cells made permeable to large molecules. All cells tested, both target (sensory neurons and PC12 cells) and nontarget (3T3, BKH 2I, C6 glioma cells), revealed a decoration of cytoskeletal structures which on the basis of their form, reactivity with antibodies, and sensitivity to specific drugs may be identified as microtubules (MTs) and microfilaments (MFs). The decoration of either structure depends on the fixation and permeabilization conditions: MFs, in the form of stress fibers, are stained by NGF when the plasma membrane is permeabilized with methanol/acetone; MTs become intensely stained when the plasma membrane is solubilized with a nonionic detergent in the presence of a MT-stabilizing medium. The two procedures do not affect the staining of these structures with specific antibodies. Binding of 125I-labeled NGF to PC12 cells was not competitively inhibited by a 100-fold excess of several positively charged proteins but it was markedly decreased in the presence of DNase I. 125I-Labeled NGF interacted with MTs and F-actin (fixed with paraformaldehyde) in a range of concentrations similar to that used for their cellular localization with NGF-anti-NGF. Our studies show that the specificity and affinity of NGF binding to MTs and MFs is in the range of that of antibodies against tubulin and actin. The possible relevance of these findings to the mechanism of action of NGF in target cells is discussed.

Nasi, S.; Cirillo, D.; Naldini, L.; Marchisio, P. C.; Calissano, P.

1982-02-01

261

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors.  

Science.gov (United States)

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n = 7), or a diuretic, hydrochlorothiazide (n = 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P bursts (100 beats)(-1) pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)(-1); P = 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)(-1)), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)(-1); P = 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P = 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r = 0.74, P = 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin-angiotensin-aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients. PMID:24060993

Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Bivens, Tiffany B; Adams-Huet, Beverley; Levine, Benjamin D; Fu, Qi

2013-12-01

262

Region-specific changes in sympathetic nerve activity in angiotensin II–salt hypertension in the rat  

OpenAIRE

It is now well accepted that many forms of experimental hypertension and human essential hypertension are caused by increased activity of the sympathetic nervous system. However, the role of region-specific changes in sympathetic nerve activity (SNA) in the pathogenesis of hypertension has been difficult to determine because methods for chronic measurement of SNA in conscious animals have not been available. We have recently combined indirect, and continuous and chronic direct, assessment of ...

Osborn, John W.; Fink, Gregory D.

2009-01-01

263

Nerves and Anesthesia: A physics perspective on medicine  

CERN Document Server

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...

Heimburg, Thomas

2014-01-01

264

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.

265

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

Energy Technology Data Exchange (ETDEWEB)

Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} 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.

Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

2010-07-16

266

Protein Kinase C? Mediates Neurogenic but Not Mitogenic Activation of Mitogen-Activated Protein Kinase in Neuronal Cells  

OpenAIRE

In several neuronal cell systems, fibroblast-derived growth factor (FGF) and nerve growth factor (NGF) act as neurogenic agents, whereas epidermal growth factor (EGF) acts as a mitogen. The mechanisms responsible for these different cellular fates are unclear. We report here that although FGF, NGF, and EGF all activate mitogen-activated protein (MAP) kinase (extracellular signal-related kinase [ERK]) in rat hippocampal (H19-7) and pheochromocytoma (PC12) cells, the activation of ERK by the ne...

Corbit, Kevin C.; Foster, David A.; Rosner, Marsha Rich

1999-01-01

267

Neurofibromin specific antibody differentiates malignant peripheral nerve sheath tumors (MPNST) from other spindle cell neoplasms.  

Science.gov (United States)

Malignant peripheral nerve sheath tumors (MPNST) derive from the Schwann cell or perineurial cell lineage and occur either sporadically or in association with the tumor syndrome neurofibromatosis type 1 (NF1). MPNST often pose a diagnostic challenge due to their frequent lack of pathognomonic morphological or immunohistochemical features. Mutations in the NF1 tumor suppressor gene are found in all NF1-associated and many sporadic MPNST. The presence of NF1 mutation may have the potential to differentiate MPNST from several morphologically similar neoplasms; however, mutation detection is hampered by the size of the gene and the lack of mutational hot spots. Here we describe a newly developed monoclonal antibody binding to the C-terminus of neurofibromin (clone NFC) which was selected for optimal performance in routinely processed formalin-fixed and paraffin-embedded tissue. NFC immunohistochemistry revealed loss of neurofibromin in 22/25 (88 %) of NF1-associated and 26/61 (43 %) of sporadic MPNST. There was a strong association of neurofibromin loss with deletions affecting the NF1 gene (P neurofibromin in 2/8 myxofibrosarcomas, 2/12 (16 %) pleomorphic liposarcomas, 1/16 (6 %) leiomyosarcomas, and 4/28 (14 %) unclassified undifferentiated pleomorphic sarcomas. However, loss of neurofibromin was not observed in 22 synovial sarcomas, 27 schwannomas, 23 solitary fibrous tumors, 14 low-grade fibromyxoid sarcomas, 50 dedifferentiated liposarcomas, 27 myxoid liposarcomas, 13 angiosarcomas, 9 extraskeletal myxoid chondrosarcomas, and 7 epitheloid sarcomas. Immunohistochemistry using antibody NFC may substantially facilitate sarcoma research and diagnostics. PMID:24464231

Reuss, David E; Habel, Antje; Hagenlocher, Christian; Mucha, Jana; Ackermann, Ulrike; Tessmer, Claudia; Meyer, Jochen; Capper, David; Moldenhauer, Gerhard; Mautner, Victor; Frappart, Pierre-Olivier; Schittenhelm, Jens; Hartmann, Christian; Hagel, Christian; Katenkamp, Kathrin; Petersen, Iver; Mechtersheimer, Gunhild; von Deimling, Andreas

2014-04-01

268

Malignant peripheral nerve cell sheath tumour of the upper lip: a rare case  

Directory of Open Access Journals (Sweden)

Full Text Available We present the case of a malignant peripheral nerve sheath tumour (MPNST that developed on the upper lip of an 86 year old woman. MPNSTs are highly aggressive sarcomas that very rarely occur in the face. We know of no other reported cases of a malignant peripheral nerve sheath tumour arising from the upper lip.

Joseph Ward

2010-07-01

269

Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death.  

Science.gov (United States)

Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperitoneal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reached the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-immunoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2'-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death. PMID:25422633

Yan, Bing Chun; Park, Joon Ha; Chen, Bai Hui; Cho, Jeong-Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae-Chul; Hwang, In Koo; Cho, Jun Hwi; Lee, Yun Lyul; Kang, Il-Jun; Won, Moo-Ho

2014-10-01

270

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese 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.

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

271

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

OpenAIRE

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...

Visvader, J.; Sassone-corsi, P.; Verma, I. M.

1988-01-01

272

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

Directory of Open Access Journals (Sweden)

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.

RachaelBrown

2014-03-01

273

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

274

Cardiopulmonary baroreceptor control of muscle sympathetic nerve activity in heat-stressed humans  

Science.gov (United States)

Whole body heating decreases central venous pressure (CVP) while increasing muscle sympathetic nerve activity (MSNA). In normothermia, similar decreases in CVP elevate MSNA, presumably via cardiopulmonary baroreceptor unloading. The purpose of this project was to identify whether increases in MSNA during whole body heating could be attributed to cardiopulmonary baroreceptor unloading coincident with the thermal challenge. Seven subjects were exposed to whole body heating while sublingual temperature, skin blood flow, heart rate, arterial blood pressure, and MSNA were monitored. During the heat stress, 15 ml/kg warmed saline was infused intravenously over 7-10 min to increase CVP and load the cardiopulmonary baroreceptors. We reported previously that this amount of saline was sufficient to return CVP to pre-heat stress levels. Whole body heating increased MSNA from 25 +/- 3 to 39 +/- 3 bursts/min (P bursts/min, P > 0.05 relative to heat stress period) and did not alter mean arterial blood pressure (MAP) or pulse pressure. To identify whether arterial baroreceptor loading decreases MSNA during heat stress, in a separate protocol MAP was elevated via steady-state infusion of phenylephrine during whole body heating. Increasing MAP from 82 +/- 3 to 93 +/- 4 mmHg (P bursts/min (P < 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating is not the primary mechanism resulting in elevations in MSNA. Moreover, arterial baroreceptors remain capable of modulating MSNA during heat stress.

Crandall, C. G.; Etzel, R. A.; Farr, D. B.

1999-01-01

275

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

Directory of Open Access Journals (Sweden)

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.

A. M. Durigon

2005-03-01

276

Role of the endogenous opioid system in modulation of urinary bladder activity by spinal nerve stimulation.  

Science.gov (United States)

The role of the endogenous opioid system in modulation of urinary bladder activity by spinal nerve (SN) stimulation was studied in anesthetized female rats, using the rat model of isovolumetric bladder contraction. SN stimulation at a fixed frequency of 10 Hz attenuated bladder contraction frequency; the magnitude of the inhibition was directly proportional to the current intensity. Neither the ?-opioid antagonist nor-binaltorphimine (2 mg/kg iv) nor the ?-opioid antagonist naltrindole (5 mg/kg iv) attenuated the bladder inhibitory response to SN stimulation. In contrast, the ?-opioid receptor antagonist naloxone (NLX; 0.03 mg/kg iv) blocked the inhibitory responses evoked by SN stimulation at therapeutic current intensities at ?1 × motor threshold current (Tmot). An action at spinal and supraspinal centers was further confirmed by the ability of intrathecal or intracerebroventricular administration of NLX methiodide to attenuate the bladder inhibitory effects of 1 × Tmot SN stimulation. The magnitude of SN-mediated neuromodulation using therapeutically relevant stimulation intensity (Tmot) is equivalent to 0.16 mg/kg of systemically administered morphine, which produces 50% inhibition of bladder contraction frequency. These results suggest that the inhibitory effects of lower intensity SN stimulation may be mediated through the release of endogenous ?-opioid peptides. Additionally, these data suggest that neuromodulation may offer a mode of treating the symptoms of overactive bladder with efficacy equal to the opioid drugs but without their liability for abuse and dependence. PMID:23637207

Su, Xin; Nickles, Angela; Nelson, Dwight E

2013-07-01

277

Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-?-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton's Jelly: In Vitro and In Vivo Analysis  

OpenAIRE

In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton's jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-?-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Results in vitro s...

Pereira, T.; Ga?rtner, A.; Amorim, I.; Almeida, A.; Caseiro, A. R.; Armada-da-silva, Paulo A. S.; Amado, Sandra; Fregnan, Federica; Vareja?o, A. S. P.; Santos, J. D.; Bartolo, P. J.; Geuna, S.; Lui?s, A. L.; Mauricio, A. C.

2014-01-01

278

Atrial granular cells of the snail Achatina fulica release proteins into hemolymph after stimulation of the heart nerve.  

Science.gov (United States)

The atrium of the gastropod mollusc Achatina fulica receives rich innervation and contains numerous granular cells (GCs). We studied the atrial innervation and discovered that axon profiles typical in appearance of peptidergic neurons form close unspecialized membrane contacts with GCs. Then, we investigated, at both morphological and biochemical levels, the effect of electrical stimulation of the heart nerve on GCs of Achatina heart perfused in situ. The ultrastructural study demonstrated changes in granule morphology consistent with secretion. These events included alteration of granule content, intracellular granule fusion and formation of complex degranulation channels, within which the granule matrix solubilized. It was shown that electrical stimulation resulted in a significant increase of the total protein concentration in the perfusate. Furthermore, SDS-PAGE analysis of the perfusate revealed three new proteins with molecular masses of 16, 22, and 57 kDa. Affinity-purified polyclonal antibodies against the 16 kDa protein were obtained; the whole-mount immunofluorescence technique revealed the presence of this protein in the granules of atrial GCs. In GCs of the stimulated atrium, a progressive loss of their granular content was observed. The results suggest that the central nervous system can modulate the secretory activity of the atrial GCs through non-synaptic pathways. PMID:19801425

Shabelnikov, Sergej V; Bystrova, Olga A; Ivanov, Vadim A; Margulis, Boris A; Martynova, Marina

2009-10-01

279

Cutaneous nerve transection for the management of intractable upper extremity pain caused by invasive squamous cell carcinoma.  

Science.gov (United States)

A recurrent clinical dilemma in the management of patients with painful metastatic lesions is achieving a balance between effective analgesic therapies versus intolerable side effects, in particular altered mental status. We present the case of an immunosuppressed patient post-lung transplant who was suffering from intractable pain caused by widely metastatic squamous cell carcinoma. The patient's progressive, excruciating neuropathic pain was localized to the area of the left wrist and forearm. Additionally, the patient complained of moderate pain at sites of tumor involvement on her right arm and scalp. Attempts to adequately manage her left upper extremity pain included a combination of pharmacologic treatments intended to treat neuropathic pain (gabapentin, SNRI, ketamine, opioids) and focused regional analgesia (infraclavicular infusion of local anesthetic). However, the patient developed intolerable side effects including altered mental status and delirium associated with the systemic agents and suboptimal control with the infraclavicular infusion. Given that the most severe pain was well localized, we undertook a diagnostic block of the cutaneous nerves of the left forearm. As this intervention significantly reduced her pain, we subsequently performed neurectomies to the left superficial radial nerve, lateral cutaneous nerve of the forearm and the posterior cutaneous nerve of the forearm. This resulted in immediate and continued relief of her left upper extremity pain without an altered mental status. Residual focal pain from lesions over her right arm and scalp was successfully managed with daily topical applications of lidocaine and capsaicin cream. Successful pain control continued until the patient's death five months later. PMID:21306862

Turnbull, John H; Gebauer, Sara L; Miller, Bruce L; Barbaro, Nicholas M; Blanc, Paul D; Schumacher, Mark A

2011-07-01

280

Fibroblast growth factor-2 gene delivery stimulates axon growth by adult retinal ganglion cells after acute optic nerve injury.  

Science.gov (United States)

Basic fibroblast growth factor (or FGF-2) has been shown to be a potent stimulator of retinal ganglion cell (RGC) axonal growth during development. Here we investigated if FGF-2 upregulation in adult RGCs promoted axon regrowth in vivo after acute optic nerve injury. Recombinant adeno-associated virus (AAV) was used to deliver the FGF-2 gene to adult RGCs providing a sustained source of this neurotrophic factor. FGF-2 gene transfer led to a 10-fold increase in the number of axons that extended past 0.5 mm from the lesion site compared to control nerves. Detection of AAV-mediated FGF-2 protein in injured RGC axons correlated with growth into the distal optic nerve. The response to FGF-2 upregulation was supported by our finding that FGF receptor-1 (FGFR-1) and heparan sulfate (HS), known to be essential for FGF-2 signaling, were expressed by adult rat RGCs. FGF-2 transgene expression led to only transient protection of injured RGCs. Thus the effect of this neurotrophic factor on axon extension could not be solely attributed to an increase in neuronal survival. Our data indicate that selective upregulation of FGF-2 in adult RGCs stimulates axon regrowth within the optic nerve, an environment that is highly inhibitory for regeneration. These results support the hypothesis that key factors involved in axon outgrowth during neural development may promote regeneration of adult injured neurons. PMID:14664816

Sapieha, Przemyslaw S; Peltier, Martin; Rendahl, Katherine G; Manning, William C; Di Polo, Adriana

2003-11-01

281

Effects of collagen membranes enriched with in vitro-differentiated N1E-115 cells on rat sciatic nerve regeneration after end-to-end repair  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group, end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group; and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group. Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT, withdrawal reflex latency (WRL and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat.

Fornaro Michele

2010-02-01

282

Gonadotrophin-releasing hormone nerve terminals, tanycytes and neurohaemal junction remodelling in the adult median eminence: functional consequences for reproduction and dynamic role of vascular endothelial cells.  

Science.gov (United States)

Although coordinated actions of several areas within the hypothalamus are involved in the secretion of gonadotrophin-releasing hormone (GnRH), the median eminence of the hypothalamus, where the nerve terminals are located, plays a particularly critical role in the release of GnRH. In adult females, prior to the preovulatory surge of GnRH, the retraction of specialised ependymoglial cells lining the floor of the third ventricle named tanycytes allows for the juxtaposition of GnRH nerve terminals with the adjacent pericapillary space of the pituitary portal vasculature, thus forming direct neurohaemal junctions. These morphological changes occur within a few hours and are reversible. Such remodelling may promote physiological conditions to enhance the central release of GnRH and potentiate oestrogen-activated GnRH release. This plasticity involves dynamic cell interactions that bring into play tanycytes, astrocytes, vascular endothelial cells and GnRH neurones themselves. The underlying signalling pathways responsible for these structural changes are comprised of highly diffusible gaseous molecules, such as endothelial nitric oxide, and paracrine communication processes involving receptors of the erbB tyrosine kinase family, transforming growth factor beta 1 and eicosanoids, such as prostaglandin E(2). Some of these molecules, as a result of their ability to diffuse within the median eminence, may also serve as synchronizing cues allowing for the occurrence of functionally meaningful episodes of GnRH secretion by coordinating GnRH release from the GnRH neuroendocrine terminals. PMID:20492366

Prevot, V; Bellefontaine, N; Baroncini, M; Sharif, A; Hanchate, N K; Parkash, J; Campagne, C; de Seranno, S

2010-07-01

283

Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat.  

Science.gov (United States)

Citicoline and lithium (Li(-)) have been shown to support retinal ganglion cell (RGC) survival and axon regeneration in vitro. Optic nerve crush (ONC) is a model of both brain axonal injury and certain aspects of the glaucomatous degeneration of RGC. We have used this model to quantify protection offered to RGC by these drugs and to determine whether their effects are mediated by enhanced expression of the antiapoptotic protein Bcl-2. Adult rats (6-12 per group) were subjected to ONC accompanied by a contralateral sham operation. Animals were treated intraperitoneally with either vehicle, citicoline sodium (1g/kg daily for up to 7 days and 300 mg/kg daily afterwards), lithium chloride (30 mg/kg daily), or both drugs combined. Fluorogold was injected bilaterally into superior colliculi 1, 5 or 19 days after ONC. Labeled cells were counted under a fluorescence microscope 2 days after tracer injection. In a separate set of experiments the effects of treatments on expression of Bcl-2 in retinas were evaluated by immunohistochemistry. In vehicle-treated animals there was a progressive decrease of RGC density after crush. This decrease was attenuated in citicoline-treated animals 1 week and 3 weeks after the crush. In the lithium-treated group protection was even more pronounced. In animals treated with both drugs RGC protection was similar to that achieved by lithium alone. Bcl-2 immunoreactivity was seen predominantly in retinal ganglion cells. Its increase was recorded in the lithium and citicoline group as well as in animals treated with the combination of both drugs. Both citicoline and lithium protect RGC and their axons in vivo against delayed degeneration triggered by the ONC. Retinoprotective action of both drugs may involve an increase in Bcl-2 expression. PMID:16876158

Schuettauf, Frank; Rejdak, Robert; Thaler, Sebastian; Bolz, Sylvia; Lehaci, Cristiana; Mankowska, Anna; Zarnowski, Tomasz; Junemann, Anselm; Zagorski, Zbigniew; Zrenner, Eberhart; Grieb, Pawel

2006-11-01

284

Neuroglial ATP release through innexin channels controls microglial cell movement to a nerve injury  

OpenAIRE

Microglia, the immune cells of the central nervous system, are attracted to sites of injury. The injury releases adenosine triphosphate (ATP) into the extracellular space, activating the microglia, but the full mechanism of release is not known. In glial cells, a family of physiologically regulated unpaired gap junction channels called innexons (invertebrates) or pannexons (vertebrates) located in the cell membrane is permeable to ATP. Innexons, but not pannexons, also pair to make gap juncti...

Samuels, Stuart E.; Lipitz, Jeffrey B.; Dahl, Gerhard; Muller, Kenneth J.

2010-01-01

285

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

OpenAIRE

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 ...

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

2012-01-01

286

Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days; Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.

Pan Hung-Chuan

2009-08-01

287

Evaluation of peripapillary retinal nerve fiber layer, macula and ganglion cell thickness in amblyopia using spectral optical coherence tomography  

OpenAIRE

AIM:To investigate peripapillary retinal nerve fiber layer (RNFL), macula and ganglion cell layer thicknesses (GCC) in amblyopic eyes with spectral domain optical coherence tomography (SD-OCT).METHODS:Thirty six patients with a history of unilateral amblyopia and thirty two children who had emmetropia without amblyopia were included in this study.In this institutional study, 36 eyes of 36 patients with amblyopia (AE), 36 fellow eyes without amblyopia (FE), and 32 eyes of 32 norm...

Penpe Gul Firat

2013-01-01

288

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

OpenAIRE

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-responsiv...

Dwaipayan Sen; Michael Huchital; Chen, Yulong L.

2013-01-01

289

Age and facial nerve axotomy-induced T cell trafficking: Relation to microglial and motor neuron status  

OpenAIRE

Following peripheral axotomy of the facial nerve in mice, T lymphocytes cross the blood-brain-barrier (BBB) into the central nervous system (CNS), where they home to neuronal cell bodies of origin in the facial motor nucleus (FMN) and act in concert with microglial cells to support the injured motor neurons. Several lines of evidence suggested normal aging may alter the injury-related responses of T cells, microglia, and motor neurons in this model. In this study, we therefore sought to test ...

Dauer, Daniel J.; Huang, Zhi; Ha, Grace K.; Kim, Jeremy; Khosrowzadeh, David; Petitto, John M.

2011-01-01

290

Nerve growth factor (NGF) induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA.  

OpenAIRE

Human nerve growth factor (NGF) receptor (NGFR) cDNA was transfected into a neuroblastoma cell line (HTLA 230) which does not express a functional NGF-NGFR signal transduction cascade. Short-term treatment of stably transfected cells (98-3) expressing membrane-bound NGF receptor molecules resulted in a cell cycle-dependent, transient expression of the c-fos gene upon treatment with NGF, suggesting the presence of functional high-affinity NGFR. Extensive outgrowth of neurites and cessation of ...

Matsushima, H.; Bogenmann, E.

1990-01-01

291

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

292

Toxicogenomic studies of human neural cells following exposure to organophosphorus chemical warfare nerve agent VX.  

Science.gov (United States)

Organophosphorus (OP) compounds represent an important group of chemical warfare nerve agents that remains a significant and constant military and civilian threat. OP compounds are considered acting primarily via cholinergic pathways by binding irreversibly to acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Many studies over the past years have suggested that other mechanisms of OP toxicity exist, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. Here we performed a microarray study in which cultured human neural cells were exposed to 0.1 or 10 ?M of VX for 1 h. Global gene expression changes were analyzed 6, 24, and 72 h post exposure. Functional annotation and pathway analysis of the differentially expressed genes has revealed many genes, networks and canonical pathways that are related to nervous system development and function, or to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In particular, the neuregulin pathway impacted by VX exposure has important implications in many nervous system diseases including schizophrenia. These results provide useful information valuable in developing suitable antidotes for more effective prevention and treatment of, as well as in developing biomarkers for, VX-induced chronic neurotoxicity. PMID:23440544

Gao, Xiugong; Lin, Hsiuling; Ray, Radharaman; Ray, Prabhati

2013-05-01

293

Hepatic nerve growth factor induced by iron overload triggers defenestration in liver sinusoidal endothelial cells.  

Science.gov (United States)

The fenestrations of liver sinusoidal endothelial cells (LSECs) play important roles in the exchange of macromolecules, solutes, and fluid between blood and surrounding liver tissues in response to hepatotoxic drugs, toxins, and oxidative stress. As excess iron is a hepatotoxin, LSECs may be affected by excess iron. In this study, we found a novel link between LSEC defenestration and hepatic nerve growth factor (NGF) in iron-overloaded mice. By Western blotting, NGF was highly expressed, whereas VEGF and HGF were not, and hepatic NGF mRNA levels were increased according to digital PCR. Immunohistochemically, NGF staining was localized in hepatocytes, while TrkA, an NGF receptor, was localized in LSECs. Scanning electron microscopy revealed LSEC defenestration in mice overloaded with iron as well as mice treated with recombinant NGF. Treatment with conditioned medium from iron-overloaded primary hepatocytes reduced primary LSEC fenestrations, while treatment with an anti-NGF neutralizing antibody or TrkA inhibitor, K252a, reversed this effect. However, iron-loaded medium itself did not reduce fenestration. In conclusion, iron accumulation induces NGF expression in hepatocytes, which in turn leads to LSEC defenestration via TrkA. This novel link between iron and NGF may aid our understanding of the development of chronic liver disease. PMID:25460199

Addo, Lynda; Tanaka, Hiroki; Yamamoto, Masayo; Toki, Yasumichi; Ito, Satoshi; Ikuta, Katsuya; Sasaki, Katsunori; Ohtake, Takaaki; Torimoto, Yoshihiro; Fujiya, Mikihiro; Kohgo, Yutaka

2015-01-01

294

[A new method of anastomosing severed nerves].  

Science.gov (United States)

Nerve anastomoses glued with "Fribrinkleber" can be protected from tissue plasminogen-activators both by natural and synthetic inhibitors of fibrinolysis whether administered locally or systemically. The glued nerve-anastomoses do not attain the bond strength of sutured nerves, but show less foreign body reaction. Gluing nerves with Fibrinkleber" combined with inhibition of fibrinolysis would seem to be a good method for reuniting severed nerves. It may be especially useful in nerve transplantation if tension is avoided. PMID:376235

Duspiva, W; Blümel, G; Haas-Denk, S; Wriedt-Lübbe, I

1977-04-01

295

Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse.  

Science.gov (United States)

Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS). In the present study, we used heterozygous Cx3cr1GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN) ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), primary and secondary somatosensory cortex (S1 and S2), insular cortex (IC), amygdala, hippocampus, periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons. PMID:18423014

Zhang, Fuxing; Vadakkan, Kujumon I; Kim, Susan S; Wu, Long-Jun; Shang, Yuze; Zhuo, Min

2008-01-01

296

Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS. In the present study, we used heterozygous Cx3cr1GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC, prefrontal cortex (PFC, primary and secondary somatosensory cortex (S1 and S2, insular cortex (IC, amygdala, hippocampus, periaqueductal gray (PAG and rostral ventromedial medulla (RVM. Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons.

Shang Yuze

2008-04-01

297

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

Directory of Open Access Journals (Sweden)

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.

RachaelBrown

2012-10-01

298

Nerve growth factor-dependent survival of CESS B cell line is mediated by increased expression and decreased degradation of MAPK phosphatase 1.  

Science.gov (United States)

The sIgG(+) lymphoblastoid B cell line CESS spontaneously produces a high amount of nerve growth factor (NGF) and expresses both high affinity (p140(Trk-A)) and low affinity (p75(NTR)) NGF receptors. Autocrine production of NGF maintains the survival of CESS cells through the continuous deactivation of p38 MAPK, an enzyme able to induce Bcl-2 phosphorylation and subsequent cytochrome c release and caspase activation. In this paper, we show that NGF induces transcriptional activation and synthesis of MAPK phosphatase 1 (MKP-1), a dual specificity phosphatase that dephosphorylates p38 MAPK, thus preventing Bcl-2 phosphorylation. Furthermore, NGF increases MKP-1 protein stability by preventing its degradation through the proteasome pathway. Following NGF stimulation, MKP-1 protein mainly localizes on mitochondria, suggesting an interaction with p38 MAPK in this compartment. Incubation of CESS cells with MKP-1-specific antisense oligonucleotides induces cell death, which was not prevented by exogenous NGF. By contrast, overexpression of native MKP-1, but not of its catalytically impaired form, inhibits apoptosis induced by NGF neutralization in CESS cells. Thus, the molecular mechanisms underlying the survival function of NGF in CESS B cell line predominantly consist in maintaining elevated levels of MKP-1 protein, which controls p38 MAPK activation. PMID:14724291

Rosini, Paolo; De Chiara, Giovanna; Bonini, Paolo; Lucibello, Maria; Marcocci, Maria Elena; Garaci, Enrico; Cozzolino, Federico; Torcia, Maria

2004-04-01

299

Arterial baroreflex control of muscle sympathetic nerve activity under orthostatic stress in humans  

Directory of Open Access Journals (Sweden)

Full Text Available The mechanisms by which blood pressure is maintained against the orthostatic stress caused by gravity’s effect on the fluid distribution within the body are important issues in physiology, especially in humans who usually adopt an upright posture. Peripheral vasoconstriction and increased heart rate are major cardiovascular adjustments to orthostatic stress and comprise part of the reflex response elicited via the carotid sinus and aortic baroreceptors (arterial baroreflex: ABR and cardiopulmonary stretch receptors (cardiopulmonary baroreflex. In a series of studies, we have been characterizing the ABR-mediated regulation of cardiovascular hemodynamics and muscle sympathetic nerve activity (MSNA while applying orthostatic stress in humans. We have found that under orthostatic stress, dynamic carotid baroreflex responses are modulated as exemplified by the increases in the MSNA, blood pressure and heart rate responses elicited by carotid baroreflex unloading and the shorter period of MSNA suppression, comparable reduction and faster recovery of MAP and greater heart rate response to carotid baroreflex stimulation. Our results also show that ABR-mediated beat-to-beat control over burst incidence, burst strength and total MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that the sensitivity of ABR control over the aforementioned MSNA variables is substantially reduced during the development of syncope. We suggest that in humans, the modulation of ABR function under orthostatic stress may be one of the mechanisms by which blood pressure is maintained and orthostatic hypotension limited, and impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope.

MasashiIchinose

2012-08-01

300

Increased sympathetic nerve activity correlates with neurovascular compression at the rostral ventrolateral medulla.  

Science.gov (United States)

We used microneurography to measure muscle sympathetic nerve activity (MSNA) in 25 hypertensive subjects and correlated these results with the presence or absence of signs of neurovascular compression (NVC) at the rostral ventrolateral (RVL) medulla on MRI. Subjects were divided into 3 groups based on MRI findings: NVC-, no MRI evidence of NVC (N=9); NVC+contact, image showing artery in contact but not compressing the RVL medulla (N=8); and NVC+compression, image showing arterial compression of the RVL medulla (N=8). The MSNA measurements were performed at rest, after a hypothermic stimulus, and during isometric exercise. The MSNA during rest in the NVC+compression group was significantly higher than that in the NVC+contact and NVC- groups (30.4+/-3.4 versus 17.5+/-1.1 and 21.4+/-3.2 spikes per minute, respectively). However, the blood pressure in the NVC+compression group was slightly but not significantly higher than that in the other 2 groups (183+/-7/115+/-8, 174+/-6/108+/-7, and 171+/-5/110+/-5 mm Hg, respectively). The increases in MSNA, blood pressure, and heart rate during the cold pressor and isometric exercise tests were similar. Our results show that, although resting MSNA is elevated in patients with true NVC of the RVL medulla, patients without NVC or with arterial contact but not overt compression of the RVL medulla have similar MSNA. These findings are important for identifying, among hypertensive patients with NVC, individuals who may have associated physiological repercussions, such as increased sympathetic activity. PMID:16567595

Sendeski, Mauricio M; Consolim-Colombo, Fernanda Marciano; Leite, Claudia Costa; Rubira, Marcelo Custódio; Lessa, Patricia; Krieger, Eduardo Moacyr

2006-05-01

301

Arterial baroreflex control of muscle sympathetic nerve activity under orthostatic stress in humans.  

Science.gov (United States)

The mechanisms by which blood pressure is maintained against the orthostatic stress caused by gravity's effect on the fluid distribution within the body are important issues in physiology, especially in humans who usually adopt an upright posture. Peripheral vasoconstriction and increased heart rate (HR) are major cardiovascular adjustments to orthostatic stress and comprise part of the reflex response elicited via the carotid sinus and aortic baroreceptors (arterial baroreflex: ABR) and cardiopulmonary stretch receptors (cardiopulmonary baroreflex). In a series of studies, we have been characterizing the ABR-mediated regulation of cardiovascular hemodynamics and muscle sympathetic nerve activity (MSNA) while applying orthostatic stress in humans. We have found that under orthostatic stress, dynamic carotid baroreflex responses are modulated as exemplified by the increases in the MSNA, blood pressure, and HR responses elicited by carotid baroreflex unloading and the shorter period of MSNA suppression, comparable reduction and faster recovery of mean arterial blood pressure (MAP) and greater HR response to carotid baroreflex stimulation. Our results also show that ABR-mediated beat-to-beat control over burst incidence, burst strength and total MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that the sensitivity of ABR control over the aforementioned MSNA variables is substantially reduced during the development of syncope. We suggest that in humans, the modulation of ABR function under orthostatic stress may be one of the mechanisms by which blood pressure is maintained and orthostatic hypotension limited, and impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope. PMID:22934064

Ichinose, Masashi; Nishiyasu, Takeshi

2012-01-01

302

Relationships between auditory nerve activity and temporal pitch perception in cochlear implant users.  

Science.gov (United States)

Cochlear implant (CI) users can derive a musical pitch from the temporal pattern of pulses delivered to one electrode. However, pitch perception deteriorates with increasing pulse rate, and most listeners cannot detect increases in pulse rate beyond about 300 pps. In addition, previous studies using irregular pulse trains suggest that pitch can be substantially influenced by neural refractory effects. We presented electric pulse trains to one CI electrode and measured rate discrimination, pitch perception, and auditory nerve (AN) activity in the same subjects and with the same stimuli. The measures of AN activity, obtained using the electrically evoked compound action potential (ECAP), replicated the well-known finding that the neural response to isochronous pulse trains at rates above about 200-300 pps is modulated, with the ECAP being larger to odd-numbered than to even-numbered pulses. This finding has been attributed to refractoriness. Behavioural results replicated the deterioration in rate discrimination at rates above 200-300 pps and the finding that pulse trains whose inter-pulse intervals (IPIs) alternate between a shorter and a longer value (e.g. 4 and 6 ms) have a pitch lower than that corresponding to the mean IPI. To link ECAP modulation to pitch, we physically modulated a 200-pps pulse train by attenuating every other pulse and measured both ECAPs and pitch as a function of modulation depth. Our results show that important aspects of temporal pitch perception cannot be explained in terms of the AN response, at least as measured by ECAPs, and suggest that pitch is influenced by refractory effects occurring central to the AN. PMID:23716242

Carlyon, Robert P; Deeks, John M

2013-01-01

303

Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation.  

Science.gov (United States)

Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 ?g/ml, 10 ?l) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow A?-fibers (2-7 m/s) than fast A?-fibers (7-12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner. PMID:25122708

Wong, Hayes; Dong, Xu-Dong; Cairns, Brian E

2014-11-01

304

Spontaneous activity of auditory nerve fibers in the barn owl (Tyto alba): analyses of interspike interval distributions.  

Science.gov (United States)

In vertebrate auditory systems, the conversion from graded receptor potentials across the hair-cell membrane into stochastic spike trains of the auditory nerve (AN) fibers is performed by ribbon synapses. The statistics underlying this process constrain auditory coding but are not precisely known. Here, we examine the distributions of interspike intervals (ISIs) from spontaneous activity of AN fibers of the barn owl (Tyto alba), a nocturnal avian predator whose auditory system is specialized for precise temporal coding. The spontaneous activity of AN fibers, with the exception of those showing preferred intervals, is commonly thought to result from excitatory events generated by a homogeneous Poisson point process, which lead to spikes unless the fiber is refractory. We show that the ISI distributions in the owl are better explained as resulting from the action of a brief refractory period ( approximately 0.5 ms) on excitatory events generated by a homogeneous stochastic process where the distribution of interevent intervals is a mixture of an exponential and a gamma distribution with shape factor 2, both with the same scaling parameter. The same model was previously shown to apply to AN fibers in the cat. However, the mean proportions of exponentially versus gamma-distributed intervals in the mixture were different for cat and owl. Furthermore, those proportions were constant across fibers in the cat, whereas they covaried with mean spontaneous rate and with characteristic frequency in the owl. We hypothesize that in birds, unlike in mammals, more than one ribbon may provide excitation to most fibers, accounting for the different proportions, and that variation in the number of ribbons may underlie the variation in the proportions. PMID:19357334

Neubauer, Heinrich; Köppl, Christine; Heil, Peter

2009-06-01

305

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Public Health | Language: English Abstract in english 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.

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

2009-12-01

306

Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease  

OpenAIRE

BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in pati...

Bassotti, G.; Battaglia, E.; Bellone, G.; Dughera, L.; Fisogni, S.; Zambelli, C.; Morelli, A.; Mioli, P.; Emanuelli, G.; Villanacci, V.

2005-01-01

307

Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease  

Science.gov (United States)

Background: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. Aims: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. Patients: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. Methods: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. Results: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p ?=? 0.103 and p ?=? 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p ?=? 0.0003) reduced compared with controls, as were glial cells (p ?=? 0.0041). Conclusions: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition. PMID:16126881

Bassotti, G; Battaglia, E; Bellone, G; Dughera, L; Fisogni, S; Zambelli, C; Morelli, A; Mioli, P; Emanuelli, G; Villanacci, V

2005-01-01

308

Sensory nerves and pancreatitis.  

Science.gov (United States)

Sensory nerves are a kind of nerve that conduct afferent impulses from the periphery receptors to the central nervous system (CNS) and are able to release neuromediators from the activated peripheral endings. Sensory nerves are particularly important for microcirculatory response, and stimulation of pancreatic sensory nerves releases a variety of neuropeptides such as substance P (SP), calcitonin gene-related peptide (CGRP), etc., leading to neurogenic inflammation characterized as the local vasodilatation and plasma extravasation. Deactivation of sensory nerves often leads to the disturbances of pancreatic microcirculation. Pancreatitis is a common digestive disease that can lead to severe complications and even death if it goes untreated. Experimental studies in animals and tissue analysis in patients with pancreatitis have shown significant changes in sensory nerves supplying the pancreatic gland. Thus making clear the whole mechanism of pancreatitis is essential to treat and cure it. Sensory nerves may have a close correlation with the development of pancreatitis, and knowing more about the role of sensory nerve in pancreatitis is important for the treatment for pancreatitis. This review is aimed to summarize the relationship between sensory nerves and pancreatitis. PMID:25493260

Li, Qingfu; Peng, Jie

2014-11-01

309

Sustained effect of bone marrow mononuclear cell therapy in axonal regeneration in a model of optic nerve crush.  

Science.gov (United States)

In adult mammals, the regeneration of the optic nerve is very limited and at the moment there are several groups trying different approaches to increase retinal ganglion cell (RGC) survival and axonal outgrowth. One promising approach is cell therapy. In previous work, we performed intravitreal transplantation of bone-marrow mononuclear cells (BMMCs) after optic nerve crush in adult rats and we demonstrated an increase in RGC survival and axon outgrowth 14 days after injury. In the present work, we investigated if these results could be sustained for a longer period of time. Optic nerve crush was performed in Lister-hooded adult rats and BMMC or saline injections were performed shortly after injury. Neuronal survival and regeneration were evaluated in rats? retina and optic nerve after 28 days. We demonstrated an increase of 5.2 fold in the axon outgrowth 28 days after lesion, but the BMMCs had no effect on RGC survival. In an attempt to prolong RGC survival, we established a new protocol with two BMMC injections, the second one 7 days after the injury. Untreated animals received two injections of saline. We observed that although the axonal outgrowth was still increased after the second BMMC injection, the RGC survival was not significantly different from untreated animals. These results demonstrate that BMMCs transplantation promotes neuroregeneration at least until 28 days after injury. However, the effects on RGC survival previously observed by us at 14 days were not sustained at 28 days and could not be prolonged with a second dose of BMMC. PMID:25204691

Zaverucha-do-Valle, Camila; Mesentier-Louro, Louise; Gubert, Fernanda; Mortari, Nicoli; Padilha, Ana Beatriz; D Paredes, Bruno; Mencalha, Andre; Abdelhay, Eliana; Teixeira, Camila; G M Ferreira, Fernanda; Tovar-Moll, Fernanda; Lopes de Souza, Sergio Augusto; Gutfilen, Bianca; Mendez-Otero, Rosalia; F Santiago, Marcelo

2014-10-31

310

Chitosan/silk fibroin-based, Schwann cell-derived extracellular matrix-modified scaffolds for bridging rat sciatic nerve gaps.  

Science.gov (United States)

Extracellular matrix (ECM) plays a prominent role in establishing and maintaining an ideal microenvironment for tissue regeneration, and ECM scaffolds are used as a feasible alternative to cellular and molecular therapy in the fields of tissue engineering. Because of their advantages over tissue-derived ECM scaffolds, cultured cell-derived ECM scaffolds are beginning to attract attention, but they have been scarcely studied for peripheral nerve repair. Here we aimed to develop a tissue engineered nerve scaffold by reconstituting nerve cell-derived ECM with natural biomaterials. A protocol was adopted to prepare and characterize the cultured Schwann cell (SC)-derived ECM. A chitosan conduit and silk fibroin (SF) fibers were prepared, cultured with SCs for ECM deposition, and subjected to decellularization, followed by assembly into a chitosan/SF-based, SC-derived ECM-modified scaffold, which was used to bridge a 10 mm rat sciatic nerve gap. The results from morphological analysis as well as electrophysiological examination indicated that regenerative outcomes achieved by our developed scaffold were similar to those by an acellular nerve graft (namely a nerve tissue-derived ECM scaffold), but superior to those by a plain chitosan/SF scaffold. Moreover, blood and histopathological parameters confirmed the safety of scaffold modification by SC-derived ECM. Therefore, a hybrid scaffold based on joint use of acellular and classical biomaterials represents a promising approach to nerve tissue engineering. PMID:24360577

Gu, Yun; Zhu, Jianbin; Xue, Chengbin; Li, Zhenmeiyu; Ding, Fei; Yang, Yumin; Gu, Xiaosong

2014-02-01

311

Nerve Blocks  

Science.gov (United States)

... injection to achieve temporary pain relief. Often, such pain originates from the spine, but other areas commonly affected include the neck, buttocks, legs and arms. Delivering a nerve block injection allows a damaged nerve time to heal itself ...

312

Single Cell Ras-GTP Analysis Reveals Altered Ras Activity in a Subpopulation of Neurofibroma Schwann Cells but Not Fibroblasts*  

OpenAIRE

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by multiple neurofibromas, peripheral nerve tumors containing mainly Schwann cells and fibroblasts. The NF1 gene encodes neurofibromin, a tumor suppressor postulated to function in part as a Ras GTPase-activating protein. The roles of different cell types and of elevated Ras-GTP in neurofibroma formation are unclear. To determine which neurofibroma cell type has altered Ras-GTP regulation, we developed an immunocytochem...

Sherman, Larry S.; Atit, Radhika; Rosenbaum, Thorsten; Cox, Adrienne D.; Ratner, Nancy

2000-01-01

313

C6 glioma cell-conditioned medium induces neurite outgrowth and survival of rat chromaffin cells in vitro: comparison with the effects of nerve growth factor.  

OpenAIRE

The effects of medium conditioned by rat C6 glioma cells (C6-CM) on the survival, neurite formation, and catecholamine content of adrenal medullary cells in culture were investigated and compared with the effects of nerve growth factor (NGF). Adrenal medullary cells were isolated from 10-day-old rats and the proportions of surviving and neurite-extending cells were determined after 8 days in culture. In the presence of C6-CM virtually all seeded cells survived and 50% developed neuritic proce...

Unsicker, K.; Vey, J.; Hofmann, H. D.; Mu?ller, T. H.; Wilson, A. J.

1984-01-01

314

Implantation of neural stem cells embedded in hyaluronic acid and collagen composite conduit promotes regeneration in a rabbit facial nerve injury model  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract The implantation of neural stem cells (NSCs in artificial scaffolds for peripheral nerve injuries draws much attention. NSCs were ex-vivo expanded in hyaluronic acid (HA-collagen composite with neurotrophin-3, and BrdU-labeled NSCs conduit was implanted onto the ends of the transected facial nerve of rabbits. Electromyography demonstrated a progressive decrease of current threshold and increase of voltage amplitude in de-innervated rabbits after implantation for one, four, eight and 12 weeks compared to readouts derived from animals prior to nerve transection. The most remarkable improvement, observed using Electrophysiology, was of de-innervated rabbits implanted with NSCs conduit as opposed to de-innervated counterparts with and without the implantation of HA-collagen, NSCs and HA-collagen, and HA-collagen and neurotrophin-3. Histological examination displayed no nerve fiber in tissue sections of de-innervated rabbits. The arrangement and S-100 immunoreactivity of nerve fibers in the tissue sections of normal rabbits and injured rabbits after implantation of NSCs scaffold for 12 weeks were similar, whereas disorderly arranged minifascicles of various sizes were noted in the other three arms. BrdU+ cells were detected at 12 weeks post-implantation. Data suggested that NSCs embedded in HA-collagen biomaterial could facilitate re-innervations of damaged facial nerve and the artificial conduit of NSCs might offer a potential treatment modality to peripheral nerve injuries.

Sun Chong

2008-11-01

315

Aucubin Promotes Neurite Outgrowth in Neural Stem Cells and Axonal Regeneration in Sciatic Nerves  

OpenAIRE

Aucubin is an iridoid glycoside with a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities. Recently, it has been shown that aucubin prevents neuronal death in the hippocampal CA1 region in rats with diabetic encephalopathy. In addition, it has protective effects on H2O2-induced apoptosis in PC12 cells. We have shown here that aucubin promotes neuronal differentiation and neurite outgrowth in neural stem cells culture...

Kim, Yong Min; Sim, U-cheol; Shin, Yongsung; Kim Kwon, Yunhee

2014-01-01

316

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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.

A.L.R., Oliveira.

2001-03-01

317

Degenerative Nerve Diseases  

Science.gov (United States)

Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

318

Carbon nanotube-based electrochemical sensor for assay of salivary cholinesterase enzyme activity: an exposure biomarker of organophosphate pesticides and nerve agents.  

Science.gov (United States)

Certain saliva enzymes may be useful biomarkers for detecting exposures to organophosphate pesticides and chemical nerve agents. In this regard, saliva biomonitoring offers a simple and noninvasive approach for rapidly evaluating those exposures in real time. An electrochemical sensor coupled with a microflow injection system was developed for a simple, rapid, and sensitive characterization of cholinesterase (ChE) enzyme activities in rat saliva. The electrochemical sensor is based on a carbon nanotube (CNT)-modified screen-printed carbon electrode (SPE), which is integrated into a flow cell. Because of the excellent electrocatalytic activity of the CNTs, the sensor can detect electroactive species that are produced from enzymatic reactions with extremely high sensitivity and at low potentials. The electrochemical properties of acetylcholinesterase (AChE) enzymatic products were studied using a CNT-modified SPE, and the operation parameters such as the applied potential and substrate concentration were optimized to achieve the best performance. The AChE enzyme activity was further investigated using the CNT-based electrochemical sensor with commercially available purified AChE and ChE in saliva obtained from nave rats. It is found that the calibration curve is linear over a wide range of AChE concentrations from 5 pM to 0.5 nM, and the sensor is very sensitive with the detection limit down to 2 pM. The dynamics of the ChE enzyme activity in saliva with organophosphate pesticides was further studied using this sensor. The results showthatthe senor can be used to characterize salivary enzyme activity and to detect the exposure to organophosphate compounds. This new CNT-based electrochemical sensor thus provides a sensitive and quantitative tool for noninvasive biomonitoring of the exposure to organophosphate pesticides and nerve agents. PMID:18505017

Wang, Jun; Timchalk, Charles; Lin, Yuehe

2008-04-01

319

Evoked skin sympathetic nerve responses in man.  

OpenAIRE

Activity in human unmyelinated efferent nerve fibres was recorded from seven upper limb cutaneous nerve fascicles. The activity induced by contralateral nerve trunk stimulation or tone burst was averaged and could be compared providing the stimuli were delivered at random times and in a random sequence. The average evoked sympathetic nerve responses to nerve trunk stimulation and tone burst were identical in latency and duration.

Satchell, P. M.; Seers, C. P.

1987-01-01

320

Genetically encoded pH-indicators reveal activity-dependent cytosolic acidification of Drosophila motor nerve termini in vivo.  

Science.gov (United States)

All biochemical processes, including those underlying synaptic function and plasticity, are pH sensitive. Cytosolic pH (pH(cyto)) shifts are known to accompany nerve activity in situ, but technological limitations have prevented characterization of such shifts in vivo. Genetically encoded pH-indicators (GEpHIs) allow for tissue-specific in vivo measurement of pH. We expressed three different GEpHIs in the cytosol of Drosophila larval motor neurons and observed substantial presynaptic acidification in nerve termini during nerve stimulation in situ. SuperEcliptic pHluorin was the most useful GEpHI for studying pH(cyto) shifts in this model system. We determined the resting pH of the nerve terminal cytosol to be 7.30 ± 0.02, and observed a decrease of 0.16 ± 0.01 pH units when the axon was stimulated at 40 Hz for 4 s. Realkalinization occurred upon cessation of stimulation with a time course of 20.54 ± 1.05 s (?). The chemical pH-indicator 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein corroborated these changes in pH(cyto). Bicarbonate-derived buffering did not contribute to buffering of acid loads from short (? 4 s) trains of action potentials but did buffer slow (~60 s) acid loads. The magnitude of cytosolic acid transients correlated with cytosolic Ca(2+) increase upon stimulation, and partial inhibition of the plasma membrane Ca(2+)-ATPase, a Ca(2+)/H(+) exchanger, attenuated pH(cyto) shifts. Repeated stimulus trains mimicking motor patterns generated greater cytosolic acidification (~0.30 pH units). Imaging through the cuticle of intact larvae revealed spontaneous pH(cyto) shifts in presynaptic termini in vivo, similar to those seen in situ during fictive locomotion, indicating that presynaptic pH(cyto) shifts cannot be dismissed as artifacts of ex vivo preparations. PMID:23401611

Rossano, Adam J; Chouhan, Amit K; Macleod, Gregory T

2013-04-01

321

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

Science.gov (United States)

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

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

2010-01-15

322

Implantation of neural stem cells embedded in hyaluronic acid and collagen composite conduit promotes regeneration in a rabbit facial nerve injury model  

OpenAIRE

Abstract The implantation of neural stem cells (NSCs) in artificial scaffolds for peripheral nerve injuries draws much attention. NSCs were ex-vivo expanded in hyaluronic acid (HA)-collagen composite with neurotrophin-3, and BrdU-labeled NSCs conduit was implanted onto the ends of the transected facial nerve of rabbits. Electromyography demonstrated a progressive decrease of current threshold and increase of voltage amplitude in de-innervated rabbits after implantation for ...

Sun Chong; Tsang Kam; Wei Yue; Zhang Han; Li Jin; Huang Hua; Cui Fu; An Yi

2008-01-01

323

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

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...

Takaki, M.; Nakayama, S.

1991-01-01

324

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)

325

Nerve growth factor (NGF) induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA  

International Nuclear Information System (INIS)

Human nerve growth factor (NGF) receptor (NGFR) cDNA was transfected into a neuroblastoma cell line (HTLA 230) which does not express a functional NGF-NGFR signal transduction cascade. Short-term treatment of stably transfected cells (98-3) expressing membrane-bound NGF receptor molecules resulted in a cell cycle-dependent, transient expression of the c-fos gene upon treatment with NGF, suggesting the presence of functional high-affinity NGFR. Extensive outgrowth of neurites and cessation of DNA synthesis occurred in transfectants grown on an extracellular matrix after long-term treatment with NGF, suggesting terminal differentiation. Our data support the idea that introduction of a constitutively expressed NGFR cDNA into cells with neuronal background results in the assembly of a functional NGF-NGFR signal cascade in a permissive extracellular environment

326

Terminal nerve: cranial nerve zero  

Directory of Open Access Journals (Sweden)

Full Text Available It has been stated, in different types of texts, that there are only twelve pairs of cranial nerves. Such texts exclude the existence of another cranial pair, the terminal nerve or even cranial zero. This paper considers the mentioned nerve like a cranial pair, specifying both its connections and its functional role in the migration of liberating neurons of the gonadotropic hormone (Gn RH. In this paper is also stated the hypothesis of the phylogenetic existence of a cerebral sector and a common nerve that integrates the terminal nerve with the olfactory nerves and the vomeronasals nerves which seem to carry out the odors detection function as well as in the food search, pheromone detection and nasal vascular regulation.

Jorge Eduardo Duque Parra

2006-12-01

327

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

CERN Document Server

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

Shneider, M N

2014-01-01

328

Bladder Activation by Selective Stimulation of Pudendal Nerve Afferents in the Cat  

OpenAIRE

Bladder contractions evoked by pudendal nerve stimulation in both spinal intact and spinal transected cats support the possibility of restoring urinary function in persons with chronic spinal cord injury (SCI). However, electrically evoked bladder responses in persons with SCI were limited to transient contractions at relatively low pressures. This prompted the present study, which presents a detailed quantification of the responses evoked by selective stimulation of individual branches of th...

Yoo, Paul B.; Woock, John P.; Grill, Warren M.

2008-01-01

329

Identification of the prosurvival activity of nerve growth factor on cardiac myocytes  

OpenAIRE

Neurotrophins (NTs) control neuron survival and regeneration. Recent research showed that NTs possess cardiovascular actions. In this study, we investigated the hypothesis that the NT nerve growth factor (NGF) prevents cardiomyocyte apoptosis. We demonstrated that cultured rat neonatal cardiomyocytes (RNCMs) produce NGF and express its trkA (tropomyosin-related receptor A (NGF high-affinity receptor)) receptor. RNCMs given a neutralizing antibody for NGF or the trkA inhibitor K252a underwent ...

Caporali, A.; Sala-newby, Gb; Meloni, M.; Graiani, G.; Pani, E.; Cristofaro, B.; Newby, Ac; Madeddu, P.; Emanueli, C.

2008-01-01

330

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

OpenAIRE

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 inc...

Durigon, A. M.; Borja-oliveira, C. R.; Dal Belo, C. A.; Oshima-franco, Y.; Cogo, J. C.; Lapa, A. J.; Souccar, C.; Rodrigues-simioni, L.

2005-01-01

331

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

DEFF Research Database (Denmark)

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.

Jolivalt, CG; Fineman, M

2011-01-01

332

Nerve growth factor protects human keratinocytes from ultraviolet-B-induced apoptosis.  

Science.gov (United States)

Ultraviolet radiation is a potent inducer of apoptosis, whereas autocrine nerve growth factor protects human keratinocytes from programmed cell death. To evaluate the role of nerve growth factor in the mechanisms of ultraviolet B-induced apoptosis, cultured human keratinocytes were ultraviolet B irradiated following pretreatment with K252, a specific inhibitor of the tyrosine kinase high-affinity nerve growth factor receptor. Here we report that the addition of K252 significantly enhanced keratinocyte apoptosis. We then transfected normal human keratinocytes with pNUT-hNGF. Nerve growth factor overexpressing keratinocytes secreted the highest amounts of nerve growth factor in culture supernatants, were more viable, and had a higher rate of proliferation than mock-transfected cells. Whereas ultraviolet B radiation downregulated nerve growth factor mRNA and protein as well as the tyrosine kinase high-affinity nerve growth factor receptor in normal keratinocytes, it failed to do so in nerve growth factor-transfected cells. Moreover, nerve growth factor overexpressing keratinocytes were partially resistant to apoptosis induced by increasing doses of ultraviolet B at 24 and 48 h. These results indicate that downregulation of nerve growth factor function plays an important part in the mechanisms of ultraviolet B-induced apoptosis in human keratinocytes. In addition, ultraviolet B caused a decrease in BCL-2 and BCL-xL expression in mock-transfected keratinocytes, but not in nerve growth factor overexpressing cells. Finally, nerve growth factor prevented the cleavage of the enzyme poly(ADP-ribose) polymerase induced in human keratinocytes by ultraviolet B. These results are consistent with a model whereby the autocrine nerve growth factor protects human keratinocytes from ultraviolet B-induced apoptosis by maintaining constant levels of BCL-2 and BCL-xL, which in turn might block caspase activation. PMID:10594731

Marconi, A; Vaschieri, C; Zanoli, S; Giannetti, A; Pincelli, C

1999-12-01

333

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese 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.

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

2012-09-01

334

Pituitary Adenylate Cyclase-Activating Peptide and Vasoactive Intestinal Polypeptide Bias Langerhans Cell Ag Presentation Towards Th17 Cells  

OpenAIRE

Epidermal Langerhans cells (LCs) are dendritic APCs that play an important role in cutaneous immune responses. LCs are associated with epidermal nerves and the neuropeptides vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) inhibit LC Ag presentation for Th1-type immune responses. Here we examined whether PACAP or VIP modulates LC Ag presentation for induction of IL-17A-producing CD4+ T cells. Treatment with VIP or PACAP prior to in vitro L...

Din, Wanhong; Manni, Michela; Stohl, Lori L.; Zhou, Xi K.; Wagner, John A.; Granstein, Richard D.

2012-01-01

335

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

336

Induction of nerve growth factor by butanol fraction of Liriope platyphylla in C6 and primary astrocyte cells.  

Science.gov (United States)

Liriope platyphylla (LP) has been used as a tonic, antitussive, and expectorant in Korea for many years. In this study, we found that the buthanol fraction of Liriope platyphylla (BLP)-conditioned media of C6 and primary astrocyte induced the neurite outgrowth of PC12 cells, and that the effect was reversed by addition of nerve growth factor (NGF)-antibody and GF109203X, an inhibitor of protein kinase (PKC). Furthermore, we demonstrated that BLP increased the expression and secretion of NGF. GF109203X also decreased NGF expression in C6 cells. Taken together, our results suggest that astroglial NGF enhanced by BLP in a PKC-dependent pathway contributed to the induction of neurite outgrowth of PC12 cells. PMID:15305032

Hur, Jinyoung; Lee, Pyeongjae; Kim, Jeongmin; Kim, Ae Jung; Kim, Hocheol; Kim, Sun Yeou

2004-08-01

337

High sensitivity recording of afferent nerve activity using ultra-compliant microchannel electrodes: an acute in vivo validation  

Science.gov (United States)

Neuroprostheses interfaced with transected peripheral nerves are technological routes to control robotic limbs as well as convey sensory feedback to patients suffering from traumatic neural injuries or degenerative diseases. To maximize the wealth of data obtained in recordings, interfacing devices are required to have intrafascicular resolution and provide high signal-to-noise ratio (SNR) recordings. In this paper, we focus on a possible building block of a three-dimensional regenerative implant: a polydimethylsiloxane (PDMS) microchannel electrode capable of highly sensitive recordings in vivo. The PDMS 'micro-cuff' consists of a 3.5 mm long (100 µm × 70 µm cross section) microfluidic channel equipped with five evaporated Ti/Au/Ti electrodes of sub-100 nm thickness. Individual electrodes have average impedance of 640 ± 30 k? with a phase angle of -58 ± 1 degrees at 1 kHz and survive demanding mechanical handling such as twisting and bending. In proof-of-principle acute implantation experiments in rats, surgically teased afferent nerve strands from the L5 dorsal root were threaded through the microchannel. Tactile stimulation of the skin was reliably monitored with the three inner electrodes in the device, simultaneously recording signal amplitudes of up to 50 µV under saline immersion. The overall SNR was approximately 4. A small but consistent time lag between the signals arriving at the three electrodes was observed and yields a fibre conduction velocity of 30 m s-1. The fidelity of the recordings was verified by placing the same nerve strand in oil and recording activity with hook electrodes. Our results show that PDMS microchannel electrodes open a promising technological path to 3D regenerative interfaces.

Minev, Ivan R.; Chew, Daniel J.; Delivopoulos, Evangelos; Fawcett, James W.; Lacour, Stéphanie P.

2012-04-01

338

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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

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

339

Activation of glycogenolysis and norepinephrine overflow in the perfused rat liver during repetitive perivascular nerve stimulation.  

Science.gov (United States)

During in situ perfusion of rat liver stimulation of nerve bundles around hepatic artery and portal vein resulted in an increase of glucose output, a switch from lactate uptake to output and in a decrease of portal flow. These effects remained essentially the same during 3 stimulation periods at 20 min intervals; norepinephrine overflow, however, was strongly decreased during the second and third period. The metabolic and hemodynamic effects were not correlated to norepinephrine overflow during repetitive stimulations and during stimulations in the presence of norepinephrine, phentolamine, propranolol or desipramine. PMID:7152042

Beckh, K; Balks, H J; Jungermann, K

1982-11-29

340

Nerve supply to the pelvis (image)  

Science.gov (United States)

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal ... be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems ...

341

Effect of a centrally-acting muscle relaxant, eperisone hydrochloride, on muscle sympathetic nerve activity in humans.  

Science.gov (United States)

The sympatho-modulating effects of eperisone hydrochloride, a centrally acting muscle relaxant, on microneurographically recorded muscle sympathetic nerve activity (MSA) were analyzed in human volunteers. A single dose of 300 mg of eperisone was orally administered to 19 healthy subjects aged between 19 and 27, and effects on 1) spontaneous MSA in 30 degrees head-up tilted position, 2) resting MSA and responsiveness to standing, 3) exercise-induced enhancement of MSA were observed. Eperisone has a sympatho-suppressive action in resting skeletal muscles, but has no effect on MSA in actively contracting muscles, e.g. standing, hand-gripping. The sympatho-suppressive effect of eperisone may be related to the drug-induced increase of blood low in the resting skeletal muscles; also it may be one more mechanism through which the drug can exert its muscle relaxant action. PMID:1338431

Iwase, S; Mano, T; Saito, M; Ishida, G

1992-01-01

342

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

2009-11-15

343

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

DEFF Research Database (Denmark)

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

Mitchell, D.A.; Lambert, G.

2009-01-01

344

Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats.  

Science.gov (United States)

Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brain stem. Expiration is a passive process except for special metabolic conditions such as hypercapnia, when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase in CO(2) evokes late-expiratory (late-E) discharges phase-locked to phrenic bursts with the frequency increasing quantally as hypercapnia increases. In rats exposed to CIH, the late-E discharges synchronized in AbN and tSN emerge in normocapnia. To elucidate the possible neural mechanisms underlying these phenomena, we extended our computational model of the brain stem respiratory network by incorporating a population of presympathetic neurons in the rostral ventrolateral medulla that received inputs from the pons, medullary respiratory compartments, and retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Our simulations proposed that CIH conditioning increases the CO(2) sensitivity of RTN/pFRG neurons, causing a reduction in both the CO(2) threshold for emerging the late-E activity in AbN and tSN and the hypocapnic threshold for apnea. Using the in situ rat preparation, we have confirmed that CIH-conditioned rats under normal conditions exhibit synchronized late-E discharges in AbN and tSN similar to those observed in control rats during hypercapnia. Moreover, the hypocapnic threshold for apnea was significantly lowered in CIH-conditioned rats relative to that in control rats. We conclude that CIH may sensitize central chemoreception and that this significantly contributes to the neural impetus for generation of sympathetic activity and hypertension. PMID:21471394

Molkov, Yaroslav I; Zoccal, Daniel B; Moraes, Davi J A; Paton, Julian F R; Machado, Benedito H; Rybak, Ilya A

2011-06-01

345

Effects of anserine on the renal sympathetic nerve activity and blood pressure in urethane-anesthetized rats.  

Science.gov (United States)

Previous studies have demonstrated that central injection of L-carnosine (beta-alynyl-L-histidine), dipeptide synthesized in mammalian muscles, affects renal sympathetic nerve activity (RSNA) and blood pressure (BP) in anesthetized rats. In the present study, using urethane-anesthetized rats, we examined the dose-dependent effects of intravenous (IV) injection of various doses of anserine, dipeptide of similar structure to L-carnosine, on RSNA, BP and heart rate (HR). We found that injection of a low dose of anserine (1 microg) significantly suppressed RSNA, BP and HR. Conversely, a high dose (1000 microg) of anserine significantly elevated RSNA, BP and HR. Pretreatment with lateral cerebral ventricular (LCV) injection of thioperamide, a histaminergic H(3)-receptor antagonist, eliminated the effects of a low dose of anserine on RSNA, BP and HR. LCV injection of diphenhydramine, a histaminergic H(1)-receptor antagonist, abolished the effects of a high dose of anserine on RSNA, BP and HR. These findings suggest that anserine affects RSNA, BP and HR in a dose-dependent manner, and that the histaminergic nerve may be involved in the dose-different effects of anserine in rats. PMID:19537934

Tanida, M; Shen, J; Kubomura, D; Nagai, K

2010-01-01

346

Alpha-synuclein oligomerization in manganese-induced nerve cell injury in brain slices: a role of NO-mediated S-nitrosylation of protein disulfide isomerase.  

Science.gov (United States)

Over-exposure to manganese (Mn) has been known to induce endoplasmic reticulum (ER) stress involving protein misfolding. The proper maturation and folding of native proteins rely on the activity of protein disulfide isomerase (PDI). However, the exact mechanism of Mn-induced alpha-synuclein oligomerization is unclear. To explore whether alpha-synuclein oligomerization was associated with S-nitrosylation of PDI, we made the rat brain slice model of manganism and pretreated slices with L-Canavanine, a selective iNOS inhibitor. After slices were treated with Mn (0, 25, 100, and 400 ?M) for 24 h, there were dose-dependent increases in apoptotic percentage of cells, lactate dehydrogenase (LDH) releases, production of NO, inducible nitric oxide synthase (iNOS) activity, the mRNA and protein expressions of iNOS, and PDI. Moreover, S-nitrosylated PDI and alpha-synuclein oligomerization also increased. However, there was a significant increase in the PDI activity of 25-?M Mn-treated slices. Then, PDI activity and the affinity between PDI and alpha-synuclein decreased significantly in response to Mn (100 and 400 ?M), which was associated with S-nitrosylation of PDI. The results indicated that S-nitrosylated PDI could affect its activity. We use the L-Canavanine pretreatment brain slices to inhibit S-nitrosylation of PDI. The results showed that L-Canavanine pretreatment could reduce Mn-induced nerve cell injury and alpha-synuclein oligomerization. Additionally, there was a significant recovery in PDI activity in L-Canavanine-pretreated slices. The findings revealed that Mn induced nitrosative stress via the activation of iNOS and subsequent S-nitrosylation of PDI in cultured slices. Moreover, S-nitrosylation of PDI is an important signaling event in the Mn-induced alpha-synuclein oligomerization in brain slices. PMID:24777576

Xu, Bin; Jin, Cui-Hong; Deng, Yu; Liu, Wei; Yang, Tian-Yao; Feng, Shu; Xu, Zhao-Fa

2014-12-01

347

Calcitonin gene-related peptide in thyroid nerve fibers and C cells: effects on thyroid hormone secretion and response to hypercalcemia.  

Science.gov (United States)

Calcitonin gene-related peptide (CGRP) in the thyroid has a dual localization to nerve fibers around blood vessels and follicles and to parafollicular (C) cells. CGRP was found to coexist with substance P (SP) in most of the nerve fibers; a few CGRP fibers seemed to lack SP, and a few SP fibers seemed to be devoid of CGRP. In the C cells, CGRP coexisted with calcitonin (CT). Cervical vagotomy (extirpation of the nodose ganglion) eliminated approximately 50% of the CGRP/SP fibers in the thyroid without any overt influence on CGRP/CT in the C cells. Removal of the superior cervical ganglion or chemical sympathectomy (6-hydroxydopamine treatment) affected neither thyroid CGRP/SP nerve fibers nor CGRP/CT-storing C cells. CGRP nerve cell bodies were numerous in the jugular-nodose ganglionic complex (notably in the jugular portion); in many of them, CGRP coexisted with SP. A few scattered CGRP nerve cell bodies also occurred in the laryngeal ganglion, whereas none was found in the thyroid ganglion. Hypercalcemia evoked by vitamin D2 treatment, which is known to degranulate thyroid C cells, reduced the thyroid content of both CGRP and CT. As tested in mice in vivo, CGRP and SP alone or together had no effect on basal or TSH- or isoprenaline-induced thyroid hormone secretion. Vasoactive intestinal peptide-stimulated iodothyronine release, on the other hand, was enhanced by CGRP, but not by SP. SP had no effect on combined vasoactive intestinal peptide-CGRP-stimulated iodothyronine release. These findings suggest that CGRP participates in the control of thyroid hormone secretion and that, like CT, CGRP in the C cells is under control of the serum calcium level. PMID:3095106

Grunditz, T; Ekman, R; Håkanson, R; Rerup, C; Sundler, F; Uddman, R

1986-11-01

348

Correlation between the ganglion cell complex and structural measures of the optic disc and retinal nerve fiber layer in glaucoma.  

Science.gov (United States)

To correlate the ganglion cell complex (GCC) parameters with structural measures of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) as evaluated by Fourier-Domain optic coherence tomography (OCT). This retrospective study included patients with glaucoma, ocular hypertensive patients and glaucoma suspects who had previously undergone OCT examination with the RTVue-100. The parameters of GCC (average, superior, inferior, focal loss volume [FLV], global loss volume [GLV]) were correlated with the values of the ONH (cup volume, cup area, horizontal cup-to-disk ratio, vertical cup-to-disk ratio, and rim area) and RNFL (average, superior, and inferior) using Pearson's correlation coefficient. The sample included 74 eyes of 37 patients. All correlations between GCC parameters and RNFL were strong (r > 0.60). The correlation between GCC parameters and ONH were good for most parameters, except that for FLV and cup volume (r = 0.13), GLV and cup volume (r = 0.09), and GLV and cup area (r = 0.21). The GCC parameters can be used as structural measures of the glaucomatous optic neuropathy. PMID:25183459

Bresciani-Battilana, Erica; Teixeira, Ivan C; Barbosa, Diego T Q; Caixeta-Umbelino, Cristiano; Paolera, Maurício D; Kasahara, Niro

2014-09-01

349

Mechanism of Cl- sensitivity in internal ion receptors of the leech: an inward current gated off by Cl- in the nephridial nerve cells.  

Science.gov (United States)

The nephridial nerve cells of the leech, Hirudo medicinalis, 34 sensory cells, each associated with one nephridium, are sensitive to changes in extracellular Cl- concentration, an important factor in ion homeostasis. Using single-electrode current- and voltage clamp and ion substitution techniques, the specificity and mechanism of Cl- sensitivity of the nephridial nerve cell was studied in isolated preparations. Increase of the normally low external Cl- concentration leads to immediate and sustained hyperpolarization, decrease of the frequency of bursts and decrease of membrane conductance. The response is halogen specific: Cl- can be replaced by Br-, but not by organic mono- or divalent anions or inorganic divalent anions. At physiological Cl- concentrations (36 mM extracellular Cl-), the nephridial nerve cell has a high resting conductance for Cl- and the membrane potential is governed by Cl-. In high extracellular Cl- concentrations (110-130 mM), membrane conductance is low, most likely due to the gating off of Cl- channels. Under these conditions, membrane potential is dominated by the K+ distribution and the nephridial nerve cell hyperpolarizes towards EK. PMID:2033568

Wenning, A; Calabrese, R L

1991-01-01

350

Telomerase expression and proliferative activity suggest a stem cell role for thyroid solid cell nests.  

Science.gov (United States)

Solid cell nests of the human thyroid gland are composed of main cells and C cells. In order to investigate the putative stem cell nature of the role for solid cell nests, we evaluated the histological features, and the immunohistochemical expression of p63, bcl-2, telomerase catalytic subunit, and two proliferative markers (Ki-67 and minichromosome maintenance protein 2), in a series of 24 cases of solid cell nests. Proliferative indices were determined in (a) solid cell nests, (b) thyroid follicular cells in the vicinity of solid cell nests within a low-power field, and (c) distant thyroid tissue, at a distance of at least three low-power fields from solid cell nests. In 15 cases of solid cell nests (62.5%), mixed follicles were observed; papillary formations were observed in four cases (16.6%), and ciliated cells were observed in the lining of microcysts associated with two cases (8.3%). Salivary gland-type tissue, cartilage islands, adipose and fibrous tissues, and small nerves were also associated with some cases of solid cell nests. We observed that the main cells of the solid cell nests express consistently telomerase, although at lower levels than p63, and show strong cytoplasmic immunoreactivity for bcl-2, which is associated with an increased differentiation potential. We also observed that despite their relative low proliferative index, main cells of the solid cell nests display higher proliferation than follicular cells in the vicinity and follicular cells in more distant thyroid tissue. We conclude that main cells of the solid cell nests apparently harbor the minimal properties of a stem cell phenotype (capacity for both self-renewal, conferred by telomerase activity, and differentiation to one or more than one type of specialized cells, given by the high expression of p63 and bcl-2) and may thus represent a pool of stem cells of the adult thyroid. PMID:15044923

Preto, Ana; Cameselle-Teijeiro, José; Moldes-Boullosa, Julio; Soares, Paula; Cameselle-Teijeiro, Jorge F; Silva, Paula; Reis-Filho, Jorge S; Reyes-Santías, Rosa M; Alfonsín-Barreiro, Natividad; Forteza, Jerónimo; Sobrinho-Simões, Manuel

2004-07-01

351

K-252a, a potent protein kinase inhibitor, blocks nerve growth factor- induced neurite outgrowth and changes in the phosphorylation of proteins in PC12h cells  

OpenAIRE

Nerve growth factor (NGF) promotes neuronal differentiation of PC12 pheochromocytoma cells. One of the most prominent and distinguishing features of neuronal differentiation is neurite outgrowth. The mechanism by which NGF causes the cells to elaborate neurites is unknown. This study shows that K-252a, a potent protein kinase inhibitor, blocks NGF-induced neurite outgrowth and the changes in protein phosphorylation elicited by NGF. In the experiment with intact cells phosphorylated with 32P-o...

1988-01-01

352

Structural and functional association between substance P- and calcitonin gene-related peptide-immunoreactive nerves and accessory cells in the rat dental pulp.  

Science.gov (United States)

Defense mechanisms of the dentin/pulp complex involve a variety of biological systems in which immunocompetent cells, the nervous system, and the vascular supply play important roles. In the present study, pulpal accessory cells were examined regarding (i) their structural relationship to nerves and (ii) how the functional capacities of these cells were affected by neuropeptides. Micro-anatomic association was investigated in the normal rat molar pulp with the use of double-immunofluorescence staining and dual-channel confocal laser scanning microscopy. Examinations of confocal laser scanning microscopic images from single focal planes revealed the presence of apparent contacts between thin, varicose nerve fibers and immunocompetent cells, indicating proximity between these two structures. The close associations were most frequently observed in the para-odontoblastic region of the coronal pulp, where more than 70% of class II antigen-expressing (OX6+) cells showed proximity to nerve fibers immunoreactive to calcitonin gene-related peptide. The corresponding figure for substance P was about 50%. ED2+ macrophages closely associated with nerves were less frequently observed. Functional studies conducted in vitro demonstrated that 10(-9) to 10(-7) mol/L of substance P significantly increased (p < 0.05), while 10(-7) to 10(-6) mol/L of calcitonin gene-related peptide suppressed (p < 0.01) proliferation of purified T-lymphocytes stimulated with sub-optimal concentrations of concanavalin A in the presence of rat incisor pulpal cells as accessory cells. These data suggest that pulpal sensory nerve fibers and their products may have an influence upon the immune defense of the dental pulp. PMID:9390474

Okiji, T; Jontell, M; Belichenko, P; Dahlgren, U; Bergenholtz, G; Dahlström, A

1997-12-01

353

Influence of intrathecal delivery of bone marrow-derived mesenchymal stem cells on spinal inflammation and pain hypersensitivity in a rat model of peripheral nerve injury.  

Science.gov (United States)

BackgroundMultipotent mesenchymal stem (stromal) cells (MSCs) have been credited with immunomodulative properties, supporting beneficial outcomes when transplanted into a variety of disease models involving inflammation. Potential mechanisms include the secretion of paracrine factors and the establishment of a neurotrophic microenvironment. To test the hypothesis that MSCs release soluble mediators that can attenuate local inflammation, we here analysed the influence of MSCs on the activation of microglia cells, as well as on inflammatory parameters and pain behaviour in a surgical rat model of neuropathic pain.MethodsWe focussed on an experimental model of partial sciatic nerve ligation (PSNL), characterised by a rapid and persistent inflammation in the dorsal lumbar spinal cord where sensory inputs from the sciatic nerve are processed. Via indwelling intrathecal catheters, MSCs were repetitively grafted into the intrathecal lumbar space. Animals were evaluated for mechanical and thermal hypersensitivity over a period of 21 days after PSNL. Afterwards, spinal cords were processed for immunohistochemical analysis of the microglial marker ionized calcium-binding adapter molecule 1 (Iba1) and quantification of inflammatory markers in ipsilateral dorsal horns. We hypothesised that injections on postsurgical days 2 to 4 would interfere with microglial activation, leading to a reduced production of pro-inflammatory cytokines and amelioration of pain behaviour.ResultsPSNL-induced mechanical allodynia or heat hyperalgesia were not influenced by MSC transplantation, and spinal cord inflammatory processes remained largely unaffected. Indeed, the early microglial response to PSNL characterised by increased Iba1 expression in the lumbar dorsal horn was not significantly altered and cytokine levels in the spinal cord at 21 days after surgery were similar to those found in vehicle-injected animals. Grafted MSCs were detected close to the pia mater, but were absent within the spinal cord parenchyma.ConclusionsWe conclude that intrathecal administration is not an appropriate route to deliver cells for treatment of acute spinal cord inflammation as it leads to entrapment of grafted cells within the pia mater. We propose that the early inflammatory response triggered by PSNL in the lumbar spinal cord failed to effectively recruit MSCs or was insufficient to disturb the tissue integrity so as to allow MSCs to penetrate the spinal cord parenchyma. PMID:25212534

Schäfer, Sabrina; Berger, Julie V; Deumens, Ronald; Goursaud, Stéphanie; Hanisch, Uwe-Karsten; Hermans, Emmanuel

2014-09-12

354

Human PLacental eXpanded (PLX) mesenchymal-like adherent stromal cells confer neuroprotection to nerve growth factor (NGF)-differentiated PC12 cells exposed to ischemia by secretion of IL-6 and VEGF.  

Science.gov (United States)

Mesenchymal stem cells are potent candidates in stroke therapy due to their ability to secrete protective anti-inflammatory cytokines and growth factors. We investigated the neuroprotective effects of human placental mesenchymal-like adherent stromal cells (PLX) using an established ischemic model of nerve growth factor (NGF)-differentiated pheochromocytoma PC12 cells exposed to oxygen and glucose deprivation (OGD) followed by reperfusion. Under optimal conditions, 2×10(5) PLX cells, added in a trans-well system, conferred 30-60% neuroprotection to PC12 cells subjected to ischemic insult. PC12 cell death, measured by LDH release, was reduced by PLX cells or by conditioned medium derived from PLX cells exposed to ischemia, suggesting the active release of factorial components. Since neuroprotection is a prominent function of the cytokine IL-6 and the angiogenic factor VEGF165, we measured their secretion using selective ELISA of the cells under ischemic or normoxic conditions. IL-6 and VEGF165 secretion by co-culture of PC12 and PLX cells was significantly higher under ischemic compared to normoxic conditions. Exogenous supplementation of 10ng/ml each of IL-6 and VEGF165 to insulted PC12 cells conferred neuroprotection, reminiscent of the neuroprotective effect of PLX cells or their conditioned medium. Growth factors as well as co-culture conditioned medium effects were reduced by 70% and 20% upon pretreatment with 240ng/ml Semaxanib (anti VEGF165) and/or 400ng/ml neutralizing anti IL-6 antibody, respectively. Therefore, PLX-induced neuroprotection in ischemic PC12 cells may be partially explained by IL-6 and VEGF165 secretion. These findings may also account for the therapeutic effects seen in clinical trials after treatment with these cells. PMID:25450973

Lahiani, Adi; Zahavi, Efrat; Netzer, Nir; Ofir, Racheli; Pinzur, Lena; Raveh, Shani; Arien-Zakay, Hadar; Yavin, Ephraim; Lazarovici, Philip

2015-02-01

355

P75 nerve growth factor receptors modulate development of GnRH neurons and olfactory ensheating cells  

Science.gov (United States)

Temporal and spatial localization of nerve growth factor receptor (p75NGFR) in the developing olfactory system and gonadotropin-releasing hormone-1 (GnRH) system was characterized and its role analyzed using p75NGFR null mice and nasal explants. Prenatally, p75NGFR was expressed by GnRH neurons and olfactory ensheathing cells (OECs). In p75NGFR null mice, no change in the number of GnRH cells was detected as compared to wild-type. However, in null mice, a shift in the distribution of GnRH neurons was found, with a small population of GnRH cells migrating further caudally toward the median eminence. Additionally, a reduction of both GAD67 positive olfactory axons and GFAP positive OEC fibers occurred. Acute administration of a p75NGFR blocker to GnRH cells maintained in vitro increased migration rate, consistent with the change in distribution detected in p75NGFR null mice. Chronic inhibition of p75NGFR caused an attenuation of olfactory axon fasciculation and a decrease in OEC density, again mimicking the changes detected in null mice. However, a reduction in GnRH cell number was found after chronic treatment that not observed in KO animals suggesting indirect changes occur during chronic treatment in vitro and/or a compensatory mechanism occurs in vivo that prevents loss of GnRH neurons in the absence of p75NGFR. PMID:24409113

Raucci, Franca; Tiong, Jean D.; Wray, Susan

2013-01-01

356

P75 nerve growth factor receptors modulate development of GnRH neurons and olfactory ensheating cells  

Directory of Open Access Journals (Sweden)

Full Text Available Temporal and spatial localization of nerve growth factor receptor (p75NGFR in the developing olfactory system and gonadotropin-releasing hormone-1 (GnRH system was characterized and its role analyzed using p75NGFR null mice and nasal explants. Prenatally, p75NGFR was expressed by GnRH neurons and olfactory ensheathing cells (OECs. In p75NGFR null mice, no change in the number of GnRH cells was detected as compared to wild-type. However, in null mice, a shift in the distribution of GnRH neurons was found, with a small population of GnRH cells migrating further caudally toward the median eminence. Additionally, a reduction of both GAD67 positive olfactory axons and GFAP positive OEC fibers occurred. Acute administration of a p75NGFR blocker to GnRH cells maintained in vitro increased migration rate, consistent with the change in distribution detected in p75NGFR null mice. Chronic inhibition of p75NGFR caused an attenuation of olfactory axon fasciculation and a decrease in OEC density, again mimicking the changes detected in null mice. However, a reduction in GnRH cell number was found after chronic treatment that not observed in KO animals suggesting indirect changes occur during chronic treatment in vitro and/or a compensatory mechanism occurs in vivo that prevents loss of GnRH neurons in the absence of p75NGFR.

FrancaRaucci

2013-12-01

357

Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity  

OpenAIRE

Mast cells (MCs) are tissue resident immune cells that participate in a variety of allergic and other inflammatory conditions. In most tissues, MCs are found in close proximity to nerve endings of primary afferent neurons that signal pain (i.e. nociceptors). Activation of MCs causes the release of a plethora of mediators that can activate these nociceptors and promote pain. Although MCs are ubiquitous, conditions associated with systemic MC activation give rise primarily to two major types of...

Levy, Dan; Kainz, Vanessa; Burstein, Rami; Strassman, Andrew M.

2011-01-01

358

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.)

359

The dual phosphatase activity of synaptojanin1 is required for both efficient synaptic vesicle endocytosis and reavailability at nerve terminals.  

Science.gov (United States)

Phosphoinositides have been implicated in synaptic vesicle recycling largely based on studies of enzymes that regulate phosphoinositide synthesis and hydrolysis. One such enzyme is synaptojanin1, a multifunctional protein conserved from yeast to humans, which contains two phosphoinositol phosphatase domains and a proline-rich domain. Genetic ablation of synaptojanin1 leads to pleiotropic defects in presynaptic function, including accumulation of free clathrin-coated vesicles and delayed vesicle reavailability, implicating this enzyme in postendocytic uncoating of vesicles. To further elucidate the role of synaptojanin1 at nerve terminals, we performed quantitative synaptic vesicle recycling assays in synj1(-/-) neurons. Our studies show that synaptojanin1 is also required for normal vesicle endocytosis. Defects in both endocytosis and postendocytic vesicle reavailability can be fully restored upon reintroduction of synaptojanin1. However, expression of synaptojanin1 with mutations abolishing catalytic activity of each phosphatase domain reveals that the dual action of both domains is required for normal synaptic vesicle internalization and reavailability. PMID:18093523

Mani, Meera; Lee, Sang Yoon; Lucast, Louise; Cremona, Ottavio; Di Paolo, Gilbert; De Camilli, Pietro; Ryan, Timothy A

2007-12-20

360

Neuromodulatory loop mediated by nerve growth factor and interleukin 6 in thymic stromal cell cultures.  

OpenAIRE

Neural crest cell derivatives have been suggested to be involved in thymus development. We established nonlymphoid thymic stromal cell cultures capable of supporting T-cell differentiation. In these nonlymphoid cell cultures, we identified cells with phenotypic and biochemical markers specific for neuronal cells. Neurofilament mRNA and 68- and 160-kDa neurofilament proteins, as well as 74-kDa synapsin I isoform, were expressed in many of the cultured cells. For example, neurofilament immunore...

Screpanti, I.; Meco, D.; Scarpa, S.; Morrone, S.; Frati, L.; Gulino, A.; Modesti, A.

1992-01-01

361

Nerve growth factor-induced circadian phase shifts and MAP kinase activation in the hamster suprachiasmatic nuclei.  

Science.gov (United States)

Circadian rhythms are entrained by light and by several neurochemical stimuli. In hamsters housed in constant darkness, i.c.v. administration of nerve growth factor (NGF) at various times in their circadian cycle produced phase shifts of locomotor activity rhythms that were similar in direction and circadian timing to those produced by brief pulses of light. Moreover, the effect of NGF and light were not additive, indicating signalling points in common. These points include the immediate-early gene c-fos and ERK1/2, a component of the mitogen-activated protein kinases (MAPK) family. NGF activates c-FOS and ERK1/2-MAPK in the suprachiasmatic nuclei, the site of a circadian clock in mammals, when administered during the subjective night but not during the day. The effect of NGF on ERK1/2 activation was not inhibited by the administration of MK-801, a glutamate/NMDA receptor antagonist. These results suggest that NGF, acting through MAPK activation, plays a role in photic entrainment of the mammalian circadian clock. PMID:16101748

Pizzio, Gastón A; Hainich, Ernesto C; Plano, Santiago A; Ralph, Martin R; Golombek, Diego A

2005-08-01

362

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)

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.

Chrzaszcz MaryAnn

2010-05-01

363

Improving the Catalytic Activity of Hyperthermophilic Pyrococcus horikoshii Prolidase for Detoxification of Organophosphorus Nerve Agents over a Broad Range of Temperatures  

OpenAIRE

Prolidases hydrolyze Xaa-Pro dipeptides and can also cleave the P-F and P-O bonds found in organophosphorus (OP) compounds, including the nerve agents soman and sarin. Ph1prol (PH0974) has previously been isolated and characterized from Pyrococcus horikoshii and was shown to have higher catalytic activity over a broader pH range, higher affinity for metal, and increased thermostability compared to P. furiosus prolidase, Pfprol (PF1343). To obtain a better enzyme for OP nerve agent decontamin...

Theriot, Casey M.; Semcer, Rebecca L.; Shah, Saumil S.; Grunden, Amy M.

2011-01-01

364

Nerve Control of Blood Vessel Patterning  

Science.gov (United States)

Patterning of embryonic blood vessels occurs in association with nerves. In this issue of Developmental Cell, Li et al. (2013) report that nerve-derived chemokine Cxcl12 (also known as SDF-1), acting through its receptor Cxcr4, initiates blood vessel remodeling along cutaneous nerve trajectories to establish the proper pattern of cutaneous arteries. PMID:23449469

Makita, Takako

2013-01-01

365

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

OpenAIRE

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...

Liang, Lingli; Tao, Bo; Fan, Longchang; Yaster, Myron; Zhang, Yi; Tao, Yuan-xiang

2013-01-01

366

Nerve growth factor rapidly stimulates tyrosine phosphorylation of phospholipase C-gamma 1 by a kinase activity associated with the product of the trk protooncogene.  

OpenAIRE

Nerve growth factor (NGF) promotes the survival and differentiation of specific populations of neurons. The molecular mechanisms by which cells respond to NGF are poorly understood, but two clues have emerged recently. First, NGF rapidly stimulates tyrosine phosphorylation of several unidentified proteins in the NGF-responsive pheochromocytoma cell line PC12 [Maher, P. (1988) Proc. Natl. Acad. Sci. USA 85, 6788-6791]. Second, the protein-tyrosine kinase encoded by the protooncogene trk (p140t...

Vetter, M. L.; Martin-zanca, D.; Parada, L. F.; Bishop, J. M.; Kaplan, D. R.

1991-01-01

367

Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain  

International Nuclear Information System (INIS)

Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sitereplete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF

368

Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain  

Energy Technology Data Exchange (ETDEWEB)

Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF.

Altar, C.A.; Burton, L.E.; Bennett, G.L.; Dugich-Djordjevic, M. (Genentech, Inc., South San Francisco, CA (USA))

1991-01-01

369

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

DEFF Research Database (Denmark)

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.

Fjord-Larsen, L; Kusk, P

2010-01-01

370

An afferent vagal nerve pathway links hepatic PPARalpha activation to glucocorticoid-induced insulin resistance and hypertension.  

Science.gov (United States)

Glucocorticoid excess causes insulin resistance and hypertension. Hepatic expression of PPARalpha (Ppara) is required for glucocorticoid-induced insulin resistance. Here we demonstrate that afferent fibers of the vagus nerve interface with hepatic Ppara expression to disrupt blood pressure and glucose homeostasis in response to glucocorticoids. Selective hepatic vagotomy decreased hyperglycemia, hyperinsulinemia, hepatic insulin resistance, Ppara expression, and phosphoenolpyruvate carboxykinase (PEPCK) enzyme activity in dexamethasone-treated Ppara(+/+) mice. Selective vagotomy also decreased blood pressure, adrenergic tone, renin activity, and urinary sodium retention in these mice. Hepatic reconstitution of Ppara in nondiabetic, normotensive dexamethasone-treated PPARalpha null mice increased glucose, insulin, hepatic PEPCK enzyme activity, blood pressure, and renin activity in sham-operated animals but not hepatic-vagotomized animals. Disruption of vagal afferent fibers by chemical or surgical means prevented glucocorticoid-induced metabolic derangements. We conclude that a dynamic interaction between hepatic Ppara expression and a vagal afferent pathway is essential for glucocorticoid induction of diabetes and hypertension. PMID:17276352

Bernal-Mizrachi, Carlos; Xiaozhong, Liu; Yin, Li; Knutsen, Russell H; Howard, Michael J; Arends, Joop J A; Desantis, Pascual; Coleman, Trey; Semenkovich, Clay F

2007-02-01

371

Axonal trajectories of inhibitory vestibulocollic neurons activated by the anterior semicircular canal nerve and their synaptic effects on neck motoneurons in the cat.  

Science.gov (United States)

Somatic location, axonal trajectories and synaptic effects of inhibitory vestibulocollic neurons which were activated by selective stimulation of the anterior semicircular canal nerve (ACN) were studied in the anesthetized cat. ACN stimulation evoked disynaptic inhibitory postsynaptic potentials (IPSPs) in neck flexor motoneurons. This was seen in all the (64/64) tested motoneurons innervating the ipsilateral (i-) longus capitis (LC) and the i-sternocleidomastoideus (SCM) muscles and in 86% (38/44) of the motoneurons innervating the contralateral (c-) LC muscle. The inhibitory relay neurons, identified by orthodromic and antidromic responses to stimulation of the ACN and the i- and c-LC motoneuron pools, were classified as VCi (vestibulocollic neurons sending an axon to the i-LC motoneuron pool) and VCc (vestibulocollic neurons sending an axon to the c-LC motoneuron pool) neurons. Neither VCi nor VCc neurons were activated antidromically by localized stimulation of the ascending medial longitudinal fasciculus (asc. MLF) or the 3rd nuclei. They were located in the medial, descending and ventral lateral vestibular nuclei. It was also observed that VCi neurons produced unitary IPSPs in i-LC and i-SCM motoneurons in the C1 segment. Inhibitory synapses were estimated to be on the cell somata and/or the proximal dendrites of the motoneurons. PMID:2257898

Uchino, Y; Isu, N; Sakuma, A; Ichikawa, T; Hiranuma, K

1990-01-01

372

Heparin modulation of the neurotropic effects of acidic and basic fibroblast growth factors and nerve growth factor on PC12 cells  

International Nuclear Information System (INIS)

Nerve growth factor (NGF) and acidic or basic fibroblast growth factor (aFGF and bFGF, respectively) induce neurite outgrowth from the rat pheochromocytoma cell line, PC12. The neurites induced by these three factors are stable for up to a month in cell culture in the continued presence of any of the above growth factors. bFGF (ED50 = 30 pg/ml) is 800 fold more potent in stimulating neurite outgrowth than aFGF (ED50 = 25 ng/ml) and 260 fold more potent than NGF (ED50 = 8 ng/ml). While the neurotropic activities of aFGF and NGF are potentiated by heparin, that of bFGF is both partially inhibited or stimulated, depending upon the concentration of bFGF. Radioreceptor binding experiments show that aFGF and bFGF bind to a common binding site on the PC12 cell surface. Affinity labeling studies demonstrate a single receptor with an apparent molecular weight of 145,000 daltons, which corresponds to the high molecular weight receptor identified in BHK-21 cells. NGF does not appear to compete with aFGF or bFGF for binding to the receptor. Heparin blocked the binding of bFGF to the receptor but had only a small inhibitory effect on the binding of aFGF to the receptor. Thus, it appears that heparin inhibition of the neurotropic effects of bFGF occurs, at least in part, by impairing the interaction of bFGF with the receptor, while having little effect on that of aFGF. The stimulatory effects of heparin on the neurotropic activity of aFGF, bFGF, and NGF may occur through a site notbFGF, and NGF may occur through a site not associated with the respective cellular receptor for the growth factors

373

Nerve growth factor affects Ca2+ currents via the p75 receptor to enhance prolactin mRNA levels in GH3 rat pituitary cells.  

Science.gov (United States)

In clonal pituitary GH(3) cells, spontaneous action potentials drive the opening of Ca(v)1 (L-type) channels, leading to Ca(2+) transients that are coupled to prolactin gene transcription. Nerve growth factor (NGF) has been shown to stimulate prolactin synthesis by GH(3) cells, but the underlying mechanisms are unknown. Here we studied whether NGF influences prolactin gene expression and Ca(2+) currents. By using RT-PCR, NGF (50 ng ml(-1)) was found to augment prolactin mRNA levels by approximately 80% when applied to GH(3) cells for 3 days. A parallel change in the prolactin content was detected by Western blotting. Both NGF-induced responses were mimicked by an agonist (Bay K 8644) and prevented by a blocker (nimodipine) of L-type channels. In whole-cell patch-clamp experiments, NGF enhanced the L-type Ca(2+) current by approximately 2-fold within 60 min. This effect reversed quickly upon growth factor withdrawal, but was maintained for days in the continued presence of NGF. In addition, chronic treatment (>or= 24 h) with NGF amplified the T-type current, which flows through Ca(v)3 channels and is thought to support pacemaking activity. Thus, NGF probably increases the amount of Ca(2+) that enters per action potential and may also induce a late increase in spike frequency. MC192, a specific antibody for the p75 neurotrophin receptor, but not tyrosine kinase inhibitors (K252a and lavendustin A), blocked the effects of NGF on Ca(2+) currents. Overall, the results indicate that NGF activates the p75 receptor to cause a prolonged increase in Ca(2+) influx through L-type channels, which in turn up-regulates the prolactin mRNA. PMID:16690703

López-Domínguez, Adriana M; Espinosa, Juan Luis; Navarrete, Araceli; Avila, Guillermo; Cota, Gabriel

2006-07-15

374

Depletion of Foxp3+ regulatory T cells increases severity of mechanical allodynia and significantly alters systemic cytokine levels following peripheral nerve injury.  

Science.gov (United States)

Neuropathic pain is a debilitating condition caused by damage to the somatosensory nervous system, such as peripheral nerve injury. The immune system, and in particular the adaptive T cell response, plays a key role in mediating such pain. Regulatory T (Treg) cells are a small subpopulation of inhibitory T cells that prevent autoimmunity, limit immunopathology and maintain immune homeostasis. Here, we investigated the effects of conditional depletion of Treg cells on mechanical allodynia and serum cytokines in mice with chronic constriction injury (CCI) of the sciatic nerve, an animal model of neuropathic pain. We demonstrate that CCI induced the infiltration of small numbers of Treg cells within effected neuronal tissue. Utilising the transgenic DEREG (DEpletion of REGulatory T cells) mice, we confirmed effective depletion of Foxp3+ Treg cells by diphtheria toxin injections. Following CCI we observed a transient, though significant, increase in pain hypersensitivity for Treg-depleted DEREG mice compared to non-Treg-depleted mice. Analysis of systemic cytokine levels demonstrated significant changes in serum cytokine expression profiles. In particular, we observed significant increases in systemic concentration of RANTES, IL-2 and IL-5, and significant decreases in IL-12 and IFN-? in nerve-injured Treg-depleted DEREG mice. Further analysis indicated a substantial increase in the serum concentration of IL-12p40 as a direct result of Treg cell depletion. These results suggest that depletion of Foxp3+ Treg cells promote nerve injury-induced pain hypersensitivity, partially by inducing altered systemic concentrations of cytokines, which may act to regulate neuropathic pain. PMID:25461400

Lees, Justin G; Duffy, Samuel S; Perera, Chamini J; Moalem-Taylor, Gila

2014-11-20

375

Monoclonal antibodies to the cell surface and a soluble form of the human nerve growth factor receptor  

Energy Technology Data Exchange (ETDEWEB)

Monoclonal antibodies (designated IIIG5, VIID1, VIIIC8, and XIF1) have been produced that bind to the human nerve growth factor receptor (NGF-R) as well as to a soluble, truncated form of the receptor (NGF-Rt). The antibodies were generated against partially purified NGF-Rt from the conditioned medium of E9b cells, a transfected mouse fibroblast cell line (Ltk-) that expresses large numbers of the low affinity form of the human NGF-R on its cell surface. Hybridomas were screened by radiometric immunosorbent assay (RISA) and by immunoprecipitation of solubilized cell surface receptor covalently cross-linked to {sup 125}I-NGF. Four positive lines were cloned by limiting dilution and were found to secrete monoclonal antibodies of the IgGl,k subclass. All monoclonal antibodies bound to both NGF-R and NGF-Rt. Two monoclonal antibodies (VIID1, XIF1) immunoblotted the NGF-R from E9b cell preparations resolved on non-reducing sodium dodecyl sulfate (SDS)-polyacrylamide gels. The antibodies immunoprecipitated NGF-R from both E9b cells and from SH-SY5Y human neuroblastoma cells. The monoclonal antibodies bound to monkey (rhesis and cynomolgus) NGF-Rt, but did not cross-react with NGF-R from chick or rat. Results of antibody competition studies demonstrated that three antibodies bound to a similar or overlapping epitope on the NGF-Rt and one monoclonal antibody (IIIG5) recognized a distinct receptor epitope. Antibodies that bound to different sites on the receptor were used to develop a sensitive 2-site RISA. The 2-site RISA can be used to rapidly quantitate NGF-R and NGF-Rt in large numbers of biological samples in the absence of added {sup 125}I-labeled NGF.

Clagett-Dame, M.; Chung, C.; Chao, M.V.; DiStefano, P.S. (Univ. of Wisconsin, Madison (USA))

1990-12-01

376

Monoclonal antibodies to the cell surface and a soluble form of the human nerve growth factor receptor  

International Nuclear Information System (INIS)

Monoclonal antibodies (designated IIIG5, VIID1, VIIIC8, and XIF1) have been produced that bind to the human nerve growth factor receptor (NGF-R) as well as to a soluble, truncated form of the receptor (NGF-Rt). The antibodies were generated against partially purified NGF-Rt from the conditioned medium of E9b cells, a transfected mouse fibroblast cell line (Ltk-) that expresses large numbers of the low affinity form of the human NGF-R on its cell surface. Hybridomas were screened by radiometric immunosorbent assay (RISA) and by immunoprecipitation of solubilized cell surface receptor covalently cross-linked to 125I-NGF. Four positive lines were cloned by limiting dilution and were found to secrete monoclonal antibodies of the IgGl,k subclass. All monoclonal antibodies bound to both NGF-R and NGF-Rt. Two monoclonal antibodies (VIID1, XIF1) immunoblotted the NGF-R from E9b cell preparations resolved on non-reducing sodium dodecyl sulfate (SDS)-polyacrylamide gels. The antibodies immunoprecipitated NGF-R from both E9b cells and from SH-SY5Y human neuroblastoma cells. The monoclonal antibodies bound to monkey (rhesis and cynomolgus) NGF-Rt, but did not cross-react with NGF-R from chick or rat. Results of antibody competition studies demonstrated that three antibodies bound to a similar or overlapping epitope on the NGF-Rt and one monoclonal antibody (IIIG5) recognized a distinct receptor epitope. Antibodies that bound to different sites on the receptor were used different sites on the receptor were used to develop a sensitive 2-site RISA. The 2-site RISA can be used to rapidly quantitate NGF-R and NGF-Rt in large numbers of biological samples in the absence of added 125I-labeled NGF

377

Characterizing the behavioral effects of nerve agent-induced seizure activity in rats: increased startle reactivity and perseverative behavior.  

Science.gov (United States)

The development and deployment of next-generation therapeutics to protect military and civilian personnel against chemical warfare nerve agent threats require the establishment and validation of animal models. The purpose of the present investigation was to characterize the behavioral consequences of soman (GD)-induced seizure activity using a series of behavioral assessments. Male Sprague-Dawley rats (n=24), implanted with a transmitter for telemetric recording of encephalographic signals, were administered either saline or 1.0 LD?? GD (110 ?g/kg, sc) followed by treatment with a combination of atropine sulfate (2 mg/kg, im) and the oxime HI-6 (93.6 mg/kg, im) at 1 min post-exposure. Seizure activity was allowed to continue for 30 min before administration of the anticonvulsant diazepam (10 mg/kg, sc). The animals that received GD and experienced seizure activity had elevated startle responses to both 100- and 120-dB startle stimuli compared to control animals. The GD-exposed animals that had seizure activity also exhibited diminished prepulse inhibition in response to 120-dB startle stimuli, indicating altered sensorimotor gating. The animals were subsequently evaluated for the acquisition of lever pressing using an autoshaping procedure. Animals that experienced seizure activity engaged in more goal-directed (i.e., head entries into the food trough) behavior than did control animals. There were, however, no differences between groups in the number of lever presses made during 15 sessions of autoshaping. Finally, the animals were evaluated for the development of fixed-ratio (FR) schedule performance. Animals that experienced GD-induced seizure activity engaged in perseverative food trough-directed behaviors. There were few differences between groups on other measures of FR schedule-controlled behavior. It is concluded that the GD-induced seizure activity increased startle reactivity and engendered perseverative responding and that these measures are useful for assessing the long-term effects of GD exposure in rats. PMID:21983492

Langston, Jeffrey L; Wright, Linnzi K M; Connis, Nick; Lumley, Lucille A

2012-01-01

378

Activation of cytosolic phospholipase A2 in dorsal root ganglion neurons by Ca2+/calmodulin-dependent protein kinase II after peripheral nerve injury  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Peripheral nerve injury leads to a persistent neuropathic pain state in which innocuous stimulation elicits pain behavior (tactile allodynia, but the underlying mechanisms have remained largely unknown. We have previously shown that spinal nerve injury induces the activation of cytosolic phospholipase A2 (cPLA2 in injured dorsal root ganglion (DRG neurons that contribute to tactile allodynia. However, little is known about the signaling pathway that activates cPLA2 after nerve injury. In the present study, we sought to determine the mechanisms underlying cPLA2 activation in injured DRG neurons in an animal model of neuropathic pain, focusing on mitogen-activated protein kinases (MAPKs and Ca2+/calmodulin-dependent protein kinase II (CaMKII. Results Pharmacological inhibition of either p38 or extracellular signal-regulated kinase (ERK in the injured DRG, which led to suppression of the development of tactile allodynia, did not affect cPLA2 phosphorylation and translocation after nerve injury. By contrast, a CaMKII inhibitor prevented the development and expression of nerve injury-induced tactile allodynia and reduced both the level of cPLA2 phosphorylation and the number of DRG neurons showing translocated cPLA2 in response to nerve injury. Applying ATP to cultured DRG neurons increased the level of both phosphorylated cPLA2 and CaMKII in the vicinity of the plasma membrane and caused physical association of these two proteins. In addition, ATP-stimulated cPLA2 and CaMKII phosphorylation were inhibited by both a selective P2X3R/P2X2+3R antagonist and a nonselective voltage-dependent Ca2+ channel (VDCC blocker. Conclusion These results suggest that CaMKII, but not MAPKs, has an important role in cPLA2 activation following peripheral nerve injury, probably through P2X3R/P2X2+3R and VDCCs in primary afferent neurons.

Inoue Kazuhide

2009-05-01

379

Cation-binding sites in trigeminal ganglia and maxillary nerve: unusual reactivity of perikarya, stem axons and satellite cells.  

Science.gov (United States)

We have used the cupric/ferrocyanide reaction to study cation-binding in trigeminal ganglia and maxillary nerve of adult rats. Unmyelinated axons did not react, whereas myelinated axons were stained at nodal, paranodal or cleft sites. At 'nodal' sites, metallic deposits were found in the axoplasm, along the axolemma, and at the extracellular interfaces of the paranodal myelin. At 'paranodal' sites, particles were concentrated in the paranodal axoplasm and in the intracellular spaces of the myelin loops. Most maxillary axons examined at successive sites had all nodal or all paranodal staining, but 13 of 51 had a mixture. In trigeminal ganglia there was no staining of perineurial sheath, endoneurial cells or mast cells. Satellite cells and their basal laminae were prominently stained, with those around small neurons more reactive than those of large neurons. Patches of neuronal membrane on cell bodies were stained, more often for small than large neurons. The axon hillock and proximal stem axon were not stained in some cases, but approximately half the neurons had staining of perikaryal cytoplasm at the axon hillock or a dense asymmetric band in the proximal stem axon. Strong intraaxonal staining was found at the junction between unmyelinated proximal and myelinated distal stem axon. In distal stem axons, staining was found at the first myelin segment and at each successively thicker myelin segment; staining was mostly weak and paranodal, with intensity proportional to myelin thickness. The T-junction between stem and main myelinated axon had nodal or paranodal patterns; unmyelinated T-junctions were not stained. The varied cation-binding patterns in trigeminal ganglia show unusual properties of satellite cells and important differences between stem and main axons. The results that the cell membrane of axon hillock and proximal stem regions of many sensory large and small neurons may have numerous sodium channels and could affect signal propagation. PMID:2451989

Byers, M R; Costello, R J

1988-03-01

380

Effects of ionizing radiation on purinergic signaling modulation in rat brain nerve cells  

International Nuclear Information System (INIS)

Purinergic signaling is composed of three modulatory components: a) source of extracellular nucleotides, b) specific receptor expression for these transmitter molecules and c) ectonucleotidase selection that dictate cell response gradually degradation extracellular nucleotides to nucleosides. ATP acts as a fast excitatory transmitter in the CNS. Postsynaptic actions of ATP are mediated by an extended family of purinergic, P2X receptors, widely expressed throughout the CNS. NTPDases hydrolyse extracellular ATP and ADP to AMP and are responsive for purinergfic termination. To investigate if ionizing irradiation could modulate CNS purinergic signalization we monitored activity of NTPDases and abundance of P2X7 receptor in synaptic plasma membranes after whole-body acute irradiation using low (0,5Gy) or therapeutic (2Gy) doses, 1h i 72h after irradiating juvenile (15-day old) and adult (90-day old) rats. Acute irradiation modulate purinergic system components investigated at the different ways in the rat development brain SPM and in the adult brain dependent of dose and time after irradiation

381

BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage  

Science.gov (United States)

Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of ?-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN). PMID:25243135

Jiao, Yu; Palmgren, Björn; Novozhilova, Ekaterina; Englund Johansson, Ulrica; Spieles-Engemann, Anne L.; Kale, Ajay; Stupp, Samuel I.; Olivius, Petri

2014-01-01

382

Simulation of stroke-related damage in cultured human nerve cells.  

Science.gov (United States)

We describe a novel cell culture protocol for the generation of neurons from a human teratocarcinoma cell line. These neurons were used to investigate hypoxic-ischaemic cell damage and for developing neuroprotective strategies. Cultures of human model neurons should eventually serve to reduce the number of experimental animals in cerebral stroke research. PMID:19835047

Bicker, Gerd; Gierse, Andrea; Tan, Saime; Paquet-Durand, François

2007-01-01

383

Nerve growth factor promotes TLR4 signaling-induced maturation of human dendritic cells in vitro through inducible p75NTR 1.  

Science.gov (United States)

Nerve growth factor (NGF) has been shown to play important roles in the differentiation, function, and survival of immune cells, contributing to immune responses and pathogenesis of autoimmune diseases. Dendritic cells (DCs) are a potent initiator for immune and inflammatory responses upon recognition of pathogens via Toll-like receptors (TLR). However, expression of NGF and its receptors on human monocyte-derived DCs (MoDCs) and the role of NGF in the response of DCs to TLR ligands remain to be investigated. In the present study, we demonstrate that there were weak expressions of NGF and no expression of NGF receptors p140(TrkA) and p75(NTR) on human immature MoDCs, however, the expression of NGF and p75(NTR) on MoDCs could be significantly up-regulated by LPS in a dose- and time-dependent manner. NGF could markedly promote LPS-induced expression of HLA-DR, CD40, CD80, CD83, CD86, CCR7, secretion of IL-12p40 and proinflammatory cytokines IL-1, IL-6, TNF-alpha, and the T cell-stimulating capacity of MoDCs, indicating that NGF can promote LPS-induced DC maturation. The promoting effect of NGF on LPS-induced MoDCs maturation could be completely abolished by pretreatment of MoDCs with p75(NTR) antagonist, suggesting that LPS-induced p75(NTR) mediates the effect. Furthermore, increased activation of the p38MAPK and NF-kappaB pathways has been shown to be responsible for the NGF-promoted DC maturation. Therefore, NGF facilitates TLR4 signaling-induced maturation of human DCs through LPS-up-regulated p75(NTR) via activation of p38 MAPK and NF-kappaB pathways, providing another mechanism for the involvement of NGF in the immune responses and pathogenesis of autoimmune diseases. PMID:17947706

Jiang, Yingming; Chen, Guoyou; Zhang, Yi; Lu, Lin; Liu, Shuxun; Cao, Xuetao

2007-11-01

384