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CEREBRAL NERVE CELL NEOGENESIS AGENT  

UK PubMed Central (United Kingdom)

Disclosed are: a novel substance having a cerebral nerve cell neogenesis effect and a cerebral nerve cell neogenesis agent which comprises the substance and is effective for the treatment and/or prevention of nerve diseases. Specifically disclosed is a cerebral nerve cell neogenesis agent comprising a plasmalogen as an active ingredient. Particularly, a cerebral nerve cell neogenesis agent comprising, as an active ingredient, a plasmalogen extracted from a biological tissue (preferably an avian tissue) that mainly contains ethanolamine plasmalogen and choline plasmalogen is preferred.

IFUKU MASATAKA; FUJINO TAKEHIKO; MAWATARI SHIROU; SUGIYAMA MASAAKI; KODAMA YOSHIROU; FUCHU HIDETAKA; YUNOKI KEITA

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Proteomics analyses of activated human optic nerve head lamina cribrosa cells following biomechanical strain.  

UK PubMed Central (United Kingdom)

PURPOSE: To determine protein regulation following activation of human, optic nerve head (ONH), lamina cribrosa (LC) cells in response to mechanical strain. METHODS: LC cells were isolated and grown from donor tissue in specific media at 37°C and 5% CO(2) humidified incubator. Cells were grown to confluence on collagen I-coated flexible-bottom culture plates, rinsed with Dulbecco's phosphate-buffered saline, and left for 24 hours in serum-free media. They were subjected to 3% or 12% cyclic equiaxial stretch for 2 or 24 hours using a commercial strain-unit system. Control cells were serum-deprived and incubated without stretch for 24 hours. Nano liquid chromatography-mass spectrometry analysis with isobaric tags for relative and absolute quantitation labeling was used to determine protein regulation. RESULTS: In all, 526 proteins were discovered at a 95% confidence limit. Analysis of associated pathways and functional annotation indicated that the LC cells reacted in vitro to mechanical strain by activating pathways involved in protein synthesis, cellular movement, cell-to-cell signaling, and inflammation. These pathways indicated consistent major protein hubs across all stretch/time conditions involving transforming growth factor-?1 (TGF?1), tumor necrosis factor (TNF), caspase-3 (CASP3), and tumor protein-p53 (p53). Among proteins of particular interest, also found in multiple stretch/time conditions, were bcl-2-associated athanogene 5 (BAG5), nucleolar protein 66 (NO66), and eukaryotic translation initiation factor 5A (eIF-5A). CONCLUSIONS: Pathway analysis identified major protein hubs (TGF?1, TNF, CASP3, p53) and pathways all previously implicated in cellular activation and in the pathogenesis of glaucomatous optic neuropathy. Several specific proteins of interest (BAG5, NO66, eIF-5A) were identified for future investigation as to their role in ONH glial activation.

Rogers R; Dharsee M; Ackloo S; Flanagan JG

2012-06-01

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

Directory of Open Access Journals (Sweden)

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

Tsuda Yoshifumi; Kanje Martin; Dahlin Lars B

2011-01-01

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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

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Glial cells activation potentially contributes to the upregulation of stromal cell-derived factor-1? after optic nerve crush in rats.  

UK PubMed Central (United Kingdom)

Stromal cell-derived factor-1? (SDF-1?) plays an important role after injury. However, little is known regarding its temporal and spatial expression patterns or how it interacts with glial cells after optic nerve crush injury. We characterized the temporal and spatial expression pattern of SDF-1? in the retina and optic nerve following optic nerve crush and demonstrated that SDF-1? is localized to the glial cells that are distributed in the retina and optic nerve. CXCR4, the receptor for SDF-1?, is expressed along the ganglion cell layer (GCL). The relative expression levels of Sdf-1? mRNA and SDF-1? protein in the retina and optic nerve 1, 2, 3, 5, 7, 10 and 14 days after injury were determined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, respectively, and the Cxcr4 mRNA expression was determined using real-time PCR. Immunofluorescence and immunohistochemical approaches were used to detect the localization of SDF-1? and CXCR4 after injury. The upregulation of Sdf-1? and Cxcr4 mRNA was detected as early as day one after injury in the retina and day two in the optic nerve, the expression peaks 5-7 days after injury. The expression of Sdf-1? and Cxcr4 mRNA was maintained for at least 14 days after the optic nerve crush injury. Furthermore, SDF-1?-positive zones were distributed locally in the reactive glial cells, which suggested potential autocrine stimulation. CXCR4 was mainly expressed in the GCL, which was also adjacent to the the glial cells. These findings suggest that following optic nerve crush, the levels of endogenous SDF-1? and CXCR4 increase in the retina and optic nerve, where activated glial cells may act as a source of increased SDF-1? protein.

Yang XT; Pan DC; Chen ET; Bi YY; Feng DF

2013-10-01

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Interaction of the sympathetic nerve with pancreatic cancer cells promotes perineural invasion through the activation of STAT3 signaling.  

UK PubMed Central (United Kingdom)

Perineural invasion (PNI) is one of the most important causes of local recurrence and poor survival in pancreatic cancer. However, the exact mechanism of PNI is still not clear. In this study, we sought to identify the reciprocal signaling interactions between sympathetic nerves and pancreatic cancer cells and the underlying mechanisms. We used mouse dorsal root ganglia and pancreatic cancer cells cocultured in vitro, cellular and molecular biology, and animal models to evaluate the function of the sympathetic neurotransmitter norepinephrine (NE) in PNI progression and pathogenesis. NE promoted PNI of pancreatic cancer cells and increased levels of phosphorylated STAT3 in a concentration-dependent manner. NE-mediated activation of STAT3 was inhibited by blocking ?-adrenergic receptors (AR) and by blocking protein kinase A, but not through blocking ?-AR. Blocking STAT3 could inhibit NE-induced NGF, MMP2, and MMP9 expression and attenuate the migratory, invasive ability and PNI of pancreatic cancer cells. Furthermore, PNI of pancreatic cancer cells was blocked by treatment with a STAT3 phosphorylation inhibitor in vivo. These studies show that NE plays a critical role in pancreatic cancer PNI development and progression through the ?-AR/PKA/STAT3 signaling pathway. Reciprocal signaling interactions between the sympathetic nerves and pancreatic cancer cells critically contribute to pancreatic cancer PNI pathogenesis. Inhibition of the activity of sympathetic nerves or STAT3 may be potential strategies for pancreatic cancer PNI therapy.

Guo K; Ma Q; Li J; Wang Z; Shan T; Li W; Xu Q; Xie K

2013-03-01

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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.

Undem Bradley J; Carr Michael J

2001-01-01

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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; Jovanovi? Svetlana

2011-01-01

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Activation of MAPK ERK in peripheral nerve after injury  

Directory of Open Access Journals (Sweden)

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

Agthong S; Kaewsema A; Tanomsridejchai N; Chentanez V

2006-01-01

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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

1990-01-01

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

Energy Technology Data Exchange (ETDEWEB)

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.

Holstein, T.W.; David, C.N. (Univ. of Munich (Germany, F.R.))

1990-12-01

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

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

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

2010-01-01

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Angiotensin type 2 receptors in the intermediolateral cell column of the spinal cord: Negative regulation of sympathetic nerve activity and blood pressure.  

UK PubMed Central (United Kingdom)

BACKGROUND: Our previous study demonstrated that AT2R in brainstem nuclei participated in the regulation of sympathetic outflow and cardiovascular function. However, the functional significance of AT2R in the intermediolateral cell column (IML) of the thoracic spinal cord in normal rats remains elusive. We hypothesized that AT2R activation in the IML exerts a sympatho-inhibitory effect. METHODS AND RESULTS: Using Western-blot analysis, immunohistochemical staining and quantitative real-time PCR, both AT1R and AT2R expressions were detected in the spinal cord. The highest AT2R protein expression was found in the IML, while AT1R expression didn't display regional differences within the gray matter. Microinjection of Ang II into the IML dose-dependently elevated mean blood pressure (MAP, employing a transducer-tipped catheter) and renal sympathetic nerve activity (RSNA, using a pair of platinum-iridium recording electrodes), which were completely abolished by Losartan, and attenuated by TEMPOL and apocynin. Activation of AT2R in the IML with CGP42112 evoked hypotension (?MAP: -21±4mmHg) and sympatho-inhibition (RSNA: 73±3% of baseline), which were completely abolished by PD123319 and l-NAME. Blockade of AT2R in the IML with PD123319 significantly increased MAP (11±1mmHg) and sympathetic nerve activity (RSNA: 133±13% of baseline). Moreover, PD123319 significantly enhanced the Ang II induced pressor response. Furthermore, in isolated IML neurons, CGP42112 treatment augmented potassium current and decreased resting membrane potential by employing whole-cell patch clamp. CONCLUSION: In the normal condition, AT2R in the IML tonically inhibits sympathetic activity through an NO/NOS dependent pathway and subsequent potassium channel activation.

Chao J; Gao J; Parbhu KJ; Gao L

2013-07-01

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Nerve injury-related autoimmunity activation leads to chronic inflammation and chronic neuropathic pain.  

UK PubMed Central (United Kingdom)

BACKGROUND: Peripheral nerve injuries that provoke neuropathic pain are associated with chronic inflammation and nervous lesions. The authors hypothesized that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury. METHODS: The authors observed chronic inflammation and neuropathic behaviors for up to 12 weeks after nerve injury in T lymphocyte-deficient nude mice and their heterozygous littermates. Lymphocyte proliferation and Schwann cell apoptosis were examined after coculture of each population with various neural tissues from normal rats and those with nerve injury. RESULT: Nude mice recovered faster and exhibited less thermal hyperalgesia after nerve injury compared to their heterozygous littermates. A large number of IL-17 cells indicative of lymphocyte activation were found in the injured sciatic nerve and spinal cord (L4-6) of heterozygous littermates, but far fewer of these populations were found in nude mice. In vitro lymphocyte proliferation was enhanced after coculture with nerve tissues from normal rats compared to nerve tissue-free phosphate-buffered saline controls. In particular, coculture with sciatic nerve tissue enhanced proliferation by 80%, dorsal root ganglion by 46%, and spinal cord by 14%. Moreover, neural tissues from rats with nerve injury markedly increased the lymphocyte proliferation compared to coculture with tissues from corresponding normal rats. Schwann cell apoptosis was triggered in vitro when cocultured with lymphocytes from neuropathic rats. CONCLUSION: Our study suggests that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury.

Li J; Wei GH; Huang H; Lan YP; Liu B; Liu H; Zhang W; Zuo YX

2013-02-01

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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.  

UK PubMed Central (United Kingdom)

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 (MWCNTs-Au) nanocomposites modified screen printed carbon electrode (SPCE), which is used for the immobilization of AChE specific antibody. 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 concentrations of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to OP 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 exposure to OPs.

Chen A; Du D; Lin Y

2012-02-01

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Behavioral evaluation of regenerated rat sciatic nerve by a nanofibrous PHBV conduit filled with Schwann cells as artificial nerve graft.  

UK PubMed Central (United Kingdom)

The aim of this study is to develop a nanofibrous polymeric nerve conduit with Schwann cells (SCs) and to evaluate its efficiency on the promotion of functional and locomotive activities in rats. The conduits were implanted into a 30-mm gap in the sciatic nerves of the rats. Four months after surgery, the rats were monitored and evaluated by behavioral analyses such as toe out angle, toe spreading analysis, walking track analysis, extensor postural thrust, open-field analysis, swimming test and nociceptive function, four months post surgery. Four months post-operatively, the results from behavioral analyses demonstrated that in the grafted groups especially in the grafted group with SCs, the rat sciatic nerve trunk had been reconstructed with functional recovery such as walking, swimming and recovery of nociceptive function. This study proves the feasibility of artificial conduit with SCs for nerve regeneration by bridging a longer defect in the rat model.

Biazar E; Heidari Keshel S; Pouya M

2013-09-01

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Factors influencing peripheral nerve stimulation produced inhibition of primate spinothalamic tract cells.  

UK PubMed Central (United Kingdom)

Several factors that influence the inhibition of primate spinothalamic tract (STT) cells produced by repetitive peripheral conditioning stimulation have been studied. Identified STT cells were recorded from the lumbosacral spinal cord in intact, anesthetized monkeys. In addition, presumed STT cells were recorded from unanesthetized, decerebrate or decerebrate, spinalized monkeys; these cells were identified by antidromic activation from the contralateral ventral lateral funiculus of the upper cervical spinal cord. Activity of the STT cells was evoked by electrically stimulating the sural nerve with pulses having an intensity strong enough to activate C fibers. The C fiber evoked STT cell activity was compared before, during and after repetitive conditioning stimuli applied to the tibial nerve for 5 min. By applying repetitive strengths of conditioning stimuli, it was found that the A delta fiber group is the most important for producing inhibition of STT cells, although significant additional effects were also produced by the A alpha beta and C fiber groups. Conditioning stimuli with fixed intensity at different frequencies showed that the higher the frequency the more powerful the inhibition within the range we tested (0.5-20 Hz). The inhibition produced by peripheral nerve stimulation was segmentally organized, so the most effective nerve in producing inhibition amongst those tested was the ipsilateral tibial nerve. The contralateral sciatic nerve, the ipsilateral median nerve and the contralateral median nerve were less effective in that order. The results of the present experiments suggest that the most effective way to produce analgesia by peripheral nerve stimulation would be by high frequency stimulation of a nerve innervating the area from which pain originates with an intensity at least strong enough to activate A delta fibers.

Chung JM; Lee KH; Hori Y; Endo K; Willis WD

1984-07-01

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Structure-activity relationship of nerve-highlighting fluorophores.  

Science.gov (United States)

Nerve damage is a major morbidity associated with numerous surgical interventions. Yet, nerve visualization continues to challenge even the most experienced surgeons. A nerve-specific fluorescent contrast agent, especially one with near-infrared (NIR) absorption and emission, would be of immediate benefit to patients and surgeons. Currently, there are only three classes of small molecule organic fluorophores that penetrate the blood nerve barrier and bind to nerve tissue when administered systemically. Of these three classes, the distyrylbenzenes (DSBs) are particularly attractive for further study. Although not presently in the NIR range, DSB fluorophores highlight all nerve tissue in mice, rats, and pigs after intravenous administration. The purpose of the current study was to define the pharmacophore responsible for nerve-specific uptake and retention, which would enable future molecules to be optimized for NIR optical properties. Structural analogs of the DSB class of small molecules were synthesized using combinatorial solid phase synthesis and commercially available building blocks, which yielded more than 200 unique DSB fluorophores. The nerve-specific properties of all DSB analogs were quantified using an ex vivo nerve-specific fluorescence assay on pig and human sciatic nerve. Results were used to perform quantitative structure-activity relationship (QSAR) modeling and to define the nerve-specific pharmacophore. All DSB analogs with positive ex vivo fluorescence were tested for in vivo nerve specificity in mice to assess the effect of biodistribution and clearance on nerve fluorescence signal. Two new DSB fluorophores with the highest nerve to muscle ratio were tested in pigs to confirm scalability. PMID:24039960

Gibbs, Summer L; Xie, Yang; Goodwill, Haley L; Nasr, Khaled A; Ashitate, Yoshitomo; Madigan, Victoria J; Siclovan, Tiberiu M; Zavodszky, Maria; Tan Hehir, Cristina A; Frangioni, John V

2013-09-09

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Structure-activity relationship of nerve-highlighting fluorophores.  

UK PubMed Central (United Kingdom)

Nerve damage is a major morbidity associated with numerous surgical interventions. Yet, nerve visualization continues to challenge even the most experienced surgeons. A nerve-specific fluorescent contrast agent, especially one with near-infrared (NIR) absorption and emission, would be of immediate benefit to patients and surgeons. Currently, there are only three classes of small molecule organic fluorophores that penetrate the blood nerve barrier and bind to nerve tissue when administered systemically. Of these three classes, the distyrylbenzenes (DSBs) are particularly attractive for further study. Although not presently in the NIR range, DSB fluorophores highlight all nerve tissue in mice, rats, and pigs after intravenous administration. The purpose of the current study was to define the pharmacophore responsible for nerve-specific uptake and retention, which would enable future molecules to be optimized for NIR optical properties. Structural analogs of the DSB class of small molecules were synthesized using combinatorial solid phase synthesis and commercially available building blocks, which yielded more than 200 unique DSB fluorophores. The nerve-specific properties of all DSB analogs were quantified using an ex vivo nerve-specific fluorescence assay on pig and human sciatic nerve. Results were used to perform quantitative structure-activity relationship (QSAR) modeling and to define the nerve-specific pharmacophore. All DSB analogs with positive ex vivo fluorescence were tested for in vivo nerve specificity in mice to assess the effect of biodistribution and clearance on nerve fluorescence signal. Two new DSB fluorophores with the highest nerve to muscle ratio were tested in pigs to confirm scalability.

Gibbs SL; Xie Y; Goodwill HL; Nasr KA; Ashitate Y; Madigan VJ; Siclovan TM; Zavodszky M; Tan Hehir CA; Frangioni JV

2013-01-01

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

Science.gov (United States)

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

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

2013-10-01

 
 
 
 
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Studies on nerve cell affinity of chitosan-derived materials.  

UK PubMed Central (United Kingdom)

Reparation of the central nervous system (CNS) is important because when it is impaired its recovery is difficult and concomitant malfunction of other parts of body occurs. In our previous studies, chitosan was found to be a good material supporting nerve repair. The purpose of this article was to study the ability of chitosan and some chitosan-derived materials to facilitate the growth of nerve cells. Those materials were chitosan, glutaraldehyde-crosslinked chitosan, glutaraldehyde-crosslinked chitosan-gelatin conjugate, a chitosan-gelatin mixture, chitosan coated with polylysine (CAP), and a chitosan-polylysine mixture (CPL). Gelatin and polylysine were used as controls. After nerve cells (gliosarcoma cells and normal cerebral cells) were grown on those materials, their attachment, spread, and growth were observed. The adsorption of some extracellular matrix molecules such as laminin and fibronectin on the materials and the role the molecules play in nerve cell attachment and spreading were also studied by enzyme-linked immunosorbent assay and MTT method. We found that both CAP and CPL have excellent nerve cell affinity, defined as the ability to promote nerve cell to grow and function normally. Those two materials may be promising for the repair of the nervous system. Materials precoated with laminin, fibronectin, and serum were analyzed for their nerve cell affinity. Results suggest that after being precoated with laminin and fibronectin solution or serum, all material have better nerve cell affinity.

Haipeng G; Yinghui Z; Jianchun L; Yandao G; Nanming Z; Xiufang Z

2000-11-01

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Adipose-derived stem cells promote peripheral nerve repair  

Science.gov (United States)

Introduction Recent evidence suggests that the implantation of bone marrow-derived mesenchymal stem cells improves peripheral nerve regeneration. In this study we aimed to investigate whether adipose-derived stem cells (ADSCs) can be used for peripheral nerve repair. Material and methods In a rat model, nerve regeneration was evaluated across a 15 mm lesion in the sciatic nerve by using an acellular nerve injected with allogenic ADSCs. The walking behaviour of rats was measured by footprint analysis, and electrophysiological analysis and histological examination were performed to evaluate the efficacy of nerve regeneration. Results Cultured ADSCs became morphologically homogeneous with a bipolar, spindle-like shape after ex vivo expansion. Implantation of ADSCs into the rat models led to (i) improved walking behaviour as measured by footprint analysis, (ii) increased conservation of muscle-mass ratio of gastrocnemius and soleus muscles, (iii) increased nerve conduction velocity, and (iv) increased number of myelinated fibres within the graft. Conclusions Adipose-derived stem cells could promote peripheral nerve repair in a rat model. Although the detailed mechanism by which ADSCs promote peripheral nerve regeneration is being investigated in our lab, our results suggest that ADSCs transplantation represents a powerful therapeutic approach for peripheral nerve injury.

Liu, Gui-Bo; Cheng, Yong-Xia; Feng, Yu-Kuan; Pang, Chao-Jian; Li, Qi; Wang, Ying; Jia, Hua; Tong, Xiao-Jie

2011-01-01

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Segmentation of the retinal optic nerve head using Hough transform and active contour models  

Directory of Open Access Journals (Sweden)

Full Text Available Optic nerve head is part of the retina where ganglion cell axons exit the eye to form the optic nerve. Glaucomatous changes related to loss of the nerve fibers decrease the neuroretinal rim and expand the area and volume of the cup. This study implements the detection of the optic nerve head in retinal fundus images based on the Hough Transform and Active Contour Models.The process starts with the image enhancement using homomorphic filtering for illumination correction, then proceeds with the removal of blood vessels on the image to facilitate the subsequent segmentation process.The result of the Hough Transform fitting circle becomes the initial level set for the active contour model. The experimental results show that the implemented segmentation algorithms are capable of segmenting optic nerve head with the average accuracy of 75.56%.

Handayani Tjandrasa; Ari Wijayanti; Nanik Suciati

2012-01-01

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Segmentation of the retinal optic nerve head using Hough transform and active contour models  

Directory of Open Access Journals (Sweden)

Full Text Available Optic nerve head is part of the retina where ganglion cell axons exit the eye to form the optic nerve. Glaucomatous changes related to loss of the nerve fibers decrease the neuroretinal rim and expand the area and volume of the cup. This study implements  the detection of the optic nerve head in retinal fundus images based on the Hough Transform and Active Contour Models. The process starts with the image enhancement using homomorphic filtering for illumination correction, then proceeds with the removal of blood vessels on the image  to facilitate the subsequent segmentation process. The result of the Hough Transform fitting circle becomes the initial level set for the active contour model. The experimental results show that the implemented segmentation algorithms are capable of segmenting optic nerve head with the average accuracy of 75.56%. 

Handayani Tjandrasa; Ari Wijayanti; Nanik Suciati

2012-01-01

25

STEREOLOGIC ANALYSIS OF VASCULAR NET AND NERVE CELLS OF GENERAL SOMATOMOTOR NUCLEI OF CRANIAL NERVES  

Directory of Open Access Journals (Sweden)

Full Text Available The analysis was done on 10 samples of general somatomotor nuclei (GSN) of cranial nerves located in the brain stem, which were colored by the Mallory method. The research was conducted by standard testing system A 100 with the use of the light microscope and 40 x zoom objective. We determined the volume density of vascular net and nerve cells of investigated structures. The obtained values were mutually compared. GSN located in mesencephalon were more significantly vascularized. A part of the oculomotorius nuclei, made of nerve cells, is significantly larger compared with other GSN. The oculomotorius nuclei have equal number of nerve cells and blood vessels, while the number of blood vessels in the other GSN is a significantly larger.

Zdenka Krivokuca; Tatjana Bucma; Vesna Gajanin; Igor Sladojevic

2006-01-01

26

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)

[en] 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

1997-01-01

27

Endoplasmic reticulum calcium signaling in nerve cells  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english The endoplasmic reticulum (ER) is an important organelle involved in various types of signaling in nerve cells. The ER serves as a dynamic Ca2+ pool being thus involved in rapid signaling events associated with cell stimulation by either electrical (action potential) or chemical (neurotransmitters) signals. This function is supported by Ca2+ release channels (InsP3 and ryanodine receptors) and SERCA Ca2+ pumps residing in the endomembrane. In addition the ER provides a sp (more) ecific environment for the posttranslational protein processing and transport of various molecules towards their final destination. In parallel, the ER acts as a "calcium tunnel," which facilitates Ca2+ movements within the cell by avoiding cytoplasmic routes. Finally the ER appears as a source of numerous signals aimed at the nucleus and involved in long-lasting adaptive cellular responses. All these important functions are controlled by intra-ER free Ca2+ which integrates various signaling events and establishes a link between fast signaling, associated with ER Ca2+ release/uptake, and long-lasting adaptive responses relying primarily on the regulation of protein synthesis. Disruption of ER Ca2+ homeostasis triggers several forms of cellular stress response and is intimately involved in neurodegeneration and neuronal cell death

VERKHRATSKY, ALEXEI

2004-01-01

28

Endothelin in the control of renal sympathetic nerve activity.  

Science.gov (United States)

The kidney is densely innervated by sympathetic nerves. Increases in renal sympathetic nerve activity (RSNA) decrease urinary sodium excretion. The kidney also has abundant afferent sensory innervation, located primarily in the renal pelvic wall. Sympathetic nerve fibers and afferent nerve fibers often run separately but intertwined in the same nerve bundles in the renal pelvic wall, providing anatomic support for a functional interaction between RSNA and afferent renal nerve activity (ARNA). Activation of RSNA increases ARNA, which in turn decreases RSNA by activation of the renorenal reflexes. Thus, RSNA-induced increases in ARNA exert a powerful negative feedback control of RSNA via activation of the renorenal reflexes in the overall goal of maintaining low RSNA to facilitate urinary sodium excretion. A high-sodium diet enhances and a low-sodium diet reduces the RSNA-induced increases in ARNA. The physiologic importance of the dietary-induced changes in the RSNA-mediated increases in ARNA is underlined by salt-sensitive hypertension in rats lacking afferent renal innervation. Endothelin (ET), ET(A) receptors (R), and ET(B)-R are present in the renal pelvic wall. ET plays a modulatory role in the activation of the afferent renal nerves that is dependent on dietary sodium intake. In a high-sodium diet, increased activation of ET(B)-R facilitates the interaction between RSNA and ARNA resulting in suppression of RSNA, via activation of the renorenal reflexes, to limit sodium retention. In a low-sodium diet, increased activation of renal pelvic ET(A)-R suppresses the interaction between RSNA and ARNA which increases RSNA via impairment of the renorenal reflex mechanism, eventually leading to sodium retention. These findings suggest that the increased renal sympathetic nerve activity and salt-sensitive hypertension in ET-1/ET(B)-R-deficient subjects is, at least in part, related to suppressed interaction between RSNA and ARNA. PMID:21893993

Kopp, Ulla C

2011-08-30

29

Endothelin in the control of renal sympathetic nerve activity.  

UK PubMed Central (United Kingdom)

The kidney is densely innervated by sympathetic nerves. Increases in renal sympathetic nerve activity (RSNA) decrease urinary sodium excretion. The kidney also has abundant afferent sensory innervation, located primarily in the renal pelvic wall. Sympathetic nerve fibers and afferent nerve fibers often run separately but intertwined in the same nerve bundles in the renal pelvic wall, providing anatomic support for a functional interaction between RSNA and afferent renal nerve activity (ARNA). Activation of RSNA increases ARNA, which in turn decreases RSNA by activation of the renorenal reflexes. Thus, RSNA-induced increases in ARNA exert a powerful negative feedback control of RSNA via activation of the renorenal reflexes in the overall goal of maintaining low RSNA to facilitate urinary sodium excretion. A high-sodium diet enhances and a low-sodium diet reduces the RSNA-induced increases in ARNA. The physiologic importance of the dietary-induced changes in the RSNA-mediated increases in ARNA is underlined by salt-sensitive hypertension in rats lacking afferent renal innervation. Endothelin (ET), ET(A) receptors (R), and ET(B)-R are present in the renal pelvic wall. ET plays a modulatory role in the activation of the afferent renal nerves that is dependent on dietary sodium intake. In a high-sodium diet, increased activation of ET(B)-R facilitates the interaction between RSNA and ARNA resulting in suppression of RSNA, via activation of the renorenal reflexes, to limit sodium retention. In a low-sodium diet, increased activation of renal pelvic ET(A)-R suppresses the interaction between RSNA and ARNA which increases RSNA via impairment of the renorenal reflex mechanism, eventually leading to sodium retention. These findings suggest that the increased renal sympathetic nerve activity and salt-sensitive hypertension in ET-1/ET(B)-R-deficient subjects is, at least in part, related to suppressed interaction between RSNA and ARNA.

Kopp UC

2011-01-01

30

Optical inhibition of motor nerve and muscle activity in vivo.  

UK PubMed Central (United Kingdom)

INTRODUCTION: There is no therapeutic approach that provides precise and rapidly reversible inhibition of motor nerve and muscle activity for treatment of spastic hypertonia. METHODS: We used optogenetics to demonstrate precise and rapidly reversible light-mediated inhibition of motor nerve and muscle activity in vivo in transgenic Thy1::eNpHR2.0 mice. RESULTS: We found optical inhibition of motor nerve and muscle activity to be effective at all muscle force amplitudes and determined that muscle activity can be modulated by changing light pulse duration and light power density. CONCLUSIONS: This demonstration of optical inhibition of motor nerves is an important advancement toward novel optogenetics-based therapies for spastic hypertonia.

Liske H; Towne C; Anikeeva P; Zhao S; Feng G; Deisseroth K; Delp S

2013-06-01

31

Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats.  

UK PubMed Central (United Kingdom)

We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague-Dawley rats were divided into the following four groups: (1) normal control group (NCG; n?=?8), (2) normal exercise group (NEG; n?=?8), (3) diabetes control group (DCG; n?=?8), and (4) diabetes exercise group (DEG; n?=?8). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5). Rats were subjected to treadmill exercise 5 days a week for 6 weeks. The protein level of NGF significantly increased in the NEG and DEG (p?activation in order to suppress apoptotic cell death in the soleus muscle of diabetic rats.

Chae CH; Jung SL; An SH; Jung CK; Nam SN; Kim HT

2011-06-01

32

Taste cell responses in the frog are modulated by parasympathetic efferent nerve fibers.  

Science.gov (United States)

We studied the anatomical properties of parasympathetic postganglionic neurons in the frog tongue and their modulatory effects on taste cell responses. Most of the parasympathetic ganglion cell bodies in the tongue were found in extremely small nerve bundles running near the fungiform papillae, which originate from the lingual branches of the glossopharyngeal (GP) nerve. The density of parasympathetic postganglionic neurons in the tongue was 8000-11,000/mm(3) of the extremely small nerve bundle. The mean major axis of parasympathetic ganglion cell bodies was 21 microm, and the mean length of parasympathetic postganglionic neurons was 1.45 mm. Electrical stimulation at 30 Hz of either the GP nerve or the papillary nerve produced slow hyperpolarizing potentials (HPs) in taste cells. After nicotinic acetyl choline receptors on the parasympathetic ganglion cells in the tongue had been blocked by intravenous (i.v.) injection of D-tubocurarine (1 mg/kg), stimulation of the GP nerve did not induce any slow HPs in taste cells but that of the papillary nerve did. A further i.v. injection of a substance P NK-1 antagonist, L-703,606, blocked the slow HPs induced by the papillary nerve stimulation. This suggests that the parasympathetic postganglionic efferent fibers innervate taste cells and are related to a generation of the slow HPs and that substance P is released from the parasympathetic postganglionic axon terminals. When the resting membrane potential of a taste cell was hyperpolarized by a prolonged slow HP, the gustatory receptor potentials for NaCl and sugar stimuli were enhanced in amplitude, but those for quinine-HCl and acetic acid stimuli remained unchanged. It is concluded that frog taste cell responses are modulated by activities of parasympathetic postganglionic efferent fibers innervating these cells. PMID:16243966

Sato, Toshihide; Okada, Yukio; Miyazaki, Toshihiro; Kato, Yuzo; Toda, Kazuo

2005-10-21

33

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.

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

2013-01-01

34

Bilateral peripheral neural activity observed in vivo following unilateral nerve injury.  

UK PubMed Central (United Kingdom)

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.

Behera D; Behera S; Jacobs KE; Biswal S

2013-01-01

35

Activation of the neuregulin-1/ErbB signaling pathway promotes the proliferation of neoplastic Schwann cells in human malignant peripheral nerve sheath tumors.  

UK PubMed Central (United Kingdom)

Patients with neurofibromatosis type 1 develop aggressive Schwann cell neoplasms known as malignant peripheral nerve sheath tumors (MPNSTs). Although tumor suppressor gene mutations play an important role in MPNST pathogenesis, it is likely that dysregulated signaling by as yet unidentified growth factors also contributes to the formation of these sarcomas. To test the hypothesis that neuregulin-1 (NRG-1) growth factors promote mitogenesis in MPNSTs, we examined the expression and action of NRG-1 in human MPNSTs and neurofibromas, the benign precursor lesions from which MPNSTs arise. Multiple alpha and beta transmembrane precursors from the class II and III NRG-1 subfamilies are present in both tumor types. Neoplastic Schwann cells within these neoplasms variably express the erbB kinases mediating NRG-1 responses (erbB2, erbB3 and/or erbB4). Human MPNST cell lines (Mash-1, YST-1, NMS-2 and NMS-2PC cells) similarly coexpress multiple NRG-1 isoforms and erbB receptors. These MPNST lines are NRG-1 responsive and demonstrate constitutive erbB phosphorylation. Treatment with PD168393 and PD158780, two structurally and mechanistically distinct erbB inhibitors, abolishes erbB phosphorylation and reduces DNA synthesis in these lines. These findings suggest that autocrine and/or paracrine NRG-1/erbB signaling promotes neoplastic Schwann cell proliferation and may be an important therapeutic target in neurofibromas and MPNSTs.

Stonecypher MS; Byer SJ; Grizzle WE; Carroll SL

2005-08-01

36

Activation of the neuregulin-1/ErbB signaling pathway promotes the proliferation of neoplastic Schwann cells in human malignant peripheral nerve sheath tumors.  

Science.gov (United States)

Patients with neurofibromatosis type 1 develop aggressive Schwann cell neoplasms known as malignant peripheral nerve sheath tumors (MPNSTs). Although tumor suppressor gene mutations play an important role in MPNST pathogenesis, it is likely that dysregulated signaling by as yet unidentified growth factors also contributes to the formation of these sarcomas. To test the hypothesis that neuregulin-1 (NRG-1) growth factors promote mitogenesis in MPNSTs, we examined the expression and action of NRG-1 in human MPNSTs and neurofibromas, the benign precursor lesions from which MPNSTs arise. Multiple alpha and beta transmembrane precursors from the class II and III NRG-1 subfamilies are present in both tumor types. Neoplastic Schwann cells within these neoplasms variably express the erbB kinases mediating NRG-1 responses (erbB2, erbB3 and/or erbB4). Human MPNST cell lines (Mash-1, YST-1, NMS-2 and NMS-2PC cells) similarly coexpress multiple NRG-1 isoforms and erbB receptors. These MPNST lines are NRG-1 responsive and demonstrate constitutive erbB phosphorylation. Treatment with PD168393 and PD158780, two structurally and mechanistically distinct erbB inhibitors, abolishes erbB phosphorylation and reduces DNA synthesis in these lines. These findings suggest that autocrine and/or paracrine NRG-1/erbB signaling promotes neoplastic Schwann cell proliferation and may be an important therapeutic target in neurofibromas and MPNSTs. PMID:15897877

Stonecypher, Mark S; Byer, Stephanie J; Grizzle, William E; Carroll, Steven L

2005-08-25

37

Substance P plays an important role in cell adhesion molecule 1-mediated nerve-pancreatic islet ? cell interaction.  

UK PubMed Central (United Kingdom)

Autonomic neurons innervate pancreatic islets of Langerhans and maintain blood glucose homeostasis by regulating hormone levels. We previously showed that cell adhesion molecule 1 (CADM1) mediated the attachment and interaction between nerves and aggregated pancreatic islet ? cells. In this study, we cocultured ?TC6 cells, a murine ? cell line, with mouse superior cervical ganglion (SCG) neurons. The oscillation of intracellular Ca(2+) concentration ([Ca(2+)]i) was observed in 27% and 14% of ?TC6 and CADM1-knockdown ?TC6 cells (?TC6(siRNA-CADM1) cells) in aggregates, respectively, within 1min after specific SCG nerve stimulation with scorpion venom. In ?TC6(siRNA-CADM1) cells, the responding rate during 3min after SCG nerve stimulation significantly increased compared with that within 1min, whereas the increase in the responding rate was not significantly different in ?TC6 cells. This indicated that the response of ?TC6 cells according to nerve stimulation occurred more rapidly and effectively than that of ?TC6(siRNA-CADM1) cells, suggesting CADM1 involvement in promoting the interaction between nerves and ? cells and among ? cells. In addition, because we found that neurokinin (NK)-1 receptors, which are neuropeptide substance P receptors, were expressed to a similar extent by both cells, we investigated the effect of substance P on nerve-? cell interaction. Pretreatment with CP99,994 (0.1?g/ml), an NK-1 receptor antagonist, reduced the responding rate of both cells, suggesting that substance P released from stimulated neurites was a mediator to activate ?TC6 cells. In addition, ? cells that were attached to neurites in a CADM1-mediated manner appeared to respond effectively to neurite activation via substance P/NK-1 receptors.

Nakamura M; Inoh Y; Nakanishi M; Furuno T

2013-08-01

38

Nerve Growth Factor in Cancer Cell Death and Survival  

Directory of Open Access Journals (Sweden)

Full Text Available One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.

Niamh H. Molloy; Danielle E. Read; Adrienne M. Gorman

2011-01-01

39

Malignant granular cell tumour of the sciatic nerve  

International Nuclear Information System (INIS)

A case of malignant granular cell tumour of the sciatic nerve is presented. Computed tomography demonstrated isodensity with muscle and minimal enhancement. Magnetic resonance demonstrated T1 isointensity with muscle with marked enhancement, and isointensity with fat on proton and T2 images. Pathological evidence is presented for its probable Schwann cell histogenesis. 9 refs., 3 figs.

1995-01-01

40

Malignant granular cell tumour of the sciatic nerve  

Energy Technology Data Exchange (ETDEWEB)

A case of malignant granular cell tumour of the sciatic nerve is presented. Computed tomography demonstrated isodensity with muscle and minimal enhancement. Magnetic resonance demonstrated T1 isointensity with muscle with marked enhancement, and isointensity with fat on proton and T2 images. Pathological evidence is presented for its probable Schwann cell histogenesis. 9 refs., 3 figs.

Hurrell, M.A.; McLean, C.; Desmond, P.; Tress, B.M.; Kaye, A. [Royal Melbourne Hospital, Parkville, VIC (Australia)

1995-05-01

 
 
 
 
41

Nerve Growth Factor in Cancer Cell Death and Survival  

Science.gov (United States)

One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.

Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M.

2011-01-01

42

Estradiol promotes neural stem cell differentiation into endothelial lineage and angiogenesis in injured peripheral nerve.  

UK PubMed Central (United Kingdom)

Neural stem cells (NSCs) differentiate into endothelial cells (ECs) and neuronal cells. Estradiol (E2) is known to exhibit proangiogenic effects on ischemic tissues via EC activation. Therefore, we hypothesized that E2 can promote the therapeutic potential of NSC transplantation for injured nerve repair via the differentiation of NSCs into ECs during neovascularization. NSCs isolated from newborn mouse brains were transplanted into injured sciatic nerves with (NSC/E2 group) or without E2-conjugated gelatin hydrogel (E2 group). The NSC/E2 group exhibited the greatest recovery in motor nerve conduction velocity, voltage amplitude, and exercise tolerance. Histological analyses revealed increased intraneural vascularity and blood perfusion as well as striking NSC recruitment to the neovasculature in the injured nerves in the NSC/E2 group. In vitro, E2 enhanced the NSC migration and proliferation inhibiting apoptosis. Fluorescence-activated cell sorting analysis also revealed that E2 significantly increased the percentage of CD31 in NSCs, and the effect of E2 was completely neutralized by the estrogen receptor antagonist ICI. The combination of E2 administration and NSC transplantation cooperatively improved the functional recovery of injured peripheral nerves, at least in part, via E2-associated NSC differentiation into ECs. These findings provide a novel mechanistic insight into both NSC biology and the biological effects of endogenous E2.

Sekiguchi H; Ii M; Jujo K; Thorne T; Ito A; Klyachko E; Hamada H; Kessler JA; Tabata Y; Kawana M; Asahi M; Hagiwara N; Losordo DW

2013-01-01

43

Effects of tissue glues on electrical activity in isolated nerve.  

UK PubMed Central (United Kingdom)

The effect of tissue glues--Tissucol and Histoacryl--on the action potentials in isolated frog nerve was studied by means of a single gap arrangement. Tissucol injected into the gap increased the action potential amplitude, whereas Histoacryl abolished the electrical activity. This glue-gap method can be applied in tests with new tissue glues.

W?odarczyk J

1991-01-01

44

Synergistic effects of ultrashort wave and bone marrow stromal cells on nerve regeneration with acellular nerve allografts.  

UK PubMed Central (United Kingdom)

Acellular nerve allografts (ANA) possess bioactivity and neurite promoting factors in nerve tissue engineering. Previously we reported that low dose ultrashort wave (USW) radiation could enhance the rate and quality of peripheral nerve regeneration with ANA repairing sciatic nerve defects. Meanwhile, ANA implanted with bone marrow stromal cells (BMSCs) exhibited a similar result. Thus, it is interesting to know whether it might yield a synergistic effect when USW radiation is combined with BMSCs-laden ANA. Here we investigated the effectiveness of ANA seeded with BMSCs, combined with USW therapy on repairing peripheral nerve injuries. Adult male Wistar rats were randomly divided into four groups: Dulbecco's modified Eagle's medium (DMEM) control group, BMSCs-laden group, ultrashort wave (USW) group and BMSC + USW group. The regenerated nerves were assayed morphologically and functionally, and growth-promoting factors in the regenerated tissues following USW administration or BMSCs integration were also detected. The results indicated that the combination therapy caused much better beneficial effects evidenced by increased myelinated nerve fiber number, myelin sheath thickness, axon diameter, sciatic function index, nerve conduction velocity, and restoration rate of tibialis anterior wet weight. Moreover, the mRNA levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the spinal cord and muscles were elevated significantly. In conclusion, we found a synergistic effect of USW radiation and BMSCs treatment on peripheral nerve regeneration, which may help establish novel strategies for repairing peripheral nerve defects. Synapse 67:637-647, 2013. © 2013 Wiley Periodicals, Inc.

Pang CJ; Tong L; Ji LL; Wang ZY; Zhang X; Gao H; Jia H; Zhang LX; Tong XJ

2013-10-01

45

Synergistic effects of ultrashort wave and bone marrow stromal cells on nerve regeneration with acellular nerve allografts.  

Science.gov (United States)

Acellular nerve allografts (ANA) possess bioactivity and neurite promoting factors in nerve tissue engineering. Previously we reported that low dose ultrashort wave (USW) radiation could enhance the rate and quality of peripheral nerve regeneration with ANA repairing sciatic nerve defects. Meanwhile, ANA implanted with bone marrow stromal cells (BMSCs) exhibited a similar result. Thus, it is interesting to know whether it might yield a synergistic effect when USW radiation is combined with BMSCs-laden ANA. Here we investigated the effectiveness of ANA seeded with BMSCs, combined with USW therapy on repairing peripheral nerve injuries. Adult male Wistar rats were randomly divided into four groups: Dulbecco's modified Eagle's medium (DMEM) control group, BMSCs-laden group, ultrashort wave (USW) group and BMSC + USW group. The regenerated nerves were assayed morphologically and functionally, and growth-promoting factors in the regenerated tissues following USW administration or BMSCs integration were also detected. The results indicated that the combination therapy caused much better beneficial effects evidenced by increased myelinated nerve fiber number, myelin sheath thickness, axon diameter, sciatic function index, nerve conduction velocity, and restoration rate of tibialis anterior wet weight. Moreover, the mRNA levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the spinal cord and muscles were elevated significantly. In conclusion, we found a synergistic effect of USW radiation and BMSCs treatment on peripheral nerve regeneration, which may help establish novel strategies for repairing peripheral nerve defects. Synapse 67:637-647, 2013. © 2013 Wiley Periodicals, Inc. PMID:23554017

Pang, Chao-Jian; Tong, Lei; Ji, Li-Li; Wang, Zhen-Yu; Zhang, Xu; Gao, Hai; Jia, Hua; Zhang, Li-Xin; Tong, Xiao-Jie

2013-05-02

46

SiRNA Delivery into Mammalian Nerve Cells.  

Science.gov (United States)

The present invention relates to methods of affecting expression of a target gene, suitably brain-derived neurotrophic factor (BDNF) or related genes in a nerve cell in the central nervous system of a mammal. The method includes formulating and delivering...

G. S. Mitchell T. L. Baker-Harman

2004-01-01

47

Tissue engineering the retinal ganglion cell nerve fiber layer.  

Science.gov (United States)

Retinal degenerative diseases, such as glaucoma and macular degeneration, affect millions of people worldwide and ultimately lead to retinal cell death and blindness. Cell transplantation therapies for photoreceptors demonstrate integration and restoration of function, but transplantation into the ganglion cell layer is more complex, requiring guidance of axons from transplanted cells to the optic nerve head in order to reach targets in the brain. Here we create a biodegradable electrospun (ES) scaffold designed to direct the growth of retinal ganglion cell (RGC) axons radially, mimicking axon orientation in the retina. Using this scaffold we observed an increase in RGC survival and no significant change in their electrophysiological properties. When analyzed for alignment, 81% of RGCs were observed to project axons radially along the scaffold fibers, with no difference in alignment compared to the nerve fiber layer of retinal explants. When transplanted onto retinal explants, RGCs on ES scaffolds followed the radial pattern of the host retinal nerve fibers, whereas RGCs transplanted directly grew axons in a random pattern. Thus, the use of this scaffold as a cell delivery device represents a significant step towards the use of cell transplant therapies for the treatment of glaucoma and other retinal degenerative diseases. PMID:23489919

Kador, Karl E; Montero, Ramon B; Venugopalan, Praseeda; Hertz, Jonathan; Zindell, Allison N; Valenzuela, Daniel A; Uddin, Mohammed S; Lavik, Erin B; Muller, Kenneth J; Andreopoulos, Fotios M; Goldberg, Jeffrey L

2013-03-11

48

Ultrastructure of perineurial cells during peripheral nerve regeneration. Electron microscopical investigations on the so-called amputation neuroma.  

UK PubMed Central (United Kingdom)

The ultrastructural morphology of perineurial cells was examined after transsection of the sciatic nerve of rats. The material prepared for investigation was taken from the proximal nerve stump and the so-called amputation neuroma at different times after operation. We found that perineurial cells begin to activate in the first week, and in the further course of regeneration they modulate their cytoplasmic structure corresponding to the function of proliferation or synthesis. Besides the reconstitution of a diffusion barrier the perineurial cells may exert a stabilizing function in regenerating nerve tissue comparable to myofibroblasts in granulation tissue, and may be engaged in remodeling of connective tissue fibers. The relations of perineurial cells to other cells of peripheral nerves under the condition of regeneration are discussed.

Katenkamp D; Stiller D

1978-01-01

49

Ultrastructure of perineurial cells during peripheral nerve regeneration. Electron microscopical investigations on the so-called amputation neuroma.  

Science.gov (United States)

The ultrastructural morphology of perineurial cells was examined after transsection of the sciatic nerve of rats. The material prepared for investigation was taken from the proximal nerve stump and the so-called amputation neuroma at different times after operation. We found that perineurial cells begin to activate in the first week, and in the further course of regeneration they modulate their cytoplasmic structure corresponding to the function of proliferation or synthesis. Besides the reconstitution of a diffusion barrier the perineurial cells may exert a stabilizing function in regenerating nerve tissue comparable to myofibroblasts in granulation tissue, and may be engaged in remodeling of connective tissue fibers. The relations of perineurial cells to other cells of peripheral nerves under the condition of regeneration are discussed. PMID:720451

Katenkamp, D; Stiller, D

1978-01-01

50

[11C]PK11195 PET imaging of spinal glial activation after nerve injury in rats.  

UK PubMed Central (United Kingdom)

The role of glial activation has been implicated in the development and persistence of neuropathic pain after nerve injury by recent studies. PK11195 binding to the translocator protein 18kDa (TSPO) has been shown to be enhanced in activated microglia. This study was designed to assess PK11195 imaging in spinal microglia during activation after nerve injury. The development of neuropathic pain was induced by partial sciatic nerve ligation (PSL). PSL rats on days 7 and 14 after nerve injury were subjected to imaging with a small-animal positron emission tomography/computed tomography (PET/CT) scanner using [(11)C]PK11195 to detect spinal microglial activation by means of noninvasive in vivo imaging. Spinal [(3)H]PK11195 autoradiography was performed to confirm the results of [(11)C]PK11195 PET in PSL rats. Quantitative RT-PCR of CD11b and GFAP mRNA, and the immunohistochemistry of Iba1 and GFAP were investigated to detect activated microglia and astrocytes. Mechanical allodynia was observed in the ipsilateral paw of PSL rats from day 3 after nerve injury and stably persisted from days 7 to 14. PET/CT fusion images clearly showed large amounts of accumulation of [(11)C]PK11195 in the lumbar spinal cord on days 7 and 14 after nerve injury. [(11)C]PK11195 enhanced images were restricted to the L3-L6 area of the spinal cord. The standardized uptake value (SUV) of [(11)C]PK11195 was significantly increased in the lumbar spinal cord compared to that of the thoracic region. Increased specific binding of [(11)C]PK11195 to TSPO in the spinal cord of PSL rats was confirmed by competition studies using unlabeled (R, S)-PK11195. Increased [(3)H]PK11195 binding was also observed in the ipsilateral dorsal horn of the L3-L6 spinal cord on days 7 and 14 after nerve injury. CD11b mRNA and Iba1 immunoreactive cells increased significantly on days 7 and 14 after nerve injury by PSL. However, changes in GFAP mRNA and immunoreactivity were slight in the ipsilateral side of PSL rats. In the present study, we showed that glial activation could be quantitatively imaged in the spinal cord of neuropathic pain rats using [(11)C]PK11195 PET, suggesting that high resolution PET using TSPO-specific radioligands might be useful for imaging to assess the role of glial activation, including neuroinflammatory processes, in neuropathic pain patients.

Imamoto N; Momosaki S; Fujita M; Omachi S; Yamato H; Kimura M; Kanegawa N; Shinohara S; Abe K

2013-10-01

51

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

UK PubMed Central (United Kingdom)

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.Mucosal Immunology advance online publication 24 July 2013; doi:10.1038/mi.2013.52.

Ji H; Rabbi MF; Labis B; Pavlov VA; Tracey KJ; Ghia JE

2013-07-01

52

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

53

Intrinsic Cardiac Nerve Activity and Paroxysmal Atrial Tachyarrhythmia in Ambulatory Dogs  

Science.gov (United States)

Background Little is known about the relationship between intrinsic cardiac nerve activity (ICNA) and spontaneous arrhythmias in ambulatory animals. Methods and Results We implanted radiotransmitters to record extrinsic cardiac nerve activity (ECNA, including stellate ganglion nerve activity, SGNA; vagal nerve activity, VNA) and ICNA (including superior left ganglionated plexi nerve activity, SLGPNA; ligament of Marshall nerve activity, LOMNA) in 6 ambulatory dogs. Intermittent rapid left atrial pacing was performed to induce paroxysmal atrial fibrillation (PAF) or atrial tachycardia (PAT). The vast majority (94%) of LOMNA were preceded or co-activated with ECNA (SGNA or VNA), whereas 6% of episodes were activated alone without concomitant SGNA or VNA. PAF and PAT were invariably (100%) preceded (CFAE-like activity.

Choi, Eue-Keun; Shen, Mark J.; Han, Seongwook; Kim, Daehyeok; Hwang, Samuel; Sayfo, Sameh; Piccirillo, Gianfranco; Frick, Kyle; Fishbein, Michael C; Hwang, Chun; Lin, Shien-Fong; Chen, Peng-Sheng

2010-01-01

54

Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury.  

UK PubMed Central (United Kingdom)

Nestin-positive, keratin 15 (K15)-negative multipotent hair follicle stem cells are located above the hair follicle bulge. We have termed this location the hair follicle pluripotent stem cell area. We have previously shown that transplantation of nestin-expressing hair follicle stem cells can regenerate peripheral nerve and spinal cord injuries. In the present study, we regenerated the impinged sciatic nerve by transplanting hair follicle pluripotent stem cells. Human hair follicle stem cells were transplanted around the impinged sciatic nerve of ICR nude (nu/nu) mice. The hair follicle stem cells were transplanted between impinged sciatic nerve fragments of the mouse where they differentiated into glial fibrillary acidic protein-positive Schwann cells and promoted the recovery of pre-existing axons. The regenerated sciatic nerve functionally recovered. These multipotent hair follicle stem cells thereby provide a potential accessible, autologous source of stem cells for regeneration therapy of nerves degenerated by compression between bony or other hard surfaces.

Amoh Y; Aki R; Hamada Y; Niiyama S; Eshima K; Kawahara K; Sato Y; Tani Y; Hoffman RM; Katsuoka K

2012-01-01

55

Methods of assessing vagus nerve activity and reflexes.  

UK PubMed Central (United Kingdom)

The methods used to assess cardiac parasympathetic (cardiovagal) activity and its effects on the heart in both humans and animal models are reviewed. Heart rate (HR)-based methods include measurements of the HR response to blockade of muscarinic cholinergic receptors (parasympathetic tone), beat-to-beat HR variability (HRV) (parasympathetic modulation), rate of post-exercise HR recovery (parasympathetic reactivation), and reflex-mediated changes in HR evoked by activation or inhibition of sensory (afferent) nerves. Sources of excitatory afferent input that increase cardiovagal activity and decrease HR include baroreceptors, chemoreceptors, trigeminal receptors, and subsets of cardiopulmonary receptors with vagal afferents. Sources of inhibitory afferent input include pulmonary stretch receptors with vagal afferents and subsets of visceral and somatic receptors with spinal afferents. The different methods used to assess cardiovagal control of the heart engage different mechanisms, and therefore provide unique and complementary insights into underlying physiology and pathophysiology. In addition, techniques for direct recording of cardiovagal nerve activity in animals; the use of decerebrate and in vitro preparations that avoid confounding effects of anesthesia; cardiovagal control of cardiac conduction, contractility, and refractoriness; and noncholinergic mechanisms are described. Advantages and limitations of the various methods are addressed, and future directions are proposed.

Chapleau MW; Sabharwal R

2011-03-01

56

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

UK PubMed Central (United Kingdom)

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

Pereira Lopes FR; Frattini F; Marques SA; Almeida FM; de Moura Campos LC; Langone F; Lora S; Borojevic R; Martinez AM

2010-10-01

57

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

UK PubMed Central (United Kingdom)

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

Yoo PB; Lubock NB; Hincapie JG; Ruble SB; Hamann JJ; Grill WM

2013-04-01

58

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

Science.gov (United States)

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

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

2013-04-01

59

Neuregulin-1 type I: a hidden power within Schwann cells for triggering peripheral nerve remyelination.  

Science.gov (United States)

Physiological interactions and reciprocal signaling between axons and Schwann cells play critical roles in nerve development and survival. Axonally derived neuregulin-1 (NRG-1) type III is an essential modulator of Schwann cells during development, nerve repair, and remyelination. A recent report demonstrates an unexpected regulatory role for Schwann cell-derived NRG-1 type I in Schwann cell plasticity and remyelination after peripheral nerve injury. Specifically expressed in Schwann cells at critical time points after nerve injury, this isoform of NRG-1 emerges as a driving force for regeneration and remyelination programs. PMID:23572145

Krishnan, Anand

2013-04-09

60

Neuregulin-1 type I: a hidden power within Schwann cells for triggering peripheral nerve remyelination.  

UK PubMed Central (United Kingdom)

Physiological interactions and reciprocal signaling between axons and Schwann cells play critical roles in nerve development and survival. Axonally derived neuregulin-1 (NRG-1) type III is an essential modulator of Schwann cells during development, nerve repair, and remyelination. A recent report demonstrates an unexpected regulatory role for Schwann cell-derived NRG-1 type I in Schwann cell plasticity and remyelination after peripheral nerve injury. Specifically expressed in Schwann cells at critical time points after nerve injury, this isoform of NRG-1 emerges as a driving force for regeneration and remyelination programs.

Krishnan A

2013-04-01

 
 
 
 
61

Brimonidine protects against loss of Thy-1 promoter activation following optic nerve crush.  

UK PubMed Central (United Kingdom)

BACKGROUND: The loss of RGCs expressing Thy-1 after optic nerve injury has an initial phase of rapid decline followed by a longer phase with slower reduction rate. This study used longitudinal retinal imaging of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) to determine how the ?2-adrenergic agonist brimonidine influences loss of Thy1 promoter activation. METHODS: Baseline images of the fluorescent retinal neurons in 30 Thy1-CFP mice were obtained using a modified confocal scanning laser ophthalmoscope. Next, brimonidine (100 ug/kg, IP) was administered either one time immediately after optic nerve crush, or immediately after optic nerve crush and then every 2 days for four weeks. A control group received a single saline injection immediately after optic nerve crush. All animals were imaged weekly for four weeks after optic nerve crush. Loss of fluorescent retinal neurons within specific retinal areas was determined by counting. RESULTS: At one week after optic nerve crush, the proportion of fluorescent retinal neurons retaining fluorescence was 44±7% of baseline in control mice, 51±6% after one brimonidine treatment, and 55±6% after brimonidine treatment every other day (P<0.05 for both brimonidine treatment groups compared to the control group). Subsequently, the number of fluorescent retinal neurons in the group that received one treatment differed insignificantly from the control group. In contrast, the number of fluorescent retinal neurons in the group that received repeated brimonidine treatments was greater than the control group by 28% at two weeks after crush and by 32% at three weeks after crush (P<0.05 at both time points). Rate analysis showed that brimonidine slowed the initial rate of fluorescent cell decline in the animals that received multiple treatments (P<0.05). Differences in the rate of loss among the treatment groups were insignificant after the second week. CONCLUSION: Repeated brimonidine treatments protect against loss of fluorescence within fluorescent retinal neurons of Thy1-CFP mice after optic nerve crush. As most of fluorescent retinal neurons in this system are RGCs, these findings indicate that repeated brimonidine treatments may protect RGC health following optic nerve crush.

Dai Y; Lindsey JD; Duong-Polk KX; Chindasub P; Leung CK; Weinreb RN

2013-01-01

62

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; Tassoni Alessia; Bull Natalie D; Moschos Marilita M; Martin Keith R

2012-01-01

63

Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system.  

Science.gov (United States)

Various modifications including addition of Schwann cells or incorporation of growth factors with bioabsorbable nerve conduits have been explored as options for peripheral nerve repair. However, no reports of nerve conduits containing both supportive cells and growth factors have been published as a regenerative therapy for peripheral nerves. In the present study, sciatic nerve gaps in mice were reconstructed in the following groups: nerve conduit alone (control group), nerve conduit coated with induced pluripotent stem cell (iPSc)-derived neurospheres (iPSc group), nerve conduit coated with iPSc-derived neurospheres and basic fibroblast growth factor (bFGF)-incorporated gelatin microspheres (iPSc + bFGF group), and autograft. The fastest functional recovery and the greatest axon regeneration occurred in the autograft group, followed in order by the iPSc + bFGF group, iPSc group, and control group until 12 weeks after reconstruction. Thus, peripheral nerve regeneration using nerve conduits and functional recovery in mice was accelerated by a combination of iPSc-derived neurospheres and a bFGF drug delivery system. The combination of all three fundamental methodologies, iPSc technology for supportive cells, bioabsorbable nerve conduits for scaffolds, and a bFGF drug delivery system for growth factors, was essential for peripheral nerve regenerative therapy. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. PMID:23733515

Ikeda, Mikinori; Uemura, Takuya; Takamatsu, Kiyohito; Okada, Mitsuhiro; Kazuki, Kenichi; Tabata, Yasuhiko; Ikada, Yoshito; Nakamura, Hiroaki

2013-06-01

64

Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system.  

UK PubMed Central (United Kingdom)

Various modifications including addition of Schwann cells or incorporation of growth factors with bioabsorbable nerve conduits have been explored as options for peripheral nerve repair. However, no reports of nerve conduits containing both supportive cells and growth factors have been published as a regenerative therapy for peripheral nerves. In the present study, sciatic nerve gaps in mice were reconstructed in the following groups: nerve conduit alone (control group), nerve conduit coated with induced pluripotent stem cell (iPSc)-derived neurospheres (iPSc group), nerve conduit coated with iPSc-derived neurospheres and basic fibroblast growth factor (bFGF)-incorporated gelatin microspheres (iPSc+bFGF group), and autograft. The fastest functional recovery and the greatest axon regeneration occurred in the autograft group, followed in order by the iPSc+bFGF group, iPSc group, and control group until 12 weeks after reconstruction. Thus, peripheral nerve regeneration using nerve conduits and functional recovery in mice was accelerated by a combination of iPSc-derived neurospheres and a bFGF drug delivery system. The combination of all three fundamental methodologies, iPSc technology for supportive cells, bioabsorbable nerve conduits for scaffolds, and a bFGF drug delivery system for growth factors, was essential for peripheral nerve regenerative therapy.

Ikeda M; Uemura T; Takamatsu K; Okada M; Kazuki K; Tabata Y; Ikada Y; Nakamura H

2013-06-01

65

Adipose-Derived Stem Cells Stimulate Regeneration of Peripheral Nerves: BDNF Secreted by These Cells Promotes Nerve Healing and Axon Growth De Novo  

Science.gov (United States)

Transplantation of adipose-derived mesenchymal stem cells (ASCs) induces tissue regeneration by accelerating the growth of blood vessels and nerve. However, mechanisms by which they accelerate the growth of nerve fibers are only partially understood. We used transplantation of ASCs with subcutaneous matrigel implants (well-known in vivo model of angiogenesis) and model of mice limb reinnervation to check the influence of ASC on nerve growth. Here we show that ASCs stimulate the regeneration of nerves in innervated mice's limbs and induce axon growth in subcutaneous matrigel implants. To investigate the mechanism of this action we analyzed different properties of these cells and showed that they express numerous genes of neurotrophins and extracellular matrix proteins required for the nerve growth and myelination. Induction of neural differentiation of ASCs enhances production of brain-derived neurotrophic factor (BDNF) as well as ability of these cells to induce nerve fiber growth. BDNF neutralizing antibodies abrogated the stimulatory effects of ASCs on the growth of nerve sprouts. These data suggest that ASCs induce nerve repair and growth via BDNF production. This stimulatory effect can be further enhanced by culturing the cells in neural differentiation medium prior to transplantation.

Lopatina, Tatiana; Kalinina, Natalia; Karagyaur, Maxim; Stambolsky, Dmitry; Rubina, Kseniya; Revischin, Alexander; Pavlova, Galina; Parfyonova, Yelena; Tkachuk, Vsevolod

2011-01-01

66

Polymer hollow fiber-encapsulated peripheral nerve extracts change their activity towards injured hippocampal neurites in rats.  

UK PubMed Central (United Kingdom)

The regeneration of the adult mammalian central nervous system (CNS) requires changes of the nonpromising environment. Applying peripheral nerve grafts and their extracts are both the useful method to induce regeneration of injured CNS neurites. Our previous reports showed that degeneration of peripheral nerves enhanced their neurotrophic activity in a time-dependent manner. Electrophoretical analysis of proteins obtained from degenerating sciatic nerves revealed significant changes in fractions of low molecular mass. The aim of the present work was to examine the influence of fractionated extracts from 7-day-predegenerated and non-predegenerated peripheral nerves upon injured hippocampal neurites in adult rats. The extracts were closed in fibrin-filled connective tissue chambers (CTC) or within CTC-wrapped polymer hollow fibers (PHF) of 30 kDa cut-off. The cell bodies of regrowing fibers were labeled with FITC-HRP. The CTCs appeared to be useful tool for implantation of artificial grafts into mammalian CNS. Full-spectrum nerve extracts induced strong regeneration of injured hippocampal neurites. The number of labeled cells within hippocampus was significantly lower in PHF groups than in CTC ones, indicating that low-mass proteins present in peripheral nerve extracts are not sufficient to induce successful regeneration.

Larysz-Brysz M; Kotulska K; Górkal D; Golka B; Marcol W; Lewin-Kowalik J

2007-09-01

67

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

UK PubMed Central (United Kingdom)

Spinal afferent neurons play a major role in detecting noxious and innocuous stimuli from visceral organs, such as the gastrointestinal tract. However, all our understanding about spinal afferents has been obtained from recordings of spinal afferent axons, or cell bodies that lie outside the gut wall, or peripheral organ they innervate. No recordings have been made directly from spinal afferent nerve endings, which is where sensory transduction occurs. We developed a preparation whereby recordings could be made from rectal afferent nerve endings in the colon, to characterize mechanisms underlying sensory transduction. Dorsal root ganglia (L6-S2) were removed from mice, whilst retaining neural continuity with the colon. Fluo-4-AM was used to record from rectal afferent nerve endings in myenteric ganglia and circular muscle at 36°C. In slack (unstretched) preparations of colon, no calcium transients were recorded from spinal afferent endings. However, in response to a maintained increase in circumferential diameter, a maintained discharge of calcium transients occurred simultaneously in multiple discrete varicosities along single axons of rectal afferents in myenteric ganglia and circular muscle. Stretch-activated calcium transients were resistant to hexamethonium and nifedipine, but were abolished by tetrodotoxin, CPA, BAPTA-AM, cobalt, gadolinium, or replacement of extracellular Na(+) with NMDG. In summary, we present a novel preparation in which stretch-activated firing of spinal afferent nerve endings can be recorded, using calcium imaging. We show that circumferential stretch of the colon activates a maintained discharge of calcium transients simultaneously in varicosities along single rectal afferent endings in myenteric ganglia and circular muscle. Non-selective cation channels, TTX-sensitive Na(+) channels and both extracellular calcium influx and intracellular Ca(2+) stores are required for stretch-activated calcium transients in rectal afferent endings.

Travis L; Spencer NJ

2013-01-01

68

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

Science.gov (United States)

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

Travis, Lee; Spencer, Nick J.

2013-01-01

69

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

Science.gov (United States)

Spinal afferent neurons play a major role in detecting noxious and innocuous stimuli from visceral organs, such as the gastrointestinal tract. However, all our understanding about spinal afferents has been obtained from recordings of spinal afferent axons, or cell bodies that lie outside the gut wall, or peripheral organ they innervate. No recordings have been made directly from spinal afferent nerve endings, which is where sensory transduction occurs. We developed a preparation whereby recordings could be made from rectal afferent nerve endings in the colon, to characterize mechanisms underlying sensory transduction. Dorsal root ganglia (L6-S2) were removed from mice, whilst retaining neural continuity with the colon. Fluo-4-AM was used to record from rectal afferent nerve endings in myenteric ganglia and circular muscle at 36°C. In slack (unstretched) preparations of colon, no calcium transients were recorded from spinal afferent endings. However, in response to a maintained increase in circumferential diameter, a maintained discharge of calcium transients occurred simultaneously in multiple discrete varicosities along single axons of rectal afferents in myenteric ganglia and circular muscle. Stretch-activated calcium transients were resistant to hexamethonium and nifedipine, but were abolished by tetrodotoxin, CPA, BAPTA-AM, cobalt, gadolinium, or replacement of extracellular Na(+) with NMDG. In summary, we present a novel preparation in which stretch-activated firing of spinal afferent nerve endings can be recorded, using calcium imaging. We show that circumferential stretch of the colon activates a maintained discharge of calcium transients simultaneously in varicosities along single rectal afferent endings in myenteric ganglia and circular muscle. Non-selective cation channels, TTX-sensitive Na(+) channels and both extracellular calcium influx and intracellular Ca(2+) stores are required for stretch-activated calcium transients in rectal afferent endings. PMID:24109427

Travis, Lee; Spencer, Nick J

2013-10-07

70

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.)

1981-06-09

71

HIF-1 expression in retinal ganglion cells and optic nerve axons in glaucoma HIF-1 expression in retinal ganglion cells and optic nerve axons in glaucoma  

Directory of Open Access Journals (Sweden)

Full Text Available Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells andoptic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinalganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% ofcases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the stainingwas evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression inhypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerveaxons, and might be a successful target for the implementation of neuroprotective drugs.Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells andoptic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinalganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% ofcases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the stainingwas evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression inhypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerveaxons, and might be a successful target for the implementation of neuroprotective drugs.

Joanna Resze?; Renata Zalewska; Piotr Bernaczyk; Lech Chyczewski

2012-01-01

72

Instability of spatial encoding by CA1 hippocampal place cells after peripheral nerve injury.  

UK PubMed Central (United Kingdom)

Several authors have shown that the hippocampus responds to painful stimulation and suggested that prolonged painful conditions could lead to abnormal hippocampal functioning. The aim of the present study was to evaluate whether the induction of persistent peripheral neuropathic pain would affect basic hippocampal processing such as the spatial encoding performed by CA1 place cells. These place cells fire preferentially in a certain spatial position in the environment, and this spatial mapping remains stable across multiple experimental sessions even when the animal is removed from the testing environment. To address the effect of prolonged pain on the stability of place cell encoding, we chronically implanted arrays of electrodes in the CA1 hippocampal region of adult rats and recorded the multichannel neuronal activity during a simple food-reinforced alternation task in a U-shaped runway. The activity of place cells was followed over a 3-week period before and after the establishment of an animal model of neuropathy, spared nerve injury. Our results show that the nerve injury increased the number of place fields encoded per cell and the mapping size of the place fields. In addition, there was an increase in in-field coherence while the amount of spatial information content that a single spike conveyed about the animal location decreased over time. Other measures of spatial tuning (in-field firing rate, firing peak and number of spikes) were unchanged between the experimental groups. These results demonstrate that the functioning of spatial place cells is altered during neuropathic pain conditions.

Cardoso-Cruz H; Lima D; Galhardo V

2011-06-01

73

Co-expression of activin receptor-interacting protein 1 and 2 in mouse nerve cells.  

UK PubMed Central (United Kingdom)

Activin is a neurotrophic and neuroprotective factor in the central nervous system. Activin receptor-interacting protein 1 and 2 (ARIP1 and ARIP2) are identified as activin signal proteins in mouse brain. However, whether ARIP1 and ARIP2 are co-expressed in nerve cells and the differences of their biological activities are not well characterized. In the present study, we found that ARIP1 and ARIP2 mRNA expressions were detectable in mouse brain and their proteins were co-localized at the hypothalamus of cerebrum and granular layers in cerebellum, especially in Purkinje cells. Furthermore, ARIP1 and ARIP2 were co-expressed in mouse Neuro-2a cells, which is similar to the co-localization of ARIP1 and ARIP2 in hypothalamus neurons and Purkinje cells. Overexpression of ARIP1 in Neuro-2a cells inhibited activin signal transduction induced by activin A and Smad3, and activin A-induced voltage-gated Na(+) current (INa), while ARIP2 was only a negative regulator of signal transduction induced by activin A and did not alter activin A-induced INa. Taken together, these data demonstrate that ARIP1 and ARIP2 are co-expressed in some nerve cells and their biological activities are distinct.

Qi Y; Ge JY; Wang YN; Liu HY; Li YM; Liu ZH; Cui XL

2013-05-01

74

Peripheral nerve regeneration using autologous porcine skin-derived mesenchymal stem cells.  

UK PubMed Central (United Kingdom)

Porcine skin-derived mesenchymal stem cells (pSMSCs) were evaluated on their biological MSC characterizations and differentiation into mesenchymal lineages, along with in vitro and in vivo neural inductions. Isolated pSMSCs showed plate-adherent growth, expression of various MSC-marker proteins and transcriptional factors, and differentiation potential into mesenchymal lineages. Neuron-like cell morphology and various neural markers were highly detected at 6 h and 24 h after in vitro neural induction of pSMSCs, but their neuron-like characteristics disappeared as induction time extended to 48 and 72 h. To evaluate the in vivo peripheral nerve regeneration potential of pSMSCs, a total of 5 × 10(6) autologous pSMSCs labelled with tracking dye, supplemented with fibrin glue scaffold and collagen tubulization, were transplanted into the peripheral nerve defected miniature pigs. At 2 and 4 weeks after cell transplantation, well-preserved transplanted cells and remarkable in vivo nerve regeneration, including histologically complete nerve bundles, were observed in the regenerated nerve tissues. Moreover, S-100 protein and p75 nerve growth factor receptor were more highly detected in regenerated nerve fibres compared to non-cell grafted control fibres. These results suggest that autologous pSMSCs transplanted with fibrin glue scaffold can induce prominent nerve regeneration in porcine peripheral nerve defect sites.

Park BW; Kang DH; Kang EJ; Byun JH; Lee JS; Maeng GH; Rho GJ

2012-02-01

75

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

UK PubMed Central (United Kingdom)

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

Reid AJ; Sun M; Wiberg M; Downes S; Terenghi G; Kingham PJ

2011-12-01

76

Identification of a Peripheral Nerve Neurite Growth-Promoting Activity by Development and Use of an in vitro Bioassay  

Science.gov (United States)

The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay.

Sandrock, Alfred W.; Matthew, William D.

1987-10-01

77

Peripheral electrical nerve stimulation and rest-activity rhythm in Alzheimer's disease.  

Science.gov (United States)

Rest-activity rhythm disruption is a prominent clinical feature of Alzheimer's disease (AD). The origin of the altered rest-activity rhythm is believed to be degeneration of the suprachiasmatic nucleus (SCN). In accordance with the 'use it or lose it' hypothesis of Swaab [Neurobiol Aging 1991, 12: 317-324] stimulation of the SCN may prevent age-related loss of neurons and might reactivate nerve cells that are inactive but not lost. Previous studies with relatively small sample sizes have demonstrated positive effects of peripheral electrical nerve stimulation on the rest-activity rhythm in AD patients. The present randomized, placebo-controlled, parallel-group study was meant to replicate prior findings of electrical stimulation in AD in a substantially larger group of AD patients. The experimental group (n = 31) received peripheral electrical nerve stimulation and the placebo group (n = 31) received sham stimulation. Effects of the intervention on the rest-activity rhythm were assessed by using wrist-worn actigraphs. Near-significant findings on the rest-activity rhythm partially support the hypothesis that neuronal stimulation enhances the rest-activity rhythm in AD patients. Interestingly, post-hoc analyses revealed significant treatment effects in a group of patients who were not using acetylcholinesterase inhibitors concomitantly. We conclude that more research is needed before firm general conclusions about the effectiveness of electrical stimulation as a symptomatic treatment in AD can be drawn. In addition, the present post-hoc findings indicate that future studies on non-pharmacological interventions should take medication use into account. PMID:17118098

Van Dijk, Koene R A; Luijpen, Marijn W; Van Someren, Eus J W; Sergeant, Joseph A; Scheltens, Philip; Scherder, Erik J A

2006-12-01

78

Adipose-Derived Stem Cells and Nerve Regeneration: Promises and Pitfalls.  

UK PubMed Central (United Kingdom)

In order to improve the outcome of nerve regeneration following peripheral trauma injuries, the development of bioengineered nerve grafts has attracted great attention in the field of tissue engineering. Adult stem cells constitute the ideal alternative to Schwann cells (SCs) as transplantable cells in bioartificial nerve grafts. Among the various sources of stem cells with potential applications for regenerative medicine, the adipose tissue has been proven to be one of the most promising. Adipose-derived stem cells (ASCs) are easily obtained, rapidly expanded, show low immunogenicity, and can be differentiated into SCs in vitro. This chapter will focus on recent advances in the use of differentiated and undifferentiated ASCs for peripheral nerve regeneration, with a critical attention for the clinical exploitability of ASC in nerve repair strategies.

Faroni A; Terenghi G; Reid AJ

2013-01-01

79

Laser-activated adhesive films for sutureless median nerve anastomosis.  

UK PubMed Central (United Kingdom)

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. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

Barton M; Morley JW; Stoodley MA; Ng KS; Piller SC; Duong H; Mawad D; Mahns DA; Lauto A

2013-05-01

80

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. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). 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

2013-05-28

 
 
 
 
81

Toxicity induced by cumene hydroperoxide in leech Retzius nerve cells: the protective role of glutathione.  

Science.gov (United States)

In the present study, we studied the ability of glutathione (GSH) to detoxify exogenously applied cumene hydroperoxide (CHP). Exposure of leech Retzius nerve cells to CHP (1.5 mM) induced a marked prolongation of the spontaneous spike potential of these cells. Early after depolarization, and a cardiac-like action potential with a rapid depolarization followed by a sustained depolarization or plateau, which is terminated by a rapid repolarization were recorded. GSH (0.2 mM) significantly inhibited the effects of CHP on the duration of the action potential and suppressed CHP-induced spontaneous repetitive activity. Voltage-clamp recordings showed that CHP (1.5 mM) caused significant changes in the outward potassium currents. The fast and slow steady part of the potassium outward current was reduced by 46% and 39%, respectively. GSH applied in a concentration of 0.2 mM partially blocked the effect of CHP on the calcium-activated potassium currents. The fast and slow calcium-activated potassium currents were suppressed by about 20% and 15%, respectively. These results suggest that the neurotoxic effect of CHP on spontaneous spike electrogenesis and calcium-activated potassium currents of leech Retzius nerve cells was reduced in the presence of GSH. PMID:23767299

Jovanovic, Zorica; Jovanovic, Svetlana

2013-01-01

82

Toxicity induced by cumene hydroperoxide in leech Retzius nerve cells: the protective role of glutathione.  

UK PubMed Central (United Kingdom)

In the present study, we studied the ability of glutathione (GSH) to detoxify exogenously applied cumene hydroperoxide (CHP). Exposure of leech Retzius nerve cells to CHP (1.5 mM) induced a marked prolongation of the spontaneous spike potential of these cells. Early after depolarization, and a cardiac-like action potential with a rapid depolarization followed by a sustained depolarization or plateau, which is terminated by a rapid repolarization were recorded. GSH (0.2 mM) significantly inhibited the effects of CHP on the duration of the action potential and suppressed CHP-induced spontaneous repetitive activity. Voltage-clamp recordings showed that CHP (1.5 mM) caused significant changes in the outward potassium currents. The fast and slow steady part of the potassium outward current was reduced by 46% and 39%, respectively. GSH applied in a concentration of 0.2 mM partially blocked the effect of CHP on the calcium-activated potassium currents. The fast and slow calcium-activated potassium currents were suppressed by about 20% and 15%, respectively. These results suggest that the neurotoxic effect of CHP on spontaneous spike electrogenesis and calcium-activated potassium currents of leech Retzius nerve cells was reduced in the presence of GSH.

Jovanovic Z; Jovanovic S

2013-01-01

83

The effect of Staphylococcus aureus enterotoxin A on proliferation of lymphoid and nerve cells.  

UK PubMed Central (United Kingdom)

The effects of Staphylococcus aureus enterotoxin A (SEA) on proliferative activities of human peripheral blood lymphocytes, B-lymphoma cells of the Namalva line, and nerve cells of the PC12 line have been studied. It has been shown that SEA affects these cells in identical ways, producing either a mitogenic or an antiproliferative effect. Studies on the dynamics of cellular responses to the action of SEA have demonstrated that the effects of the toxin are mediated by its interaction with different binding sites on the membranes of target cells. It has been established also that the antiproliferative effect of SEA is not associated with changes in 2',5'-oligo(A)-synthetase activity or in the level of interferon secretion.

Alakhov VYu; Moskaleva EYu; Kravtzova TN; Smirnov VV; Duvakin IA; Loginov BV; Severin ES

1988-12-01

84

The effect of Staphylococcus aureus enterotoxin A on proliferation of lymphoid and nerve cells.  

Science.gov (United States)

The effects of Staphylococcus aureus enterotoxin A (SEA) on proliferative activities of human peripheral blood lymphocytes, B-lymphoma cells of the Namalva line, and nerve cells of the PC12 line have been studied. It has been shown that SEA affects these cells in identical ways, producing either a mitogenic or an antiproliferative effect. Studies on the dynamics of cellular responses to the action of SEA have demonstrated that the effects of the toxin are mediated by its interaction with different binding sites on the membranes of target cells. It has been established also that the antiproliferative effect of SEA is not associated with changes in 2',5'-oligo(A)-synthetase activity or in the level of interferon secretion. PMID:3233148

Alakhov VYu; Moskaleva EYu; Kravtzova, T N; Smirnov, V V; Duvakin, I A; Loginov, B V; Severin, E S

1988-12-01

85

Ozone activates airway nerves via the selective stimulation of TRPA1 ion channels.  

UK PubMed Central (United Kingdom)

Inhalation of ozone is a major health risk in industrialized nations. Ozone can impair lung function and induce respiratory symptoms through sensory neural-mediated pathways, yet the specific interaction of ozone with airway sensory nerves has yet to be elucidated. Here we demonstrate, using a vagally innervated ex vivo tracheal-lung mouse preparation, that ozone selectively and directly evokes action potential discharge in a subset of nociceptive bronchopulmonary nerves, namely slow conducting C-fibres. Sensitivity to ozone correlated with the transient receptor potential (TRP) A1 agonist, cinnamaldehyde, with ozone having no effect on cinnamaldehyde-insensitive fibres. C-fibre responses to ozone were abolished by ruthenium red (TRP inhibitor). Ozone also stimulated a subset of nociceptive sensory neurones isolated from vagal ganglia of wild-type mice, but failed to activate neurones isolated from transient receptor potential ankyrin 1 (TRPA1) knockout mice. Ozone activated HEK293 cells transfected with TRPA1, but failed to activate non-transfected HEK293 or HEK293 transfected with the capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1) channel. Thus, ozone is not an indiscriminate neuronal activator, but rather it potently and selectively activates a subset of airway C-fibres by directly stimulating TRPA1.

Taylor-Clark TE; Undem BJ

2010-02-01

86

3D reconstitution of nerve-blood vessel networks using skeletal muscle-derived multipotent stem cell sheet pellets.  

UK PubMed Central (United Kingdom)

AIM: To cover the large tissue deficits associated with significant loss of function following surgery, a 3D gel-patch-like nerve-vascular reconstitution system was developed using the skeletal muscle-derived multipotent stem cell (Sk-MSC) sheet pellet. MATERIALS & METHODS: The Sk-MSC sheet pellet was prepared from GFP transgenic mice by the collagenase extraction and 7 days expansion cell culture, and transplanted into a severe muscle damage model with large disruptions to muscle fibers, blood vessels and peripheral nerves. RESULTS: At 4 weeks after transplantation, engrafted cells contributed to nerve-vascular regeneration associated with cellular differentiation into Schwann cells, perineurial/endoneurial cells, vascular endothelial cells and pericytes. However, skeletal myogenic differentiation was scarcely observed. Paracrine effects regarding donor cells/tissues could also be expected, because of the active expression of neurogenic and vasculogenic factor mRNAs in the sheet pellet. CONCLUSION: These results indicate that the vigorous skeletal myogenic potential of Sk-MSCs was clearly reduced in the sheet pellet preparation and this method may be a useful adjuvant for nerve-vascular regeneration in various tissue engineering applications.

Tamaki T; Soeda S; Hashimoto H; Saito K; Sakai A; Nakajima N; Masuda M; Fukunishi N; Uchiyama Y; Terachi T; Mochida J

2013-07-01

87

Generation of Schwann cell-derived multipotent neurospheres isolated from intact sciatic nerve.  

Science.gov (United States)

Schwann cells (SCs) are the supporting cells of the peripheral nervous system and originate from the neural crest. They play a unique role in the regeneration of injured peripheral nerves and have themselves a highly unstable phenotype as demonstrated by their unexpectedly broad differentiation potential. Thus, SCs can be considered as dormant, multipotent neural crest-derived progenitors or stem cells. Upon injury they de-differentiate via cellular reprogramming, re-enter the cell cycle and participate in the regeneration of the nerve. Here we describe a protocol for efficient generation of neurospheres from intact adult rat and murine sciatic nerve without the need of experimental in vivo pre-degeneration of the nerve prior to Schwann cell isolation. After isolation and removal of the connective tissue, the nerves are initially plated on poly-D-lysine coated cell culture plates followed by migration of the cells up to 80% confluence and a subsequent switch to serum-free medium leading to formation of multipotent neurospheres. In this context, migration of SCs from the isolated nerve, followed by serum-free cultivation of isolated SCs as neurospheres mimics the injury and reprograms fully differentiated SCs into a multipotent, neural crest-derived stem cell phenotype. This protocol allows reproducible generation of multipotent Schwann cell-derived neurospheres from sciatic nerve through cellular reprogramming by culture, potentially marking a starting point for future detailed investigations of the de-differentiation process. PMID:22664741

Martin, Ina; Nguyen, The Duy; Krell, Vivien; Greiner, Johannes F W; Müller, Janine; Hauser, Stefan; Heimann, Peter; Widera, Darius

2012-12-01

88

Redox regulation of nerve growth factor-induced neuronal differentiation of PC12 cells through modulation of the nerve growth factor receptor, TrkA.  

UK PubMed Central (United Kingdom)

We investigated the effects of the cellular redox state on nerve growth factor (NGF)-induced neuronal differentiation and its signaling pathways. Treatment of PC12 cells with buthionine sulfoximine (BSO) reduced the levels of GSH, a major cellular reductant, and enhanced NGF-induced neuronal differentiation, activation of AP-1 and the NGF receptor tyrosine kinase, TrkA. Conversely, incubation of the cells with a reductant, N-acetyl-L-cysteine (NAC), inhibited NGF-induced neuronal differentiation and AP-1 activation. Consistent with the suppression, NAC inhibited NGF-induced activation of TrkA, formation of receptor complexes comprising TrkA, Shc, Grb2, and Sos, and activation of phospholipase Cgamma and phosphatidylinositol 3-kinase. Biochemical analysis suggested that the cellular redox state regulates TrkA activity through modulation of protein tyrosine phosphatases (PTPs). Thus, cellular redox state regulates signaling pathway of NGF through PTPs, and then modulates neuronal differentiation.

Kamata H; Oka S; Shibukawa Y; Kakuta J; Hirata H

2005-02-01

89

Peripheral nerve repair with cultured schwann cells: getting closer to the clinics.  

UK PubMed Central (United Kingdom)

Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiated in vitro into Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated bone marrow mesenchymal cells can be associated with nerve conduits and afterward transplanted. Experimental studies provide evidence of functional, histological, and electromyographical improvement following transplantation of bone-marrow-derived cells in animal models of peripheral nerve injury. This paper focuses on this new therapeutic approach highlighting its direct translational and clinical utility in promoting regeneration of not only acute but perhaps also chronic cases of peripheral nerve damage.

Rodrigues MC; Rodrigues AA Jr; Glover LE; Voltarelli J; Borlongan CV

2012-01-01

90

Lentiviral Vector-Mediated Gradients of GDNF in the Injured Peripheral Nerve: Effects on Nerve Coil Formation, Schwann Cell Maturation and Myelination  

Science.gov (United States)

Although the peripheral nerve is capable of regeneration, only a small minority of patients regain normal function after surgical reconstruction of a major peripheral nerve lesion, resulting in a severe and lasting negative impact on the quality of life. Glial cell-line derived neurotrophic factor (GDNF) has potent survival- and outgrowth-promoting effects on motoneurons, but locally elevated levels of GDNF cause trapping of regenerating axons and the formation of nerve coils. This phenomenon has been called the “candy store” effect. In this study we created gradients of GDNF in the sciatic nerve after a ventral root avulsion. This approach also allowed us to study the effect of increasing concentrations of GDNF on Schwann cell proliferation and morphology in the injured peripheral nerve. We demonstrate that lentiviral vectors can be used to create a 4 cm long GDNF gradient in the intact and lesioned rat sciatic nerve. Nerve coils were formed throughout the gradient and the number and size of the nerve coils increased with increasing GDNF levels in the nerve. In the nerve coils, Schwann cell density is increased, their morphology is disrupted and myelination of axons is severely impaired. The total number of regenerated and surviving motoneurons is not enhanced after the distal application of a GDNF gradient, but increased sprouting does result in higher number of motor axon in the distal segment of the sciatic nerve. These results show that lentiviral vector mediated overexpression of GDNF exerts multiple effects on both Schwann cells and axons and that nerve coil formation already occurs at relatively low concentrations of exogenous GDNF. Controlled expression of GDNF, by using a viral vector with regulatable GDNF expression, may be required to avoid motor axon trapping and to prevent the effects on Schwann cell proliferation and myelination.

Eggers, Ruben; de Winter, Fred; Hoyng, Stefan A.; Roet, Kasper C. D.; Ehlert, Erich M.; Malessy, Martijn J. A.; Verhaagen, Joost; Tannemaat, Martijn R.

2013-01-01

91

Lentiviral Vector-Mediated Gradients of GDNF in the Injured Peripheral Nerve: Effects on Nerve Coil Formation, Schwann Cell Maturation and Myelination.  

UK PubMed Central (United Kingdom)

Although the peripheral nerve is capable of regeneration, only a small minority of patients regain normal function after surgical reconstruction of a major peripheral nerve lesion, resulting in a severe and lasting negative impact on the quality of life. Glial cell-line derived neurotrophic factor (GDNF) has potent survival- and outgrowth-promoting effects on motoneurons, but locally elevated levels of GDNF cause trapping of regenerating axons and the formation of nerve coils. This phenomenon has been called the "candy store" effect. In this study we created gradients of GDNF in the sciatic nerve after a ventral root avulsion. This approach also allowed us to study the effect of increasing concentrations of GDNF on Schwann cell proliferation and morphology in the injured peripheral nerve. We demonstrate that lentiviral vectors can be used to create a 4 cm long GDNF gradient in the intact and lesioned rat sciatic nerve. Nerve coils were formed throughout the gradient and the number and size of the nerve coils increased with increasing GDNF levels in the nerve. In the nerve coils, Schwann cell density is increased, their morphology is disrupted and myelination of axons is severely impaired. The total number of regenerated and surviving motoneurons is not enhanced after the distal application of a GDNF gradient, but increased sprouting does result in higher number of motor axon in the distal segment of the sciatic nerve. These results show that lentiviral vector mediated overexpression of GDNF exerts multiple effects on both Schwann cells and axons and that nerve coil formation already occurs at relatively low concentrations of exogenous GDNF. Controlled expression of GDNF, by using a viral vector with regulatable GDNF expression, may be required to avoid motor axon trapping and to prevent the effects on Schwann cell proliferation and myelination.

Eggers R; de Winter F; Hoyng SA; Roet KC; Ehlert EM; Malessy MJ; Verhaagen J; Tannemaat MR

2013-01-01

92

[Peripheral nerve myelin antigen-specific T cells in human  

UK PubMed Central (United Kingdom)

In recent years, anti-myelin glycolipid antibodies have been reported to be specific for acute inflammatory demyelinating polyneuritis (AIDP) so the involvement of autoimmune mechanism by such autoantibodies was strongly suggested as a cause of AIDP. However, the cellular immunity of AIDP has been seldom reported yet. To examine the T cell response to peripheral nerve antigens in human, we tried to establish T cell lines reactive to peripheral myelin antigens. P0 56-71, P0 180-199 and P2 59-78 peptides from human peripheral blood of controls and patients with inflammatory demyelinating polyneuritis. Frequencies of T cells reactive with P0 56-71, P0 180-199 and P2 59-78 peptides in five controls were (0.59 +/- 0.81) x 10(-7), (1.53 +/- 0.53) x 10(-7) and (0.11 +/- 0.24) x 10(-7), respectively. Frequency of P0 180-199-reactive T cells in one AIDP patient of acute stage was 3.5 x 10(-7) and approximately 2 times high value of controls. There is no significant association between their frequency and specific MHC class II genotypes in subjects until now. Thus, peripheral myelin antigen-specific T cell lines in particular recognizing P0 180-199 were established from the majority of controls and polyneuritis patients. These results suggest that the residues of P0 180-199 might be one of T cell epitopes also in human subjects.

Ota K; Shimizu Y; Ueda M; Akiyama N; Iwata M

1996-07-01

93

Modulation of renal sympathetic nerve activity during pneumoperitoneum in rats.  

Science.gov (United States)

To examine neural control of renal function during pneumoperitoneum, renal sympathetic nerve activity (RSNA) was measured in pentobarbital-anesthetized rats that had their entire nervous system intact or that had undergone lower thoracic dorsal rhizotomy or abdominal vagotomy. During pneumoperitoneum with intraabdominal pressure (IAP) of 10 mmHg, the mean arterial pressure did not change, but central venous pressure increased by 10 mmHg in all groups. In intact rats, the RSNA increased to 285 +/- 22% during pneumoperitoneum and gradually recovered after release of the insufflation. The RSNA responses decreased during pneumoperitoneum in rats with dorsal rhizotomy or vagotomy compared to responses in intact rats. In intact rats the urine volume and Na+ excretion decreased during pneumoperitoneum and increased just after insufflation release. Dorsal rhizotomy, vagotomy, or renal denervation did not alter the antidiuretic and antinatriuretic responses during pneumoperitoneum; however, diuretic and natriuretic responses were completely abolished by either of these denervations following insufflation release. These results suggest that oliguria during pneumoperitoneum was not due to neural control of renal function but probably to a mechanical influence induced by the elevated IAP. On the other hand, diuretic and natriuretic responses after insufflation release were thought to be a neurally mediated response. PMID:12297938

Tanaka, Kunihiko; Tsuchiya, Yo; Ree, Ken; Morita, Hironobu

2002-09-26

94

Binding and internalization of nerve growth factor by PC12 cells  

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

Kasaian, M.T.

1987-01-01

95

Magnetite nanoparticles doped photoresist derived carbon as a suitable substratum for nerve cell culture.  

UK PubMed Central (United Kingdom)

A method which alters the substrate's physical and electrochemical properties by doping photoresist derived carbon with magnetite nanoparticles has been developed to enhance the existing substrate's ability to foster cell growth. Cyclic voltammetry, scanning electron microscopy and atomic force microscopy are used to evaluate the characters of the prepared film. And then, the magnetite nanoparticles doped carbon film is used as substrate for the growth of nerve cell. Here, rat pheochromocytoma cells are used for culture to test substrate-cell interactions. The results showed an increase in cell concentration and average neurite length with the increase of nanoparticle concentration on the surface. Importantly, the nerve cells can be grown on the magnetite nanoparticles doped carbon even in the absence of nerve growth factor. This finding will potentially provide a new material for nerve regeneration.

Zhu Z; Rezhdo O; Perrone M; Bao Z; Munir A; Wang J; Zhou HS; Shao J

2013-02-01

96

Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Functional muscle recovery after peripheral nerve injury is far from optimal, partly due to atrophy of the muscle arising from prolonged denervation. We hypothesized that injecting regenerative cells into denervated muscle would reduce this atrophy. METHODS: A rat sciatic nerve lesion was performed, and Schwann cells or adipose-derived stem cells, untreated or induced to a "Schwann-cell-like" phenotype (dASC), were injected into the gastrocnemius muscle. Nerves were either repaired immediately or capped to prevent muscle reinnervation. One month later, functionality was measured using a walking track test, and muscle atrophy was assessed by examining muscle weight and histology. RESULTS: Schwann cells and dASC groups showed significantly better scores on functional tests when compared with injections of growth medium alone. Muscle weight and histology were also significantly improved in these groups. CONCLUSION: Cell injections may reduce muscle atrophy and could benefit nerve injury patients.

Schaakxs D; Kalbermatten DF; Raffoul W; Wiberg M; Kingham PJ

2013-05-01

97

Perineural Invasion of Cutaneous Squamous Cell Carcinoma Along the Zygomaticotemporal Nerve.  

UK PubMed Central (United Kingdom)

The vast majority of periocular squamous cell carcinoma spreads intraorbitally along the supraorbital and infraorbital nerves into the cavernous sinus. A patient presented with a history of resected squamous cell carcinoma and pain in the zygomatic distribution. She was found to have temporalis involvement of the malignancy and invasion of the zygomaticotemporal nerve by histopathology. She underwent aggressive resection and adjuvant treatment with no evidence of recurrence at 8-month follow up. This case illustrates an uncommon route of squamous cell carcinoma spread through the zygomaticotemporal sensory nerve distribution.

Notz G; Cognetti D; Murchison AP; Bilyk JR

2013-08-01

98

Synergistic effects of low-level laser and mesenchymal stem cells on functional recovery in rats with crushed sciatic nerves.  

UK PubMed Central (United Kingdom)

Transplantation of mesenchymal stem cells (MSCs) has been proposed to exert beneficial effects on peripheral nerve regeneration after a peripheral nerve injury, but the functional recovery in the denervated limb is still limited. In this study, we used low-level laser therapy (LLLT) as an adjunct therapy for MSC transplantation on the functional recovery of crushed sciatic nerve in rats. Peripheral nerve injury was induced in 48 Sprague-Dawley rats by crushing the unilateral sciatic nerve, using a vessel clamp. The animals with crushed injury were randomly divided into four groups: control group, with no treatment; MSC group, treated with MSC alone; LLLT group, treated with LLLT alone; and MSCLLLT group, treated with a combination of MSC and LLLT. The sciatic function index (SFI), vertical activity of locomotion (VA) and ankle angle (AA) of rats were examined for functional assessments after treatment. Electrophysiological, morphological and S100 immunohistochemical studies were also conducted. The MSCLLLT group showed a greater recovery in SFI, VA and AA, with significant difference from MSC, LLLT and control groups (p?cells and less vacuole formation were also demonstrated after nerve crush injury in the MSCLLLT group when compared with the groups receiving a single treatment (p?nerve crush injury. Copyright © 2013 John Wiley & Sons, Ltd.

Yang CC; Wang J; Chen SC; Hsieh YL

2013-03-01

99

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.

Toda Shigeru; Sakai Atsushi; Ikeda Yumiko; Sakamoto Atsuhiro; Suzuki Hidenori

2011-01-01

100

Pax2 regulates neuronal-glial cell fate choice in the embryonic optic nerve.  

Science.gov (United States)

During development, neural cell fate in the vertebrate optic nerve is restricted to the astroglial lineage. However, when isolated from the embryo and explanted in vitro, optic nerve progenitors generate neurons instead of astrocytes, suggesting that neuronal potentialities exist and are repressed in progenitors in vivo. Here we have investigated the mechanisms controlling cell fate in the optic nerve. The optic nerve is characterized by expression of the homeodomain transcription factor Pax2 which is maintained in differentiated astrocytes. We have observed that Pax2 is rapidly down-regulated in explanted optic nerves that generate neurons, and that its overexpression by electroporation in the optic nerve, or ectopically in the neural tube, is sufficient to block neuronal differentiation and allow glial development, showing that Pax2 plays a major role in controlling cell fate in the optic nerve. In vitro and ex vivo experiments further show that a signaling cascade that involves successively Sonic hedgehog and FGF is required to maintain Pax2 expression in optic nerve precursors whereby inhibiting the neuronal fate and promoting astroglial differentiation. PMID:17173889

Soukkarieh, Chadi; Agius, Eric; Soula, Cathy; Cochard, Philippe

2006-11-11

 
 
 
 
101

Elimination of microwave effects on the vitality of nerves after blockage of active transport  

Energy Technology Data Exchange (ETDEWEB)

We have previously reported that exposure to microwave fields (a specific absorption rate of 10 W/kg at 2.45-GHz continuous wave) would consistently lower the survival time of isolated frog sciatic nerves stimulated at high repetition rates (50 pulse pairs per second, ppps). The time course of the loss of excitability of the exposed nerve (as compared to its unexposed contralateral mate) is reminiscent of that seen when the active transport of sodium (Na) and potassium (K) is blocked by certain agents--such as the cardiac glycoside ouabain. To assess the role that these microwaves may have in interfering with or counteracting active transport, we performed a series of experiments in which the active Na-K pump was substantially blocked by ouabain prior to microwave exposure. The paired nerves were soaked for 5 min in a high concentration (10(-3) g/liter) of ouabain to achieve the fastest and most complete blockage of the Na-K pump prior to stimulation at 50 ppps. The ''rundown time course'' was, as expected, accelerated in all ouabain-treated nerves, but the microwave-exposed nerves showed no additional shortening of survival time. The experiments were repeated at a slower stimulation rate (5 ppps) so that the survival time of the nerves more closely approximated that of nerves not treated with ouabain (1 to 2 h versus 30 min or less for ouabain-treated nerves stimulated at 50 ppps). Results of these lower stimulation rates also showed that there was no significant difference in the survival time of ouabain-treated exposed and control nerves. These results lend support to the view that the relative loss of excitability in microwave-exposed nerves is related to an interference with or counteraction of the Na-K pump.

McRee, D.I.; Wachtel, H.

1986-12-01

102

Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury.  

Science.gov (United States)

Nestin-positive, keratin 15 (K15)-negative multipotent hair follicle stem cells are located above the hair follicle bulge. We have termed this location the hair follicle pluripotent stem cell area. We have previously shown that transplantation of nestin-expressing hair follicle stem cells can regenerate peripheral nerve and spinal cord injuries. In the present study, we regenerated the impinged sciatic nerve by transplanting hair follicle pluripotent stem cells. Human hair follicle stem cells were transplanted around the impinged sciatic nerve of ICR nude (nu/nu) mice. The hair follicle stem cells were transplanted between impinged sciatic nerve fragments of the mouse where they differentiated into glial fibrillary acidic protein-positive Schwann cells and promoted the recovery of pre-existing axons. The regenerated sciatic nerve functionally recovered. These multipotent hair follicle stem cells thereby provide a potential accessible, autologous source of stem cells for regeneration therapy of nerves degenerated by compression between bony or other hard surfaces. PMID:22098554

Amoh, Yasuyuki; Aki, Ryoichi; Hamada, Yuko; Niiyama, Shiro; Eshima, Koji; Kawahara, Katsumasa; Sato, Yuichi; Tani, Yoichi; Hoffman, Robert M; Katsuoka, Kensei

2011-11-21

103

Mast cells can contribute to axon-glial dissociation and fibrosis in peripheral nerve.  

UK PubMed Central (United Kingdom)

Expression of the human epidermal growth factor receptor (EGFR) in murine Schwann cells results in loss of axon-Schwann cell interactions and collagen deposition, modeling peripheral nerve response to injury and tumorigenesis. Mast cells infiltrate nerves in all three situations. We show that mast cells are present in normal mouse peripheral nerve beginning at 4 weeks of age, and that the number of mast-cells in EGFR(+) nerves increases abruptly at 5-6 weeks of age as axons and Schwann cells dissociate. The increase in mast cell number is preceded and accompanied by elevated levels of mRNAs encoding the mast-cell chemoattractants Rantes, SCF and VEGF. Genetic ablation of mast cells and bone marrow reconstitution in W(41) x EGFR(+) mice indicate a role for mast cells in loss of axon-Schwann cell interactions and collagen deposition. Pharmacological stabilization of mast cells by disodium cromoglycate administration to EGFR(+) mice also diminished loss of axon-Schwann cell interaction. Together these three lines of evidence support the hypothesis that mast cells can contribute to alterations in peripheral nerves.

Monk KR; Wu J; Williams JP; Finney BA; Fitzgerald ME; Filippi MD; Ratner N

2007-08-01

104

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

UK PubMed Central (United Kingdom)

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

May F; Buchner A; Schlenker B; Gratzke C; Arndt C; Stief C; Weidner N; Matiasek K

2013-03-01

105

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 regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab.

1994-01-01

106

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

Energy Technology Data Exchange (ETDEWEB)

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 [times] three fractions/48 h or 5 Gy/fractions [times] 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 regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab.

Iwai, Hiroyuki; Matsuno, Etsuko (Daikin Industries, Ltd., Settsu (Japan)); Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta (Kyoto Univ. (Japan))

1994-06-15

107

Protection by an Oral Disubstituted Hydroxylamine Derivative against Loss of Retinal Ganglion Cell Differentiation following Optic Nerve Crush.  

UK PubMed Central (United Kingdom)

Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs). Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440) protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO). These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury.

Lindsey JD; Duong-Polk KX; Dai Y; Nguyen DH; Leung CK; Weinreb RN

2013-01-01

108

Protection by an Oral Disubstituted Hydroxylamine Derivative against Loss of Retinal Ganglion Cell Differentiation following Optic Nerve Crush.  

Science.gov (United States)

Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs). Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440) protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO). These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury. PMID:23940507

Lindsey, James D; Duong-Polk, Karen X; Dai, Yi; Nguyen, Duy H; Leung, Christopher K; Weinreb, Robert N

2013-08-05

109

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

110

Effects of Cardiac Resynchronization Therapy on Muscle Sympathetic Nerve Activity.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Muscle sympathetic nerve activity (MSNA) is an independent prognostic marker in patients with heart failure (HF). Therefore, its relevance to the treatment of HF patients is unquestionable. OBJECTIVES: In this study, we investigated the effects of cardiac resynchronization therapy (CRT) on MSNA response at rest and during exercise in patients with advanced HF. METHODS: We assessed 11 HF patients (51 ± 3.4 years; New York Heart Association class III-IV; left ventricular ejection fraction 27.8 ± 2.2%; optimal medical therapy) submitted to CRT. Evaluations were made prior to and 3 months after CRT. MSNA was performed at rest and during moderate static exercise (handgrip). Peak oxygen consumption (VO2 ) was evaluated by means of cardiopulmonary exercise test. HF patients with advanced NYHA class without CRT and healthy individuals were also studied. RESULTS: CRT reduced MSNA at rest (48.9 ± 11.1 bursts/min vs 33.7 ± 15.3 bursts/min, P < 0.05) and during handgrip exercise (MSNA 62.3 ± 13.1 bursts/min vs 46.9 ± 14.3 bursts/min, P < 0.05). Among HF patients submitted to CRT, the peak VO2 increased (12.9 ± 2.8 mL/kg/min vs 16.5 ± 3.9 mL/kg/min, P < 0.05) and an inverse correlation between peak VO2 and resting MSNA (r = -0.74, P = 0.01) was observed. CONCLUSIONS: In patients with advanced HF and severe systolic dysfunction: (1) a significant reduction of MSNA (at rest and during handgrip) occurred after CRT, and this behavior was significantly superior to HF patients receiving only medical therapy; (2) MSNA reduction after CRT had an inverse correlation with O2 consumption outcomes.

Kuniyoshi RR; Martinelli M; Negrão CE; Siqueira SF; Rondon MU; Trombetta IC; Kuniyoshi FH; Laterza MC; Nishioka SA; Costa R; Tamaki WT; Crevelari ES; Peixoto GD; Ramires JA; Kalil R

2013-08-01

111

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.

2009-02-20

112

Subclinical doses of the nerve gas sarin impair T cell responses through the autonomic nervous system.  

UK PubMed Central (United Kingdom)

The nerve gas sarin is a potent cholinergic agent, and exposure to high doses may cause neurotoxicity and death. Subclinical exposures to sarin have been postulated to contribute to the Gulf War syndrome; however, the biological effects of subclinical exposure are largely unknown. In this communication, evidence shows that subclinical doses (0.2 and 0.4 mg/m(3)) of sarin administered by inhalation to F344 rats for 1 h/day for 5 or 10 days inhibited the anti-sheep red blood cell antibody-forming cell response of spleen cells without affecting the distribution of lymphocyte subpopulations in the spleen. Moreover, sarin suppressed T cell responses, including the concanavalin A (Con A) and the anti-alphabeta-T cell receptor (TCR) antibody-induced T cell proliferation and the rise in the intracellular calcium following TCR ligation. These concentrations of sarin altered regional but not total brain acetylcholinesterase activity. Interestingly, serum corticosterone levels of the sarin-treated animals were dramatically lower than the control animals, indicating that sarin-induced immunosuppression did not result from the activation of the hypothalamus-pituitary-adrenal (HPA) axis. Pretreatment of animals with the ganglionic blocker chlorisondamine abrogated the inhibitory effects of sarin on spleen cell proliferation in response to Con A and anti-TCR antibodies. These results suggest that the effects of sarin on T cell responsiveness are mediated via the autonomic nervous system and are independent of the HPA axis.

Kalra R; Singh SP; Razani-Boroujerdi S; Langley RJ; Blackwell WB; Henderson RF; Sopori ML

2002-10-01

113

[Bone marrow derived cells promoting pre-degeneration of sciatic nerve in vitro].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To explore a new method for the pre-degeneration of peripheral nerve in vitro for obtaining many effective Schwann cells so as to provide a large number of seed cells for the research and application of tissue engineered nerves. METHODS: The bone marrow derived cells (BMDCs) from transgenic green fluorescent protein C57BL/6 mouse and the sciatic nerve segments from the C57BL/6 mouse were co-cultured to prepare the pre-degeneration of sciatic nerve in vitro (experimental group, group A), and only sciatic nerve was cultured (control group, group B). At 7 days after culture, whether BMDCs can permeate into the sciatic nerve in vitro for pre-degeneration was observed by gross and immunohistofluorescence staining. And then Schwann cells were obtained from the sciatic nerves by enzymic digestion and cultured. The cell number was counted, and then the purity of primary Schwann cells was determined using immunohistofluorescence staining and flow cytometer analysis. RESULTS: At 7 days after pre-degeneration, gross observation showed that enlargement was observed at nerve stumps, and neuroma-like structure formed; the group A was more obvious than group B. Immunohistofluorescence staining showed many BMDCs permeated into the nerve segments, with positive F4/80 staining in group A. After culture, the yield of Schwann cells was (5.59 +/- 0.19) x 10(4) /mg in group A and (3.20 +/-0.21) x 10(4)/mg in group B, showing significant difference (t=2.14, P=0.03). At 48 hours after inoculation, the cells had blue bipolar or tripolar cell nuclei with small size and red soma by immunohistofluorescence staining; fibroblasts were flat polygonal with clear nucleus and nucleolus, showing negative p75NTR staining; and there were few of fibroblasts in group A. The purity of Schwann cells was 88.4% +/- 5.8% in group A and 76.1% +/-3.7% in group B, showing significant difference (t=2.38, P=0.04). And the flow cytometer analysis showed that the purity was 89.6% in group A and 74.9% in group B. CONCLUSION: BMDCs can promote the pre-degeneration of peripheral nerve in vitro, and it is a new method to effectively obtain Schwann cells for tissue engineered nerve.

Wu M; Wang X; Xiao Y; Zhou J

2013-05-01

114

Intrathecal lamotrigine attenuates mechanical allodynia and suppresses microglial and astrocytic activation in a rat model of spinal nerve ligation.  

UK PubMed Central (United Kingdom)

PURPOSE: Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats. MATERIALS AND METHODS: Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 ?g/day) or saline continuously for 7 days. Mechanical allodynia of the left hind paw to von Frey filament stimuli was determined before surgery (baseline) and once daily for 7 days postoperatively. On day 7, spinal activation of microglia and astrocytes was evaluated immunohistochemically, using antibodies to the microglial marker OX-42 and the astrocyte marker glial fibrillary acidic protein (GFAP). RESULTS: Spinal-nerve ligation induced mechanical allodynia in saline-treated rats, with OX-42 and GFAP immunoreactivity being significantly increased on the ipsilateral side of the spinal cord. Continuously administered intrathecal lamotrigine (240 ?g/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 ?g/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 ?g/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP. CONCLUSION: Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.

Choi YS; Jun IG; Kim SH; Park JY

2013-03-01

115

Electrophysiological characterization of voltage-gated K(+) currents in cerebellar basket and purkinje cells: Kv1 and Kv3 channel subfamilies are present in basket cell nerve terminals.  

UK PubMed Central (United Kingdom)

To understand the processes underlying fast synaptic transmission in the mammalian CNS, we must have detailed knowledge of the identity, location, and physiology of the ion channels in the neuronal membrane. From labeling studies we can get clues regarding the distribution of ion channels, but electrophysiological methods are required to determine the importance of each ion channel in CNS transmission. Dendrotoxin-sensitive potassium channel subunits are highly concentrated in cerebellar basket cell nerve terminals, and we have previously shown that they are responsible for a significant fraction of the voltage-gated potassium current in this region. Here, we further investigate the characteristics and pharmacology of the voltage-dependent potassium currents in these inhibitory nerve terminals and compare these observations with those obtained from somatic recordings in basket and Purkinje cell soma regions. We find that alpha-DTX blocks basket cell nerve terminal currents and not somatic currents, and the IC(50) for alpha-DTX in basket cell terminals is 3.2 nM. There are at least two distinct types of potassium currents in the nerve terminal, a DTX-sensitive low-threshold component, and a second component that activates at much more positive voltages. Pharmacological experiments also reveal that nerve terminal potassium currents are also markedly reduced by 4-AP and TEA, with both high-sensitivity (micromolar) and low-sensitivity (millimolar) components present. We suggest that basket cell nerve terminals have potassium channels from both the Kv1 and Kv3 subfamilies, whereas somatic currents in basket cell and Purkinje cell bodies are more homogeneous.

Southan AP; Robertson B

2000-01-01

116

GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA.  

Science.gov (United States)

The monosialoganglioside GM1 has been shown to possess neurotrophic activity in vitro and in vivo and is now used as an experimental treatment for a variety of neurological disorders and trauma. Little is known about the mechanism of action used by GM1. Because GM1 appears to enhance nerve growth factor (NGF) activity, we have used C6trk+ cells, a derivative of C6-2B glioma cells that express the high-affinity receptor for NGF trkA, to determine whether the neurotrophic effects of GM1 occurs through induction of trkA activity. Exposure of C6trk+ cells to NGF (10-50 ng/ml) resulted in a five- to 10-fold increase in trkA tyrosine phosphorylation within 5 min. Incubation of cells with GM1 resulted in a threefold increase in trkA phosphorylation beginning within 1 h and peaking between 3 and 6 h. Optimal responses to GM1 were obtained using 80-100 microM concentrations. Moreover, tyrosine phosphorylation of known trkA target proteins, such as extracellular signal-regulated kinases, and suc-associated neurotrophic factor-induced tyrosine-phosphorylated target, were activated upon stimulation of C6trk+ cells with GM1. In addition, GM1 potentiated the NGF-mediated activation of tyrosine phosphorylation of trkA. GM1 failed to induce phosphorylation of trkA and target proteins in mock transfected cells. Thus, our data demonstrate that GM1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM1 may be attributed to its activation of trkA signal transduction. PMID:7790879

Rabin, S J; Mocchetti, I

1995-07-01

117

GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA.  

UK PubMed Central (United Kingdom)

The monosialoganglioside GM1 has been shown to possess neurotrophic activity in vitro and in vivo and is now used as an experimental treatment for a variety of neurological disorders and trauma. Little is known about the mechanism of action used by GM1. Because GM1 appears to enhance nerve growth factor (NGF) activity, we have used C6trk+ cells, a derivative of C6-2B glioma cells that express the high-affinity receptor for NGF trkA, to determine whether the neurotrophic effects of GM1 occurs through induction of trkA activity. Exposure of C6trk+ cells to NGF (10-50 ng/ml) resulted in a five- to 10-fold increase in trkA tyrosine phosphorylation within 5 min. Incubation of cells with GM1 resulted in a threefold increase in trkA phosphorylation beginning within 1 h and peaking between 3 and 6 h. Optimal responses to GM1 were obtained using 80-100 microM concentrations. Moreover, tyrosine phosphorylation of known trkA target proteins, such as extracellular signal-regulated kinases, and suc-associated neurotrophic factor-induced tyrosine-phosphorylated target, were activated upon stimulation of C6trk+ cells with GM1. In addition, GM1 potentiated the NGF-mediated activation of tyrosine phosphorylation of trkA. GM1 failed to induce phosphorylation of trkA and target proteins in mock transfected cells. Thus, our data demonstrate that GM1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM1 may be attributed to its activation of trkA signal transduction.

Rabin SJ; Mocchetti I

1995-07-01

118

Effects of undifferentiated cultured omental adipose-derived stem cells on peripheral nerve regeneration.  

UK PubMed Central (United Kingdom)

BACKGROUND/AIMS: Employment of regenerative properties of stem cells at the service of nerve repair has been initiated during recent decades. Effects of transplantation of undifferentiated cultured omental adipose-derived stem cells (uADSCs) on peripheral nerve regeneration were studied using a rat sciatic nerve transection model. METHODS: A 10-mm sciatic nerve defect was bridged using a silicone rubber chamber filled with uADSCs. In control group, the silicone conduit was filled with phosphate-buffered saline alone. The regenerated nerve fibers were studied 4, 8, and 12wk after surgery. In sham-operated group, the sciatic nerve was only exposed and manipulated. RESULTS: Functional study confirmed faster recovery of regenerated axons in uADSC-transplanted animals than in control group (P<0.05). Gastrocnemius muscle mass in uADSC-transplanted animals is found to be significantly more than that in control group. Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in uADSC-transplanted animals than in control group. In immunohistochemistry, location of reactions to S-100 in uADSC-transplanted animals was clearly more positive than that in control group. CONCLUSION: uADSC transplantation could be considered as a readily accessible source of stromal cells that improve functional recovery of sciatic nerve.

Mohammadi R; Azizi S; Amini K

2013-04-01

119

Bone marrow stromal cells and resorbable collagen guidance tubes enhance sciatic nerve regeneration in mice.  

UK PubMed Central (United Kingdom)

We evaluated peripheral nerve regeneration using a tubular nerve guide of resorbable collagen filled with either bone marrow-derived cells (BMDCs) in Dulbecco's cell culture medium (DMEM) or with DMEM alone (control). The control group received just the culture medium (vehicle). The left sciatic nerves of ten isogenic mice were transected and the tubular nerve guides were sutured to the end of the proximal and distal nerve stumps. Motor function was tested at 2, 4 and 6 weeks after surgery using the walking track test. The pawprints were analyzed and the print lengths (PL) were measured to evaluate functional recovery. After 6 weeks, mice were anesthetized, perfused transcardially with fixative containing aldehydes, and the sciatic nerves and tubes were dissected and processed for scanning and transmission electron microscopy. Scanning electron microscopy of the collagen tube revealed that the tube wall became progressively thinner after surgery, proving that the tube can be resorbed in vivo. Quantitative analysis of the regenerating nerves showed that the number of myelinated fibers and the myelin area were significantly increased in the experimental group. Also, motor function recovery was faster in animals that received the cell grafts. These results indicate that the collagen tube filled with BMDCs provided an adequate and favorable environment for the growth and myelination of regenerating axons compared to the collagen tube alone.

Pereira Lopes FR; Camargo de Moura Campos L; Dias Corrêa J Jr; Balduino A; Lora S; Langone F; Borojevic R; Blanco Martinez AM

2006-04-01

120

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

UK PubMed Central (United Kingdom)

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.

Kuca K; Musilek K; Jun D; Karasova J; Soukup O; Pejchal J; Hrabinova M

2013-08-01

 
 
 
 
121

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

122

Signals regulating myelination in peripheral nerves and the Schwann cell response to injury.  

UK PubMed Central (United Kingdom)

In peripheral nerves, Schwann cells form myelin, which facilitates the rapid conduction of action potentials along axons in the vertebrate nervous system. Myelinating Schwann cells are derived from neural crest progenitors in a step-wise process that is regulated by extracellular signals and transcription factors. In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves. In response to injury, myelinating Schwann cells dedifferentiate into repair cells that are essential for axonal regeneration, and then redifferentiate into myelinating Schwann cells to restore nerve function. Although this remarkable plasticity has long been recognized, many questions remain unanswered regarding the signaling pathways regulating both myelination and the Schwann cell response to injury.

Glenn TD; Talbot WS

2013-07-01

123

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

DEFF Research Database (Denmark)

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

Moldovan, Mihai; Krarup, Christian

2006-01-01

124

Nerve supply to the inner sensory cells in a human cochlea.  

Science.gov (United States)

A choclear apical turn taken from a 66-year-old woman showed an area with marked decrease in number of the inner sensory cells. After observation by scanning electron microscope, the same specimen was thin-sectioned tangentially to the osseous spiral lamina. Numbers of myelinated nerve fibers were counted and the thickness of the fiber was measured by computed measuring equipment. Compared to the area with inner sensory cells intact, the area without inner sensory cells showed a 70% decrease in number of myelinated fibers. These degenerated fibers might have had intimate relationship with the inner sensory cells, probably being the afferent nerve supply to the inner sensory cells. PMID:475658

Hoshino, T; Kodama, A

1979-01-01

125

Nerve supply to the inner sensory cells in a human cochlea.  

UK PubMed Central (United Kingdom)

A choclear apical turn taken from a 66-year-old woman showed an area with marked decrease in number of the inner sensory cells. After observation by scanning electron microscope, the same specimen was thin-sectioned tangentially to the osseous spiral lamina. Numbers of myelinated nerve fibers were counted and the thickness of the fiber was measured by computed measuring equipment. Compared to the area with inner sensory cells intact, the area without inner sensory cells showed a 70% decrease in number of myelinated fibers. These degenerated fibers might have had intimate relationship with the inner sensory cells, probably being the afferent nerve supply to the inner sensory cells.

Hoshino T; Kodama A

1979-01-01

126

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

International Nuclear Information System (INIS)

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

2013-01-01

127

[Adaptation of motor nerve fibers to physical activity  

UK PubMed Central (United Kingdom)

The effects induced by training on the H-reflex of soleus and lateral gastrocnemius muscles have been studied on 19 adult male volunteers; out of these, 10 were non-trained subjects and the remaining 9 were top level athletes engaged in sports requiring very rapid and intense contractions (sprinters and volley-ball players). It has been observed that the latency of the M response is significantly higher in the athletes than in the non-trained subjects. Instead, no significant differences were observed between these two groups, concerning the latency of H response. The increase of M response latency is likely due to a decrease of nerve conduction velocity in the terminal part of motor fibers. The possibility that this conduction speed decrease could be dependent on sprouting and/or terminal branching growth of the motor nerve ending is discussed.

Perciavalle V; Casabona A; Polizzi MC

1990-11-01

128

A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration.  

Science.gov (United States)

While an important role for the POU domain transcription factor Oct-6 in the developing peripheral nerve has been well established, studies into its exact role in nerve development and regeneration have been hampered by the high mortality rate of newborn Oct-6 mutant animals. In this study we have generated a Schwann cell-specific Oct-6 allele through deletion of the Schwann cell-specific enhancer element (SCE) in the Oct-6 locus. Analysis of mice homozygous for this allele (deltaSCE allele) reveals that rate-limiting levels of Oct-6 in Schwann cells are dependent on the SCE and that this element does not contribute to Oct-6 regulation in other cell types. We demonstrate a Schwann cell autonomous function for Oct-6 during nerve development as well as in regenerating nerve. Additionally, we show that Krox-20, an important regulatory target of Oct-6 in Schwann cells, is activated, with delayed kinetics, through an Oct-6-independent mechanism in these mice. PMID:12198163

Ghazvini, Merhnaz; Mandemakers, Wim; Jaegle, Martine; Piirsoo, Marko; Driegen, Siska; Koutsourakis, Manousos; Smit, Xsander; Grosveld, Frank; Meijer, Dies

2002-09-01

129

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

2007-01-01

130

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

2007-11-15

131

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.

Romon Rodrigue; Adriaenssens Eric; Lagadec Chann; Germain Emmanuelle; Hondermarck Hubert; Le Bourhis Xuefen

2010-01-01

132

Synergistic lithium chloride and glial cell line-derived neurotrophic factor delivery for peripheral nerve repair in a rodent sciatic nerve injury model.  

UK PubMed Central (United Kingdom)

BACKGROUND: Restoring peripheral nerve function after long gap peripheral nerve damage is challenging. Lithium chloride has demonstrated neuroprotective qualities and therefore shows great potential therapeutic benefit for some neurodegenerative diseases. This study examined the synergistic combination of glial cell line-derived neurotrophic factor and lithium chloride and its effect on peripheral nerve regeneration in a rat sciatic nerve injury model. METHODS: Polycaprolactone conduits with glial cell line-derived neurotrophic factor-loaded double-walled microspheres and local injections of lithium chloride, 1.5 or 2.5 mEq/kg body weight, were examined in a 15-mm rat sciatic nerve defect model. Eighteen Lewis male rats were divided randomly into control, 1.5-, and 2.5-mEq/kg lithium chloride injection groups. As an indicator of recovery, nerve sections were stained with S100, protein gene product 9.5 antibody, and toluidine blue. RESULTS: Nerves stained with S100 and protein gene product 9.5 antibody demonstrated a significantly increased density of Schwann cells and axons in the 2.5-mEq/kg lithium chloride injection-treated groups compared with both the control and 1.5-mEq/kg lithium chloride injection-treated groups (p<0.05). At 6 weeks, histomorphometry revealed a significantly higher fiber density in the middle of the conduit for the 2.5-mEq/kg groups compared with the 1.5-mEq/kg group or the control group. CONCLUSION: Polycaprolactone nerve guides with glial cell line-derived neurotrophic factor-loaded double-walled microspheres and local injections of lithium chloride, 2.5-mEq/kg, represent a potentially viable guiding material for Schwann cell and axon migration and proliferation for the treatment of peripheral nerve regeneration.

Lin YC; Oh SJ; Marra KG

2013-08-01

133

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

Science.gov (United States)

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

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

2013-04-02

134

The neuroprotective effect of resveratrol on retinal ganglion cells after optic nerve transection.  

UK PubMed Central (United Kingdom)

PURPOSE: This study aimed to investigate the neuroprotective effect of resveratrol in an optic nerve transection (ONT) model and to identify the neuroprotective mechanism of resveratrol in retinal ganglion cells (RGCs). METHODS: ONT and retrograde labeling were performed in Sprague-Dawley rats. Various concentrations of resveratrol were injected intravitreally immediately after ONT. The number of labeled RGCs was determined at 1 and 2 weeks after ONT. The effect of resveratrol and sirtinol (a sirtuin 1 inhibitor) co-injection was investigated. RGC-5 cells were cultured and treated with staurosporine to induce differentiation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the effect of resveratrol on RGC-5 cell survival under serum-free conditions. RGC-5 cells were cultured with sirtinol to investigate the neuroprotective mechanism of resveratrol. RESULTS: A dose-response relationship was observed between resveratrol and RGC survival. A single intravitreal injection of resveratrol was neuroprotective in RGCs at 1 week after ONT (p<0.01). Repeated intravitreal injection of resveratrol showed a neuroprotective effect at 2 weeks after ONT (p<0.01). However, co-injection of resveratrol and sirtinol diminished the neuroprotective effect of resveratrol (p<0.05). The neuroprotective effect of resveratrol was observed in RGC-5 cells under serum-free conditions, and sirtinol diminished this neuroprotective effect. CONCLUSIONS: Resveratrol exerts its neuroprotective effect on RGCs via activation of the sirtuin 1 pathway in an ONT model. This finding demonstrates the therapeutic potential of resveratrol in treating optic nerve diseases.

Kim SH; Park JH; Kim YJ; Park KH

2013-01-01

135

Inhibition of EphA4 expression promotes Schwann cell migration and peripheral nerve regeneration.  

UK PubMed Central (United Kingdom)

Erythropoietin-producing hepatocellular carcinoma receptors (Ephs) and their ligands Ephrins can affect axon growth. To evaluate the efficacy of EphA4 knockdown on Schwann cell migration and peripheral nerve regeneration, we detected EphA4 levels in Schwann cells. To knock down the expression of EphA4 in Schwann cell, two independent small interfering RNAs (siRNAs) were designed, and Schwann cell migration was examined. Four days after surgery, sciatic nerve sections of wild-type (WT) and EphA4(-/-) rats were examined by immunofluorescence, and axonal outgrowth was analyzed. The EphA4 protein could be detected in Schwann cells from intact nerves. EphA4 mediates the inhibitory effect on Schwann cell migration, and EphA4 knock-down can strongly increase Schwann cell migration and peripheral nerve regeneration. Knocking-down the expression of EphA4 promotes peripheral axon growth in vivo. It may provide a potential strategy for the recovery of peripheral nerve injury.

Wang Y; Zheng Z; Hu D

2013-08-01

136

Inhibition of EphA4 expression promotes Schwann cell migration and peripheral nerve regeneration.  

Science.gov (United States)

Erythropoietin-producing hepatocellular carcinoma receptors (Ephs) and their ligands Ephrins can affect axon growth. To evaluate the efficacy of EphA4 knockdown on Schwann cell migration and peripheral nerve regeneration, we detected EphA4 levels in Schwann cells. To knock down the expression of EphA4 in Schwann cell, two independent small interfering RNAs (siRNAs) were designed, and Schwann cell migration was examined. Four days after surgery, sciatic nerve sections of wild-type (WT) and EphA4(-/-) rats were examined by immunofluorescence, and axonal outgrowth was analyzed. The EphA4 protein could be detected in Schwann cells from intact nerves. EphA4 mediates the inhibitory effect on Schwann cell migration, and EphA4 knock-down can strongly increase Schwann cell migration and peripheral nerve regeneration. Knocking-down the expression of EphA4 promotes peripheral axon growth in vivo. It may provide a potential strategy for the recovery of peripheral nerve injury. PMID:23689248

Wang, Yaojun; Zheng, Zhao; Hu, Dahai

2013-05-17

137

Magnetic resonance imaging monitoring dual-labeled stem cells for treatment of mouse nerve injury.  

UK PubMed Central (United Kingdom)

BACKGROUND AIMS: Adipose-derived stem cells (ADSCs) have shown great promise in the regenerative repair of injured peripheral nerves. Magnetic resonance imaging (MRI) has provided attractive advantages in tracking superparamagnetic iron oxide nanoparticle (SPION)-labeled cells and evaluating their fate after cell transplantation. This study investigated the feasibility of the use of MRI to noninvasively track ADSCs repair of peripheral nerve injury in vivo. METHODS: Green fluorescent protein (GFP)-expressing ADSCs were isolated, expanded, differentiated into an SC-like phenotype (GFP-dADSCs) at early passages and subsequently labeled with SPIONs. The morphological and functional properties of the GFP-dADSCs were assessed through the use of immunohistochemistry. The intracellular stability, proliferation and viability of the labeled cells were evaluated in vitro. Through the use of a microsurgical procedure, the labeled cells were then seeded into sciatic nerve conduits in C57/BL6 mice to repair a 1-cm sciatic nerve gap. A clinical 3-T MRI was performed to investigate the GFP-dADSCs in vitro and the transplanted GFP-dADSCs inside the sciatic nerve conduits in vivo. RESULTS: The GFP-dADSCs were efficiently labeled with SPIONs, without affecting their viability and proliferation. The labeled cells implanted into the mice sciatic nerve conduit exhibited a significant increase in axonal regeneration compared with the empty conduit and could be detected by MRI. Fluorescent microscopic examination, histological analysis and immunohistochemistry confirmed the axon regeneration and MRI results. CONCLUSIONS: These data will elucidate the neuroplasticity of ADSCs and provide a new protocol for in vivo tracking of stem cells that are seeded to repair injured peripheral nerves.

Li K; Qin J; Wang X; Xu Y; Shen Z; Lu X; Zhang G

2013-10-01

138

Galectin-3 is upregulated in microglial cells in response to ischemic brain lesions, but not to facial nerve axotomy.  

Science.gov (United States)

We have recently demonstrated that the beta-galactoside-specific lectin galectin-3 is expressed by microglial cells in vitro, but not by normal resting microglia in vivo. In the present study, we have analyzed the expression of galectin-3 by microglia under traumatic conditions in vivo using two experimental rat models which substantially differ in the severity of lesion related to a breakdown of the blood-brain barrier (BBB) and the occurrence of inflammatory processes. These two features are absent after peripheral nerve lesion and present after cerebral ischemia. Here we show that, following facial nerve axotomy under conditions allowing (nerve anastomosis) or not subsequent regeneration (nerve resection), galectin-3 is not expressed by microglia in the corresponding facial nucleus 1-112 days after lesion. Galectin-3 is also absent in microglia at sites of a defective BBB in the normal brain, such as the circumventricular organs. Following experimental ischemia (i.e., permanent occlusion of the middle cerebral artery), in contrast, galectin-3 becomes strongly expressed by activated microglia as early as 48 hours after trauma, as determined by immunohistochemistry and Western blot analysis. Our findings suggest that the expression of galectin-3 by microglia in vivo correlates with the state of microglial activation. PMID:10931529

Walther, M; Kuklinski, S; Pesheva, P; Guntinas-Lichius, O; Angelov, D N; Neiss, W F; Asou, H; Probstmeier, R

2000-08-15

139

A ganglion cell cluster along the glossopharyngeal nerve near the human palatine tonsil.  

UK PubMed Central (United Kingdom)

CONCLUSION: The lingual branches of the glossopharyngeal nerve were most likely to bring not only gustatory nerves to the postsulcal part of the tongue but also autonomic nerves to the small glands and vessels. Tonsillectomy may injure the ganglion or reduce its function due to scar formation after surgery. OBJECTIVES: To determine the topographical anatomy of a suggested ganglion cluster along the lingual branches of the glossopharyngeal nerve and to identify the incidence. METHODS: In the human pharynges of 12 donated cadavers, we studied the ganglia using routine procedures for paraffin-embedded histology and immunohistochemistry. RESULTS: Near the palatine tonsil, the lingual branches of the glossopharyngeal nerve often contained ganglion cells (in 9 of 12 specimens). The ganglion cells, 20-40 µ in diameter, were sparsely distributed along a 0.5-3.0 mm length of the nerve course attached to the posterolateral aspect of the superior pharyngeal constrictor. Most of these cells were positive for neuronal nitric oxide synthase, while some were positive for tyrosine hydroxylase. Thus, the ganglion was composed of a mixed population of sympathetic and parasympathetic neurons.

Oda K; Takanashi Y; Katori Y; Fujimiya M; Murakami G; Kawase T

2013-05-01

140

Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerve regeneration and after tumorigenic challenge.  

UK PubMed Central (United Kingdom)

The number of Schwann cells is fitted to axonal length in peripheral nerves. This relationship is lost when tumorigenic stimuli induce uncontrolled Schwann cell proliferation, generating tumours such us neurofibromas and schwannomas. Schwann cells also re-enter the cell cycle following nerve injury during the process of Wallerian degeneration. In both cases proliferation is finally arrested. We show that in neurofibroma, the induction of Jmjd3 (jumonji domain containing 3, histone lysine demethylase) removes trimethyl groups on lysine-27 of histone-H3 and epigenetically activates the Ink4a/Arf-locus, forcing Schwann cells towards replicative senescence. Remarkably, blocking this mechanism allows unrestricted proliferation, inducing malignant transformation of neurofibromas. Interestingly, our data suggest that in injured nerves, Schwann cells epigenetically activate the same locus to switch off proliferation and enter the senescence programme. Indeed, when this pathway is genetically blocked, Schwann cells fail to drop out of the cell cycle and continue to proliferate. We postulate that the Ink4a/Arf-locus is expressed as part of a physiological response that prevents uncontrolled proliferation of the de-differentiated Schwann cell generated during nerve regeneration, a response that is also activated to avoid overproliferation after tumorigenic stimuli in the peripheral nervous system.

Gomez-Sanchez JA; Gomis-Coloma C; Morenilla-Palao C; Peiro G; Serra E; Serrano M; Cabedo H

2013-07-01

 
 
 
 
141

Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerve regeneration and after tumorigenic challenge.  

Science.gov (United States)

The number of Schwann cells is fitted to axonal length in peripheral nerves. This relationship is lost when tumorigenic stimuli induce uncontrolled Schwann cell proliferation, generating tumours such us neurofibromas and schwannomas. Schwann cells also re-enter the cell cycle following nerve injury during the process of Wallerian degeneration. In both cases proliferation is finally arrested. We show that in neurofibroma, the induction of Jmjd3 (jumonji domain containing 3, histone lysine demethylase) removes trimethyl groups on lysine-27 of histone-H3 and epigenetically activates the Ink4a/Arf-locus, forcing Schwann cells towards replicative senescence. Remarkably, blocking this mechanism allows unrestricted proliferation, inducing malignant transformation of neurofibromas. Interestingly, our data suggest that in injured nerves, Schwann cells epigenetically activate the same locus to switch off proliferation and enter the senescence programme. Indeed, when this pathway is genetically blocked, Schwann cells fail to drop out of the cell cycle and continue to proliferate. We postulate that the Ink4a/Arf-locus is expressed as part of a physiological response that prevents uncontrolled proliferation of the de-differentiated Schwann cell generated during nerve regeneration, a response that is also activated to avoid overproliferation after tumorigenic stimuli in the peripheral nervous system. PMID:23748155

Gomez-Sanchez, Jose Antonio; Gomis-Coloma, Clara; Morenilla-Palao, Cruz; Peiro, Gloria; Serra, Eduard; Serrano, Manuel; Cabedo, Hugo

2013-06-06

142

Expression and activation of STAT3 in the astrocytes of optic nerve in a rat model of transient intraocular hypertension.  

UK PubMed Central (United Kingdom)

Lamina cribosa, an astrocyte-rich region, is the origin of axonal degeneration in glaucomatous neuropathy. Astrocytes are particularly activated during optic nerve (ON) degeneration and are likely to contribute to the pathogenesis of glaucomatous optic neuropathy. Signalling mechanisms that regulate different aspects of astrocyte reactiviation in response to intraocular hypertensive injury are not well defined. Signal transducer and activator of transcription protein-3 (STAT3) is a transcription factor that participates in many biological processes and has been implicated as activator of reactive astrogliosis. In this study, we investigated the role of STAT3 in regulating the activation of astrocytes to transient intraocular hypertension in vivo by using a rat ocular hypertension model. ON astrocytes hypertrophy was observed early after intraocular hypertensive stress. Morphological changes in glial fibrillary acidic protein (GFAP) positive cells coupled with axon loss in the optic nerve was detected at day 7 after the injury. Nestin was significantly upregulated in ON astrocytes as early as day 2 post injury and kept elevated through post injury day 7. Phosphorylated STAT3 (pSTAT3) was markedly upregulated in ON astrocytes at post injury day 1, prior to the reactivation of ON astrocytes. These findings indicate that STAT3 signalling is involved in the initiation of astrocyte reactivation in optic nerve injury.

Zhang S; Li W; Wang W; Zhang SS; Huang P; Zhang C

2013-01-01

143

Differential nerve blocking activity of amino-ester local anaesthetics.  

Science.gov (United States)

The in vitro sensitivities to local anaesthetic blockade of A, B and C nerve fibres in rabbit vagus nerves were examined using a series of structurally similar amino-ester agents which varied in lipid solubility and anaesthetic potency. A fibres were found to be the most sensitive and C fibres the least sensitive to conduction blockade with all the agents, provided that equilibrium blockade was allowed to develop. A correlation existed between the intrinsic anaesthetic potency of the various agents and their lipid solubilities. Equipotent concentrations of the drugs blocked C fibres at approximately the same rate, but there were marked variations in the rate at which A fibres were blocked. Amethocaine, an agent of high lipid solubility, blocked A fibres more quickly than C. As lipid solubility decreased through the series studied, so the onset of conduction blockade of A fibres was prolonged. It is suggested that this related to decreasing ability to penetrate the lipid diffusion barriers around A fibres. The traditional view that C fibres were more sensitive to block may have arisen because of confusion between absolute sensitivity and rate of development of conduction blockade. PMID:4005099

Wildsmith, J A; Gissen, A J; Gregus, J; Covino, B G

1985-06-01

144

Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats.  

Science.gov (United States)

The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity. PMID:22705582

da Silva Mattos, Alexandro Márcio; Xavier, Carlos Henrique; Karlen-Amarante, Marlusa; da Cunha, Natália Veronez; Fontes, Marco Antonio Peliky; Martins-Pinge, Marli Cardoso

2012-06-15

145

Nerve growth factor-mediated regulation of low density lipoprotein receptor-related protein promoter activation.  

UK PubMed Central (United Kingdom)

The mechanisms by which nerve growth factor (NGF) increases the level of low density lipoprotein receptor-related protein (LRP1) are not known. Administration of nitric oxide synthase (NOS) inhibitors modulates several of the neurotrophic actions of NGF, including TrkA signalling pathway activation, increases in gene expression and neurite outgrowth. The present study investigated whether NGF regulates the transcription of LRP1 as well as the role of NO and the individual TrkA signalling pathways in this action of NGF. PC12 cells were transfected with luciferase reporter constructs containing various sized fragments of the LRP1 promoter and treated with NGF (50 ng/mL) to establish whether NGF altered LRP transcription. NGF significantly increased luciferase activity in all LRP1 promoter construct-transfected cells with the NGF-responsive region of the promoter identified to be present in the first 1000 bp. The non-selective NOS inhibitor N(?)-nitro-L-arginine methylester (L-NAME; 20 mM) had no effect on the NGF-mediated increase in luciferase activity, while the inducible NOS selective inhibitor s-methylisothiourea (S-MIU; 2 mM) attenuated the NGF-induced activation of the LRP1 promoter. Pretreatment of PC12 cells with 10 ?M bisindolylmaleimide 1 (BIS-1) prevented the NGF-mediated increase in LRP1 promoter activation while 50 ?M U0126 partially inhibited this response. In combination with S-MIU, all of the TrkA signalling pathway inhibitors blocked the ability of NGF to increase LRP1 transcription. These data suggest the NGF-mediated increase in LRP1 levels occurs, at least in part, at the level of transcription and that NO and the TrkA signalling pathways cooperate in the modulation of LRP1 transcription.

Grana TR; LaMarre J; Kalisch BE

2013-03-01

146

[Microtubules in the nerve cells: morphological and functional aspects].  

Science.gov (United States)

The modern literature concerning ultrastructure and cytochemistry of microtubules in the nervous tissue is reviewed. Common features of cytological and biochemical organization of microtubules in different parts of the nervous system of the vertebrates and invertebrates are analysed: the similarity of ultrastructure of microtubules and their molecular organization (tubulin and its alpha- and beta-monomeres), the ability of microtubules to assemble and disassemble, to bind specifically with poisons--colchicine and vinblastine, participation of microtubules in the neuroplastic transport. The authors' data on space arrangement of microtubules within cytoplasm of the neuronal processes (dendrites and unmyelinated axons in the central and peripheral nevous system) are presented. Some literature and personal results concerning ultrastructure of neurofilaments and microtubules in the myelinated nerve fibres are also considered. The functional significance of microtubules in the nervous system is discussed with special reference to facts and hypotheses on a possible role of microtubules in the propagation of nerve impulse. PMID:7447728

Vorob'ev, V S; Portuganov, V V

1980-10-01

147

[Microtubules in the nerve cells: morphological and functional aspects  

UK PubMed Central (United Kingdom)

The modern literature concerning ultrastructure and cytochemistry of microtubules in the nervous tissue is reviewed. Common features of cytological and biochemical organization of microtubules in different parts of the nervous system of the vertebrates and invertebrates are analysed: the similarity of ultrastructure of microtubules and their molecular organization (tubulin and its alpha- and beta-monomeres), the ability of microtubules to assemble and disassemble, to bind specifically with poisons--colchicine and vinblastine, participation of microtubules in the neuroplastic transport. The authors' data on space arrangement of microtubules within cytoplasm of the neuronal processes (dendrites and unmyelinated axons in the central and peripheral nevous system) are presented. Some literature and personal results concerning ultrastructure of neurofilaments and microtubules in the myelinated nerve fibres are also considered. The functional significance of microtubules in the nervous system is discussed with special reference to facts and hypotheses on a possible role of microtubules in the propagation of nerve impulse.

Vorob'ev VS; Portuganov VV

1980-10-01

148

Alteration by estrogen of the nucleoli in nerve cells of the rat hypothalamus  

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Estrogen is accumulated from the blood by nerve cells in the ventromedial nucleus of the hypothalamus and can facilitate female reproductive behavior by acting on this region of the brain. This cell group was examined in ovariectomized female rats, given estrogen or control treatment, by use of ligh...

Cohen, RS; Chung, SK; Pfaff, DW

149

[Effect of extract of Lycium barbarum L. on adult human retinal nerve cells].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To study possible protective effects of extract of Lycium barbarum L. on the cultured human retinal nerve cells. METHODS: Retinal nerve cells were co-cultured with the extract of Lycium barbarum L. and 24 hours and 72 hours later, retinal nerve cells were respectively used to evaluate cell proliferation with MTT assays; to observe ultracellular structural alternation with transmission electron microscopy (TEM) and to evaluate mitochondrial membrane potentials (MMP) of cells with confocal microscopy. The peaks of MMP between experiment group and control group were compared using one-way analysis of variance. RESULTS: Co-cultured retinal nerve cells with the extract were shown survival well under the TEM including photoreceptor segments remaining well, abundant mitochondria in inner segments and well-distributed chromatin in photoreceptor nucleus (F = 124.110, P < 0.05). The addition of the extract promoted survival of adult retinal neurons significantly in concentration-dependent manner with the strongest effect in 20 g/L. Cell survival rate (24 h and 72 h); (223.23 ± 12.13)% and (252.35 ± 13.24)%. The peak of MMP increased 848% after the first adding of the extract (P = 0.000) and 1152% after the second adding of the extract (P = 0.000). It showed that the extract could enhance the MMP significantly with undulatory property. CONCLUSIONS: The extract of Lycium barbarum L. showed protective effects on cultured cells and could be used in treatment of some retinal diseases in future.

Shen ZJ; Wang JJ; Li GL

2012-09-01

150

Novel method for culturing Schwann cells from adult mouse sciatic nerve in vitro.  

UK PubMed Central (United Kingdom)

Schwann cells (SCs) are important in the recovery of peripheral nerve injury and are valuable cells for the tissue engineering of artificial neurons. Clinical applications that require pure SCs in large quantities are limited since human and mouse SCs do not attach well to the wall of the culture dish and have low proliferative potential. To obtain high quantities of highly pure SCs, we developed a new method for culturing SCs from the mouse sciatic nerve in vitro. Approximately 1.5 cm of the bilateral sciatic nerve of a c57 adult mouse was surgically removed and pre-cultured in DMEM containing either 10% FBS or growth factors. One week later, the in vitro SC culture was observed using light microscopy following enzyme digestion. Cell numbers and cell attachment were examined. The purity of the SCs was determined using s100? and p75NTR staining. Sciatic nerves that had not been pre-cultured were used as the control group. When the excised tissue was pre-cultured in vitro, high yields of SCs were obtained. The SCs were more likely to adhere and the purity was approximately 98% at the p1 generation following simple purification steps, which was significantly higher than the purity obtained from the control group. The pre-culturing of the sciatic nerve prior to in vitro tissue culturing significantly increased the quantity and quality of the SCs.

Wang HB; Wang XP; Zhong SZ; Shen ZL

2013-02-01

151

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

Science.gov (United States)

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.

Langert, Kelly A.; Von Zee, Cynthia L.; Stubbs, Evan B.

2013-01-01

152

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

UK PubMed Central (United Kingdom)

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.

Langert KA; Von Zee CL; Stubbs EB Jr

2013-01-01

153

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

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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.

Kelly A. Langert; Cynthia L. Von Zee; Evan B. Stubbs

2013-01-01

154

Effect of an intraduodenal injection of fat on the activities of the adrenal efferent sympathetic nerve and the gastric efferent parasympathetic nerve in urethane-anesthetized rats.  

UK PubMed Central (United Kingdom)

Nutrient information from the gastrointestinal tract to the brain plays a critical role in the regulation of appetite and energy homeostasis. The autonomic nervous system controls the functions of several tissues to regulate the energy homeostasis of the whole body. Autonomic nerve activity is influenced by environmental or exogenous changes in even a single tissue. In the present study, we investigated the effect of an intraduodenal injection of fat on the activities of the autonomic nerves innervating the adrenal gland and stomach in urethane-anesthetized rats. An intraduodenal injection of corn oil suppressed adrenal efferent sympathetic nerve activity (ASNA) and stimulated gastric efferent vagal nerve activity (GVNA). A lipase inhibitor, epsilon-polylysine, coinjected with corn oil completely suppressed the corn oil-induced changes in ASNA and GVNA. Further, an intraduodenal injection of fatty acid (linoleic acid) moderately suppressed ASNA and significantly stimulated GVNA; these results indicate that fat may affect autonomic nerve activity partly through the chemoreception of free fatty acids (FFAs), which are produced during the hydrolysis of fat (corn oil) by a pancreatic lipase, in the intestinal lumen. Furthermore, an intraduodenal injection of an intravenous fat emulsion with the same pH and osmotic pressure as the body fluid affected ASNA and GVNA in a similar manner as corn oil. These results suggest that intraduodenal fat suppresses ASNA and stimulates GVNA partly via the chemoreception of FFAs-the degradation products of fats-in the intestinal lumen.

Matsumura S; Eguchi A; Kitabayashi N; Tanida M; Shen J; Horii Y; Nagai K; Tsuzuki S; Inoue K; Fushiki T

2010-07-01

155

Effect of an intraduodenal injection of fat on the activities of the adrenal efferent sympathetic nerve and the gastric efferent parasympathetic nerve in urethane-anesthetized rats.  

Science.gov (United States)

Nutrient information from the gastrointestinal tract to the brain plays a critical role in the regulation of appetite and energy homeostasis. The autonomic nervous system controls the functions of several tissues to regulate the energy homeostasis of the whole body. Autonomic nerve activity is influenced by environmental or exogenous changes in even a single tissue. In the present study, we investigated the effect of an intraduodenal injection of fat on the activities of the autonomic nerves innervating the adrenal gland and stomach in urethane-anesthetized rats. An intraduodenal injection of corn oil suppressed adrenal efferent sympathetic nerve activity (ASNA) and stimulated gastric efferent vagal nerve activity (GVNA). A lipase inhibitor, epsilon-polylysine, coinjected with corn oil completely suppressed the corn oil-induced changes in ASNA and GVNA. Further, an intraduodenal injection of fatty acid (linoleic acid) moderately suppressed ASNA and significantly stimulated GVNA; these results indicate that fat may affect autonomic nerve activity partly through the chemoreception of free fatty acids (FFAs), which are produced during the hydrolysis of fat (corn oil) by a pancreatic lipase, in the intestinal lumen. Furthermore, an intraduodenal injection of an intravenous fat emulsion with the same pH and osmotic pressure as the body fluid affected ASNA and GVNA in a similar manner as corn oil. These results suggest that intraduodenal fat suppresses ASNA and stimulates GVNA partly via the chemoreception of FFAs-the degradation products of fats-in the intestinal lumen. PMID:20362017

Matsumura, Shigenobu; Eguchi, Ai; Kitabayashi, Nobuhide; Tanida, Mamoru; Shen, Jiao; Horii, Yuko; Nagai, Katsuya; Tsuzuki, Satoshi; Inoue, Kazuo; Fushiki, Tohru

2010-03-31

156

Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated NGF  

International Nuclear Information System (INIS)

[en] Previous studies of liposome targeting have concentrated on immunological systems, the use of ligand-receptor interactions has received little attention. The protein hormone beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated through amino group substitution to produce derivatives with ratios of 1, 2 and 4 biotin moieties per NGF subunit (N-bio-NGF). These derivatives were compared with native NGF for their ability to compete with 125I-NGF for binding to NGF receptors on rat pheochromocytoma (PC 12) cells at 40C. C-bio-NGF was as effective as native NGF in binding to NGF receptors, while N-bio-NGF containing 1 biotin per NGF subunit was only 28% as active in binding as native NGF. C-bio-NGF, but not N-bio-NGF, mediated the specific binding of 125I-streptavidin to PC12 cells. Biocytin-NGF, a derivative of C-bio-NGF with an extended spacer chain, was also synthesized and retained full biological and receptor binding activities. C-bio-NGF and biocytin-NGF were as effective as native NGF in a bioassay involving induction of neurite outgrowth from PC12 cells

1986-01-01

157

Axon outgrowth along segmental nerves in the leech. II. Identification of actual guidance cells  

Energy Technology Data Exchange (ETDEWEB)

Some peripheral neurons, previously identified as candidate guidance cells for axonal outgrowth along the segmental nerves in embryos of the glossiphoniid leech Helobdella triserialis, were photoablated by laser illumination to ascertain whether their presence is necessary for generation of the normal axonal growth pattern. These experiments showed that focal photoablation of peripheral neurons nz3 or pz8 prevents normal axonal outgrowth along the ultraposterior nerve path or along the distal sector of the medial-anterior nerve path, respectively, in conformance with the inference that these two neurons do function as guidance cells. However, ablation of these neurons affects axon outgrowth only if the neurons are illuminated prior to the end of a sensitive period in segmental development. By contrast, photoablation of previously identified candidate guidance cells situated on the anterior-anterior and posterior-posterior nerve paths, among them peripheral neurons nz1, nz2, oz1, oz2, pz6, and LD1, does not prevent normal axonal outgrowth. It is possible that the guidance role, if any, of these neurons is facultative rather than necessary, since each of the several neurons that lies on either of these nerve paths may provide an alternative axon guidance cue.

Braun, J.; Stent, G.S.

1989-04-01

158

Lacrimal gland and perioptic nerve lesions due to Langerhans cell histiocytosis (2007: 9b)  

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We report a patient presenting with bilateral lacrimal gland involvement and perioptic nerve sheath lesions due to Langerhans cell histiocytosis (LCH) invasion. LCH is a rare multisystemic disease characterized by a clonal proliferation of Langerhans cells. All organs may be involved with a clinical spectrum ranging from a solitary bone lesion to a severe life-threatening multisystem disease. Osteolytic orbital bone lesions with extension into the adjacent orbital soft tissues have been described. To our knowledge, lacrimal gland involvement has probably been described only once before. Perioptic nerve lesions are also very rare, having been described only three times before. (orig.)

Herman, M.; Demaerel, P.; Wilms, G. [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Gool, S. van [University Hospitals Leuven, Department of Pediactrics, Leuven (Belgium); Casteels, I. [University Hospitals Leuven, Department of Ophthalmology, Leuven (Belgium)

2007-12-15

159

Lacrimal gland and perioptic nerve lesions due to Langerhans cell histiocytosis (2007: 9b)  

International Nuclear Information System (INIS)

We report a patient presenting with bilateral lacrimal gland involvement and perioptic nerve sheath lesions due to Langerhans cell histiocytosis (LCH) invasion. LCH is a rare multisystemic disease characterized by a clonal proliferation of Langerhans cells. All organs may be involved with a clinical spectrum ranging from a solitary bone lesion to a severe life-threatening multisystem disease. Osteolytic orbital bone lesions with extension into the adjacent orbital soft tissues have been described. To our knowledge, lacrimal gland involvement has probably been described only once before. Perioptic nerve lesions are also very rare, having been described only three times before. (orig.)

2007-01-01

160

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

Energy Technology Data Exchange (ETDEWEB)

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

Imamura, Yoshihiro; Fukuyama, Takaya [Matsuyama Red Cross Hospital (Japan)

1997-06-01

 
 
 
 
161

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)

[en] 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

1983-11-04

162

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

UK PubMed Central (United Kingdom)

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 histopathological examination of pituitary gland biopsies, lesions were compatibles with a sellar germ cell tumor. CONCLUSION: Although they are most often of a congenital nature, third cranial nerve palsies in childhood may be secondary to other causes that should be always taken in mind. When they are secondary to a sellar tumor and according to the clinical presentation and the IRM, the histopahological examination of biopsies is mandatory to have a precise diagnosis.

Kalenga M; Collignon N; Andris C; Deprez M; Otto B

2011-01-01

163

Can Cl- ions be extruded from a gamma-aminobutyric (GABA)-acceptive nerve cell via GABAA receptors on the plasma membrane cytoplasmic side?  

Science.gov (United States)

1. In this commentary we discuss results obtained by a micromethod for the study of Cl- permeability across single nerve membranes from rabbit Deiters' neurons. 2. These results showed the presence of GABAA receptors on the nerve cell membrane cytoplasmic side. 3. We could show that these receptor complexes have a higher affinity for GABA than their extracellularly facing counterparts. Moreover, they present a phenomenon of desensitization. Another distinct property is that upon activation by GABA, they expose positive charges at their cytoplasmic mouths. 4. We propose that these receptor complexes could function in situ as a device for extruding Cl- anions from the nerve cell interior. This phenomenon would create an electrochemical gradient for Cl- penetration into the cell upon the action of extracellular GABA, after its presynaptic release. PMID:1651163

Cupello, A; Palm, A; Rapallino, M V; Hydén, H

1991-06-01

164

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

UK PubMed Central (United Kingdom)

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

Kishi T; Hirooka Y; Konno S; Sunagawa K

2009-05-01

165

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

Science.gov (United States)

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

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

2009-05-01

166

Sympathetic nerve activity is decreased during device-guided slow breathing.  

UK PubMed Central (United Kingdom)

It is known that slow breathing (<10 breaths min(-1)) reduces blood pressure (BP), but the mechanisms involved in this phenomenon are not completely clear. The aim of this study was to evaluate the acute responses of the muscle sympathetic nerve activity, BP and heart rate (HR), using device-guided slow breathing (breathe with interactive music (BIM)) or calm music. In all, 27 treated mild hypertensives were enrolled. Muscle sympathetic nerve activity, BP and HR were measured for 5 min before the use of the device (n=14) or while subjects listened to calm music (n=13), it was measured again for 15 min while in use and finally, 5 min after the interventions. BIM device reduced respiratory rate from 16+/-3 beats per minute (b.p.m) to 5.5+/-1.8 b.p.m (P<0.05), calm music did not affect this variable. Both interventions reduced systolic (-6 and -4 mm Hg for both) and diastolic BPs (-4 mm Hg and -3 mm Hg, respectively) and did not affect the HR (-1 and -2 b.p.m respectively). Only the BIM device reduced the sympathetic nerve activity of the sample (-8 bursts min(-1)). In conclusion, both device-guided slow breathing and listening to calm music have decreased BP but only the device-guided slow breathing was able to reduce the peripheral sympathetic nerve activity.

Oneda B; Ortega KC; Gusmão JL; Araújo TG; Mion D Jr

2010-07-01

167

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

UK PubMed Central (United Kingdom)

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.

Nakajima M; Tsuruta M; Mori H; Nishikawa C; Okuyama S; Furukawa Y

2013-03-01

168

Bone marrow stem cells in facial nerve regeneration from isolated stumps.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Severe lesions in the facial nerve may have extensive axonal loss and leave isolated stumps that impose technical difficulties for nerve grafting. Methods: We evaluated bone marrow stem cells (BMSC) in a silicone conduit for rat facial nerve regeneration from isolated stumps. Group A utilized empty silicone tubes; in groups B-D, the tube was filled with acellular gel; and, in groups C and D, undifferentiated BMSC (uBMSC) or Schwann-like cells differentiated from BMSC (dBMSC) were added, respectively. Compound muscle action potentials (CMAPs) were measured, and histology was evaluated. Results: Groups C and D had the highest CMAP amplitudes. Group C had shorter CMAP durations than groups A, B, and D. Distal axonal number and density were increased in group C compared with groups A and B. Conclusions: Regeneration of the facial nerve was improved by both uBMSC and dBMSC in rats, yet uBMSC was associated with superior functional results. Muscle Nerve 48: 423-429, 2013.

Salomone R; Bento RF; Costa HJ; Azzi-Nogueira D; Ovando PC; Da-Silva CF; Zanatta DB; Strauss BE; Haddad LA

2013-09-01

169

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-Timmemi Hameed; R. Ibrahim; Al-Jashamy Karim; Abz Zuki; Ti. Azmi; R. Ramasamy

2011-01-01

170

Changes in the BAG1 expression of Schwann cells after sciatic nerve crush.  

UK PubMed Central (United Kingdom)

Bcl-2-associated athanogene-1 (BAG1), a co-chaperone for Hsp70/Hsc70, is a multifunctional protein, which has been shown to suppress apoptosis and enhance neuronal differentiation. However, the expression and roles of BAG1 in peripheral system lesions and repair are still unknown. In this study, we investigated the dynamic changes in BAG1 expression in an acute sciatic nerve crush model in adult rats. Western blot analysis revealed that BAG1 was expressed in normal sciatic nerves. BAG1 expression increased progressively after sciatic nerve crush, reached a peak 2 weeks post-injury, and then returned to the normal level 4 weeks post-injury. Spatially, we observed that BAG1 was mainly expressed in Schwann cells and that BAG1 expression increased in Schwann cells after injury. In vitro, we found that BAG1 expression increased during the cyclic adenosine monophosphate (cAMP)-induced Schwann cell differentiation process. BAG1-specific siRNA inhibited cAMP-induced Schwann cell differentiation. In conclusion, we speculated that BAG1 was upregulated in the sciatic nerve after crush, which was associated with Schwann cell differentiation.

Wu H; Liu Y; Zhou Y; Long L; Cheng X; Ji L; Weng H; Ding T; Yang J; Wei H; Li M; Huan W; Deng X; Wang Y

2013-03-01

171

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.

1984-01-01

172

Selective recording of neuroelectric activity from the peripheral nerve.  

UK PubMed Central (United Kingdom)

Electroneurograms (ENGs) from superficial regions of the sciatic nerve of a dog, innervating the tibialis anterior (TA) and gastrocnemius muscles (GM), arising mainly from muscle spindles and Golgi tendon organs were recorded selectively with an implanted 33-electrode spiral cuff (cuff). Relative positions of superficial regions within the cuff were defined by delivering stimulating pulses on groups of three electrodes (GTEs) within the cuff which were in contact with them. It was found that GTEs eliciting maximum contractions of muscles were GTE No. 3 for the TA muscle and GTE No. 8 for the GM muscle. In the first experiment the implanted leg was mounted into a special electronic brace. Extending forces were applied to the ankle rotating it by up to +/-37 degrees according to the neutral position, thus eliciting torques in the TA muscle of up to 1.2 Nm. Channel 1 of the 4-channel preamplifier was connected to GTE No. 8, channel 2 to GTE No. 2, channel 3 to GTE No. 11 and channel 4 to GTE No. 5. Results show that only ENG recorded with GTE No. 8, being close to the region innervating the TA muscle, correspond to the mechanical load. In the second experiment the calcanean tendon (CT) of an implanted leg was dissected. The proximal end of the CT was connected to a force transducer and repetitive pull forces (about 12 N) were applied to the CT. Channel 1 of the preamplifier was connected to GTE No. 5, channel 2 to GTE No. 1, channel 3 to the GTE No. 11 and channel 4 to GTE No. 8. Results show that only ENG recorded with GTE No. 5, being close to the region innervating the GM muscle, correspond to the mechanical load applied on CT.

Rozman J; Zorko B; Seliskar A; Bunc M

2000-01-01

173

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity.  

Science.gov (United States)

Dihydropyridine-type calcium channel blockers (CCBs) exert potent antihypertensive effects. The CCB azelnidipine decreases heart rate by suppressing sympathetic nerve activity, which affects afferent and efferent arterioles in the glomeruli. We examined whether azelnidipine can improve progressive glomerular injury in comparison with amlodipine by suppressing renal sympathetic nerve activity in Dahl salt-sensitive rats. Glomerular circulation in Dahl salt-sensitive rats was monitored with a charge-coupled device camera before and after administration of amlodipine (0.5?mg?kg(-1), bolus injection) or azelnidipine (0.1?mg?kg(-1), bolus injection). Systemic sympathetic nerve activity was also compared by analysis of heart rate variability with a telemetry blood pressure monitoring system after crossover administration of amlodipine (1.0?mg?kg(-1) per day) and azelnidipine (3.0?mg?kg(-1) per day) for 1 week. To investigate renoprotective effects, rats were treated with amlodipine (1.0?mg?kg(-1) per day) or azelnidipine (3.0?mg?kg(-1) per day) for 3 weeks with or without renal denervation. The efferent arteriole contracted in response to acute amlodipine but not azelnidipine treatment. The low frequency/high frequency ratio, an index of parasympathetic nerve activity, decreased in response to azelnidipine but not amlodipine treatment. In response to chronic treatment, proteinuria and glomerular injury improved to a greater extent with azelnidipine compared with amlodipine. The renoprotective effects of azelnidipine were diminished by renal denervation. Azelnidipine decreased glomerular damage in Dahl salt-sensitive rats to a greater extent than amlodipine. Azelnidipine appeared to decrease intraglomerular pressure by suppressing sympathetic nerve activity. PMID:22072106

Nagasu, Hajime; Satoh, Minoru; Fujimoto, Sohachi; Tomita, Naruya; Sasaki, Tamaki; Kashihara, Naoki

2011-11-10

174

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity.  

UK PubMed Central (United Kingdom)

Dihydropyridine-type calcium channel blockers (CCBs) exert potent antihypertensive effects. The CCB azelnidipine decreases heart rate by suppressing sympathetic nerve activity, which affects afferent and efferent arterioles in the glomeruli. We examined whether azelnidipine can improve progressive glomerular injury in comparison with amlodipine by suppressing renal sympathetic nerve activity in Dahl salt-sensitive rats. Glomerular circulation in Dahl salt-sensitive rats was monitored with a charge-coupled device camera before and after administration of amlodipine (0.5?mg?kg(-1), bolus injection) or azelnidipine (0.1?mg?kg(-1), bolus injection). Systemic sympathetic nerve activity was also compared by analysis of heart rate variability with a telemetry blood pressure monitoring system after crossover administration of amlodipine (1.0?mg?kg(-1) per day) and azelnidipine (3.0?mg?kg(-1) per day) for 1 week. To investigate renoprotective effects, rats were treated with amlodipine (1.0?mg?kg(-1) per day) or azelnidipine (3.0?mg?kg(-1) per day) for 3 weeks with or without renal denervation. The efferent arteriole contracted in response to acute amlodipine but not azelnidipine treatment. The low frequency/high frequency ratio, an index of parasympathetic nerve activity, decreased in response to azelnidipine but not amlodipine treatment. In response to chronic treatment, proteinuria and glomerular injury improved to a greater extent with azelnidipine compared with amlodipine. The renoprotective effects of azelnidipine were diminished by renal denervation. Azelnidipine decreased glomerular damage in Dahl salt-sensitive rats to a greater extent than amlodipine. Azelnidipine appeared to decrease intraglomerular pressure by suppressing sympathetic nerve activity.

Nagasu H; Satoh M; Fujimoto S; Tomita N; Sasaki T; Kashihara N

2012-03-01

175

DENDRITIC CELL ACTIVATOR  

UK PubMed Central (United Kingdom)

[PROBLEMS] To provide a method of safely and efficiently activating dendritic cells and provide a dendritic cell activator capable of presenting means for the method. [MEANS FOR SOLVING PROBLEMS] There is provided a dendritic cell activator comprising an extract from shiitake mushroom mycelia. Further, there are provided, comprising the dendritic cell activator, a pharmaceutical composition, food composition, food, beverage, etc. Still further, there is provided a method of inducing mature dendritic cells, comprising treating immature dendritic cells with the dendritic cell activator. Yet still further, there are providedmature dendritic cells obtained by the above method and a pharmaceutical composition comprising the mature dendritic cells.

MATSUI Yasunori; YUKAWA Hiroshi; TAMESADA Makoto

176

DENDRITIC CELL ACTIVATOR  

UK PubMed Central (United Kingdom)

[PROBLEMS] To provide a method of safely and efficiently activating dendritic cells and provide a dendritic cell activator capable of presenting means for the method. [MEANS FOR SOLVING PROBLEMS] There is provided a dendritic cell activator comprising an extract from Phellinus linteus. Further, there are provided, comprising the dendritic cell activator, a pharmaceutical composition, food composition, food, beverage, etc. Still further, there is provided a method of inducing mature dendritic cells, comprising treating immature dendritic cells with the dendritic cell activator. Yet still further, there are provided mature dendritic cells obtained by the above method and a pharmaceutical composition comprising the mature dendritic cells.

MATSUI Yasunori; YUKAWA Hiroshi; TAMESADA Makoto

177

Differentiated and undifferentiated adipose-derived stem cells improve function in rats with peripheral nerve gaps.  

UK PubMed Central (United Kingdom)

The effect of differentiated and undifferentiated adipose-derived stem cells on the repair of peripheral nerve gaps was studied. Adipose-derived stem cells were maintained in differentiation medium for 2 weeks. The expression of Schwann cell proteins S-100, nerve growth factor receptor (NGFR) p75 and integrin ?4 was examined by immunofluorescence staining and real time-polymerase chain reaction (real time-PCR) at the end of the differentiation period. A 10-mm gap on the left sciatic nerves of 20 Fischer rats was created and bridged with silicone tube (group I), silicone tube filled with collagen gel (group II), nerve graft (group III), silicone tube filled with adipose-derived stem cells (group IV) and silicone tube filled with differentiated adipose-derived stem cells (group V). In vitro, the positivity of differentiated adipose-derived stem cells for S-100, NGFR p75 and integrin ?4 by immunofluorescence staining was 31%, 27% and 12%, respectively. Fold changes by real time-PCR in comparison with undifferentiated cells were 48.4, 168.7 and 284.85, respectively. In vivo, a walking track analysis did not yield any statistically significant differences after 3 months postoperatively; however, after 6 months, group IV (sciatic function index (SFI) = -49.1 ± 13.1) and V (SFI = -52.6 ± 5.7) showed significant improvement compared to other groups (I: -73.3 ± 5.07, II: -79.6 ± 12.01, III: -74.8 ± 12.89) (p < 0.05). Nerve conduction velocity after 6 months was higher in groups IV (4.44 ± 0.3 mm ms(-1)), V (4.25 ± 0.3 mm ms(-1)) and III (4 ± 0.3 mm ms(-1)) than in groups I (2.5 ± 2.25 mm ms(-1)) and II (2.35 ± 1.58 mm ms(-1)) (p > 0.05). Myelin fibre density and myelinated fibre/unmyelinated fibre ratio were significantly higher in the midnerve and the distal nerve in groups IV and V (p < 0.05). These results reveal the therapeutic potential of adipose-derived stem cells in nerve reconstruction.

Orbay H; Uysal AC; Hyakusoku H; Mizuno H

2012-05-01

178

Immunologists getting nervous: neuropeptides, dendritic cells and T cell activation  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract It is increasingly recognised that the immune and nervous systems are closely integrated to optimise defence systems within the lung. In this commentary, the contribution of various neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and somatostatin to the regulation of T cell activation is discussed. These neuropeptides are released not only from nerve endings but also from inflammatory immune cells such as monocytes, dendritic cells, eosinophils and mast cells. On release they can exert both direct stimulatory and inhibitory effects on T cell activation and also indirect effects through their influence on the recruitment and activation of professional antigen-presenting dendritic cells. Neuropeptides should therefore be included in the conceptual framework of the immune regulation of T cell function by dendritic cells.

Lambrecht Bart N

2001-01-01

179

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

UK PubMed Central (United Kingdom)

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 by morphology and histology. Extracellular afferent nerve discharge was recorded from the mesenteric nerve of a 2 cm colonic segment. Subgroups were treated in vitro with the mast cell stabilizer doxantrazole (10??M) or the cyclooxygenase inhibitor naproxen (10??M). RESULTS: DSS colitis resulted in morphological and histological signs of inflammation. At baseline, peak firing was 11±2 imp s?¹ in colitis segments and 5±1 imp s?¹ in uninflamed control segments (p<0.05; mean ± SEM; each n=6). In colitis segments, afferent nerve discharge to bradykinin (0.5 ?M) was increased to 47±7 compared to 23±6 imp s?¹ in recordings from non-inflamed control tissue (p<0.05). Mechanosensitivity during luminal ramp distension (0-80 cm H?O) was increased reaching 24±5 imp s?¹ at 80 cm H?O during colitis compared to 14±2 in non-inflamed controls (p<0.05). Doxantrazole or naproxen reduced afferent discharge to bradykinin and luminal ramp distension in colitis segments to control levels. CONCLUSION: Intestinal inflammation sensitizes mesenteric afferent nerve fibers to bradykinin and mechanical stimuli. The underlying mechanism responsible for this sensitization seems to involve mast cells and prostaglandins.

Xue B; Müller MH; Li J; Pesch T; Kasparek MS; Sibaev A; Hausmann M; Rogler G; Kreis ME

2013-03-01

180

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

UK PubMed Central (United Kingdom)

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

Fu LW; Longhurst JC

2013-07-01

 
 
 
 
181

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

Science.gov (United States)

Thinly myelinated A?-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T?-T?) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32-3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 ?mol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463

Fu, Liang-Wu; Longhurst, John C

2013-05-03

182

Neuronal potentialities of cells in the optic nerve of the chicken embryo are revealed in culture.  

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Neuronal potentialities in neuroepithelial cells of the chicken embryonic optic nerve were studied in culture by using neurofilament antibodies as neuronal markers. Embryonic day-4 and -5 (E4 and E5) optic stalks were explanted in vitro. Within the first few days of culture, numerous morphologically...

Giess, M C; Cochard, P; Duprat, A M

183

Transcription initiation factor IIB involves in Schwann cell differentiation after rat sciatic nerve crush.  

UK PubMed Central (United Kingdom)

Transcription Initiation Factor IIB (TFIIB), as a general transcription factor, plays an essential role in preinitiation complex assembly and transcription initiation by recruiting RNA polymerase II to the promoter. However, its distribution and function in peripheral system lesion and repair were still unknown. Here, we investigated the spatiotemporal expression of TFIIB in an acute sciatic nerve crush model in adult rats. Western blot analysis revealed that TFIIB was expressed in normal sciatic nerve. It gradually increased, reached a peak at the seventh day after crush, and then returned to the normal level at 4 weeks. We observed that TFIIB expressed mainly increased in Schwann cells and co-localized with Oct-6. In vitro, we induced Schwann cell differentiation with cyclic adenosine monophosphate (cAMP) and found that TFIIB expression was increased in the differentiated process. TFIIB-specific siRNA inhibited cAMP-induced Schwann cell morphological change and the expression of P0. Collectively, we hypothesized peripheral nerve crush-induced upregulation of TFIIB in the sciatic nerve was associated with Schwann cell differentiation.

Yang J; Cao J; Wang Y; Xu J; Zhou Z; Gu X; Liu X; Wen H; Wu H; Cheng C

2013-03-01

184

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

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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...

Nasi, E; Tillotson, D

185

Influences of casein hydrolysate ingestion on cerebral activity, autonomic nerve activity, and anxiety.  

UK PubMed Central (United Kingdom)

This study examined the influences of the oral ingestion of casein hydrolysate from bovine milk at rest physiologically and psychologically. Eleven male university students were given a casein hydrolysate drink (H) or a maltitol drink as a control (C) in a crossover study. Just before and one hour after ingestion of each drink, the total-hemoglobin (tHb) concentrations at ten points of the prefrontal cortex to evaluate cerebral activity, and heart rate variability (HRV) to evaluate autonomic nerve activity through spectral analysis were measured as physiological indicators. The Japanese version of the State--Trait Anxiety Inventory--state anxiety (STAI-s) score was also used, as a psychological indicator. In comparison between H and C ingestion, a significant difference is observed only in tHb concentrations at one of ten points. At this point, the change in tHb concentration was lower after H ingestion compared to C ingestion. And in comparison between before and after ingestion of each drink, a significant increase in tHb concentration at two points after C ingestion, a significant increase in parasympathetic activity and decrease in sympathetic activity after H ingestion, and a significant decrease in STAI-s score in H ingestion were observed. These results suggest that ingestion of the casein hydrolysate may keep prefrontal cortex activity stable while maltitol ingestion partially increases the activity. Moreover, there is a possibility that casein hydrolysate might decrease sympathetic activity, increase parasympathetic activity, and lower anxiety. We conclude that the bovine milk casein hydrolysate may have more relaxing effects than maltitol.

Nakamura H; Iwamoto M; Washida K; Sekine K; Takase M; Park BJ; Morikawa T; Miyazaki Y

2010-01-01

186

Influences of casein hydrolysate ingestion on cerebral activity, autonomic nerve activity, and anxiety.  

Science.gov (United States)

This study examined the influences of the oral ingestion of casein hydrolysate from bovine milk at rest physiologically and psychologically. Eleven male university students were given a casein hydrolysate drink (H) or a maltitol drink as a control (C) in a crossover study. Just before and one hour after ingestion of each drink, the total-hemoglobin (tHb) concentrations at ten points of the prefrontal cortex to evaluate cerebral activity, and heart rate variability (HRV) to evaluate autonomic nerve activity through spectral analysis were measured as physiological indicators. The Japanese version of the State--Trait Anxiety Inventory--state anxiety (STAI-s) score was also used, as a psychological indicator. In comparison between H and C ingestion, a significant difference is observed only in tHb concentrations at one of ten points. At this point, the change in tHb concentration was lower after H ingestion compared to C ingestion. And in comparison between before and after ingestion of each drink, a significant increase in tHb concentration at two points after C ingestion, a significant increase in parasympathetic activity and decrease in sympathetic activity after H ingestion, and a significant decrease in STAI-s score in H ingestion were observed. These results suggest that ingestion of the casein hydrolysate may keep prefrontal cortex activity stable while maltitol ingestion partially increases the activity. Moreover, there is a possibility that casein hydrolysate might decrease sympathetic activity, increase parasympathetic activity, and lower anxiety. We conclude that the bovine milk casein hydrolysate may have more relaxing effects than maltitol. PMID:20558968

Nakamura, Hirohiko; Iwamoto, Mario; Washida, Kenji; Sekine, Kazunori; Takase, Mitsunori; Park, Bum-Jin; Morikawa, Takeshi; Miyazaki, Yoshifumi

2010-01-01

187

Regulation of nerve growth factor synthesis/secretion by catecholamine in cultured mouse astroglial cells.  

UK PubMed Central (United Kingdom)

The nerve growth factor (NGF) synthesis/secretion by cultured mouse astroglial cells was modulated by catecholamine. In quiescent cells, epinephrine (EN) and dopamine (DA) markedly increased the NGF content in the conditioned medium (CM). Conversely, EN, DA, and norepinephrine (NE) decreased the NGF content in growing cells. Cholinergic agonists, metacholine and carbamylcholine, slightly increased the NGF content in quiescent cells, but showed no effects on growing cells. Other neurotransmitters tested had no effects on either growing or quiescent cells. These results suggest that catecholamine is one of the molecules responsible for regulation of NGF synthesis/secretion in the mouse brain.

Furukawa S; Furukawa Y; Satoyoshi E; Hayashi K

1987-09-01

188

Fluorescence Activated Cell Sorting Activity  

Science.gov (United States)

This resource provides an introductory activity on fluorescence activated cell sorting (FACS). As the module states, "sorting cells is an important tool for both research and diagnosing illness." The activity covers concepts such as an overview of a FACS device, tagging specific cells with fluorescent molecules, and sorting cells. This module allows students to test their knowledge as they go.The other educational modules in this series can be found here. Instructors and students are encouraged to sign up with the Electron Technologies site here before starting to use these materials.

2012-10-08

189

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

UK PubMed Central (United Kingdom)

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.

Cobianchi S; Casals-Diaz L; Jaramillo J; Navarro X

2013-02-01

190

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

2012-11-30

191

The effect of exercise on mobilization of hematopoietic progenitor cells involved in the repair of sciatic nerve crush injury.  

UK PubMed Central (United Kingdom)

Object Mobilization of hematopoietic progenitor cells (HPCs) from bone marrow involved in the process of peripheral nerve regeneration occurs mostly through deposits of CD34(+) cells. Treadmill exercise, with either differing intensity or duration, has been shown to increase axon regeneration and sprouting, but the effect of mobilization of HPCs on peripheral nerve regeneration due to treadmill exercise has not yet been elucidated. Methods Peripheral nerve injury was induced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were categorized into 2 groups: those with and without treadmill exercise (20 m/min for 60 minutes per day for 7 days). Cytospin and flow cytometry were used to determine bone marrow progenitor cell density and distribution. Neurobehavioral analysis, electrophysiological study, and regeneration marker expression were investigated at 1 and 3 weeks after exercise. The accumulation of HPCs, immune cells, and angiogenesis factors in injured nerves was determined. A separate chimeric mice study was conducted to assess CD34(+) cell distribution according to treadmill exercise group. Results Treadmill exercise significantly promoted nerve regeneration. Increased Schwann cell proliferation, increased neurofilament expression, and decreased Schwann cell apoptosis were observed 7 days after treadmill exercise. Elevated expression of S100 and Luxol fast blue, as well as decreased numbers of vacuoles, were identified in the crushed nerve 3 weeks after treadmill exercise. Significantly increased numbers of mononuclear cells, particularly CD34(+) cells, were induced in bone marrow after treadmill exercise. The deposition of CD34(+) cells was abolished by bone marrow irradiation. In addition, deposits of CD34(+) cells in crushed nerves paralleled the elevated expressions of von Willebrand factor, isolectin B4, and vascular endothelial growth factor. Conclusions Bone marrow HPCs, especially CD34(+) cells, were able to be mobilized by low-intensity treadmill exercise, and this effect paralleled the significant expression of angiogenesis factors. Treadmill exercise stimulation of HPC mobilization during peripheral nerve regeneration could be used as a therapy in human beings.

Cheng FC; Sheu ML; Su HL; Chen YJ; Chen CJ; Chiu WT; Sheehan J; Pan HC

2013-03-01

192

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

2013-03-21

193

[Effects of a beta-adrenergic blocking drug, atenolol, on efferent renal nerve activity in rabbits (author's transl)  

UK PubMed Central (United Kingdom)

Postganglionic sympathetic nerve activity (renal nerve) decreased significantly during i.v. infusion of a beta-adrenergic blocking drug, atenolol, in anesthetized rabbits. This phenomenon, at least in part reflex in nature, may contribute to the hypotensive effect of atenolol.

Friggi A; Chevalier-Cholat AM; Bodard H

1977-09-01

194

The topography of nerve cell loss from the locus caeruleus in elderly persons.  

UK PubMed Central (United Kingdom)

A topographical analysis of nerve cell loss from the locus caeruleus in "mentally normal" old people shows cell loss to be uniformly diffuse throughout the whole nucleus with no preferential involvement of any one particular area. Such findings contrast with those of ours on Alzheimer's disease and suggest differing mechanisms underlying the cell loss of old age and Alzheimer's disease. Cell loss in Alzheimer's disease is thought to relate to primary pathogenetic events in terminal fields of cerebral cortex. In "normal" old age, cell loss may be determined by changes occurring at perikaryal level possibly in respect of the cytotoxic effects of noradrenaline degradation and neuromelanin accumulation.

Marcyniuk B; Mann DM; Yates PO

1989-01-01

195

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

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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; Ferah KIZILAY; Bar?n SELÇUK; Murat ERSÖZ; Müfit AKYÜZ

2010-01-01

196

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

2009-01-01

197

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.  

UK PubMed Central (United Kingdom)

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

de Almeida Chaves Rodrigues AF; de Lima IL; Bergamaschi CT; Campos RR; Hirata AE; Schoorlemmer GH; Gomes GN

2013-01-01

198

Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice  

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Full Text Available Abstract Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving relatively few loci. Bax was excluded as a candidate gene for this phenotype.

Li Yan; Semaan Sheila J; Schlamp Cassandra L; Nickells Robert W

2007-01-01

199

Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells.  

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TrkA is a cell surface transmembrane receptor tyrosine kinase for nerve growth factor (NGF). TrkA has an NPXY motif and kinase regulatory loop similar to insulin receptor (INSR) suggesting that NGF?TrkA signaling might overlap with insulin?INSR signaling. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Moreover, expression of TrkA kinase-inactive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF. Based on these data, we propose that TrkA participates in insulin signaling pathway in PC12 cells. PMID:23749991

Geetha, Thangiah; Rege, Shraddha D; Mathews, Salome E; Meakin, Susan O; White, Morris F; Babu, Jeganathan Ramesh

2013-06-07

200

Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells.  

UK PubMed Central (United Kingdom)

TrkA is a cell surface transmembrane receptor tyrosine kinase for nerve growth factor (NGF). TrkA has an NPXY motif and kinase regulatory loop similar to insulin receptor (INSR) suggesting that NGF?TrkA signaling might overlap with insulin?INSR signaling. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Moreover, expression of TrkA kinase-inactive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF. Based on these data, we propose that TrkA participates in insulin signaling pathway in PC12 cells.

Geetha T; Rege SD; Mathews SE; Meakin SO; White MF; Babu JR

2013-08-01

 
 
 
 
201

Brain-derived neurotrophic factor from bone marrow-derived cells promotes post-injury repair of peripheral nerve.  

UK PubMed Central (United Kingdom)

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 transplantation (BMT) were performed before the injury. We evaluated nerve function using a rotarod test, sciatic function index (SFI), and motor nerve conduction velocity (MNCV) simultaneously with histological nerve analyses by immunohistochemistry before and after the nerve injury until 8 weeks. BDNF production was examined by immunohistochemistry and mRNA analyses. After the nerve crush, the controls showed severe nerve dysfunction evaluated at 1 week. However, nerve function was gradually restored and reached normal levels by 8 weeks. By immunohistochemistry, BDNF expression was very faint before injury, but was dramatically increased after injury at 1 week in the distal segment from the crush site. BDNF expression was mainly co-localized with CD45 in BMDCs, which was further confirmed by the appearance of GFP-positive cells in the BMT study. Variant analysis of BDNF mRNA also confirmed this finding. BDNF+/- mice showed a loss of function with delayed histological recovery and BDNF+/+?BDNF+/- BMT mice showed complete recovery both functionally and histologically. These results suggested that the attenuated recovery of the BDNF+/- mice was rescued by the transplantation of BMCs and that BDNF from BMDCs has an essential role in nerve repair.

Takemura Y; Imai S; Kojima H; Katagi M; Yamakawa I; Kasahara T; Urabe H; Terashima T; Yasuda H; Chan L; Kimura H; Matsusue Y

2012-01-01

202

Brain-derived neurotrophic factor from bone marrow-derived cells promotes post-injury repair of peripheral nerve.  

Science.gov (United States)

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 transplantation (BMT) were performed before the injury. We evaluated nerve function using a rotarod test, sciatic function index (SFI), and motor nerve conduction velocity (MNCV) simultaneously with histological nerve analyses by immunohistochemistry before and after the nerve injury until 8 weeks. BDNF production was examined by immunohistochemistry and mRNA analyses. After the nerve crush, the controls showed severe nerve dysfunction evaluated at 1 week. However, nerve function was gradually restored and reached normal levels by 8 weeks. By immunohistochemistry, BDNF expression was very faint before injury, but was dramatically increased after injury at 1 week in the distal segment from the crush site. BDNF expression was mainly co-localized with CD45 in BMDCs, which was further confirmed by the appearance of GFP-positive cells in the BMT study. Variant analysis of BDNF mRNA also confirmed this finding. BDNF+/- mice showed a loss of function with delayed histological recovery and BDNF+/+?BDNF+/- BMT mice showed complete recovery both functionally and histologically. These results suggested that the attenuated recovery of the BDNF+/- mice was rescued by the transplantation of BMCs and that BDNF from BMDCs has an essential role in nerve repair. PMID:23028564

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

2012-09-19

203

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

UK PubMed Central (United Kingdom)

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

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

1990-07-01

204

Nerve grafting.  

UK PubMed Central (United Kingdom)

By avoiding tension and securing anatomical neurorrhaphy, regeneration of nerve is obtainable. When the gap exceeds a certain limit, the only way to avoid tension is the use of grafts. Experience in animal experiments and clinical practice has demonstrated that regenerating axons can cross 2 optimal suture lines much more easily than one sub-standard one. For bridging a gap autografts are used, because in autografts the fascicular pattern is preserved and its Swann cells survive. With the interfascicular technique the dissection of the nerve stumps proceeds from normal to abnormal tissues and the epineurium is resected. The coaptation must be exact so that the grafts cover the whole cross sectional area of the fascicle. All this can be achieved by the use of one 10--0 or 11--0 nylon suture. The clinical results show that in the median nerve 82%, in the ulnar 80% and in the radial nerve 92% of good functional results can be obtained. Also in brachial plexus injuries the interfascicular nerve grafting procedure opened new ways. Therefore interfascicular nerve grafting, using autografts in cases of nerve repair, where a gap may occur, currently is the method of choice.

Berger A; Millesi H

1978-06-01

205

Melatonin reduces median nerve injury-induced mechanical hypersensitivity via inhibition of microglial p38 mitogen-activated protein kinase activation in rat cuneate nucleus.  

UK PubMed Central (United Kingdom)

In this study, we examined the relationships between p38 mitogen-activated protein kinase (MAPK) activation in the cuneate nucleus (CN) and behavioral hypersensitivity after chronic constriction injury (CCI) of the median nerve. We further investigated effects of melatonin administration and pinealectomy on p38 MAPK activation and development of hypersensitivity. Using immunohistochemistry and immunoblotting, low levels of phosphorylated p38 (p-p38) MAPK were detected in CN of normal rats. As early as 1 day after CCI, p-p38 MAPK levels in the ipsilateral CN were significantly increased (1.4 ± 0.2-fold, P < 0.05), which reached a maximum at 7 days (5.1 ± 0.4-fold, P < 0.001). Double immunofluorescence labeling with cell-specific markers showed that p-p38 MAPK immunoreactive cells co-expressed OX-42, a microglia activation maker, suggesting the expression of p-p38 MAPK in microglia. Microinjection of SB203580, a p38 MAPK inhibitor, into the CN 1 day after CCI attenuated injury-induced behavioral hypersensitivity in a dose-dependent manner. Furthermore, animals received melatonin treatment at daily doses of 37.5, 75, 150, or 300 mg/kg from 30 min before until 3 days after CCI. Melatonin treatment dose-dependently attenuated p-p38 MAPK levels, release of pro-inflammatory cytokines, and behavioral hypersensitivity following CCI; conversely, pinealectomy that resulted in a reduction in endogenous melatonin levels exacerbated these effects. In conclusion, median nerve injury-induced microglial p38 MAPK activation in the CN modulated development of behavioral hypersensitivity. Melatonin supplementation eased neuropathic pain via inhibition of p38 MAPK signaling pathway; contrarily, reducing endogenous blood melatonin levels by pinealectomy promoted phosphorylation of p38 MAPK and made rats more vulnerable to nerve injury-induced neuropathic pain.

Chiang RP; Huang CT; Tsai YJ

2013-03-01

206

Impaired control of renal sympathetic nerve activity following neonatal intermittent hypoxia in rats.  

UK PubMed Central (United Kingdom)

Apneas and recurring oxygen desaturations can occur in preterm infants and young children. To investigate long-term effects of neonatal intermittent hypoxia on baroreflex control of sympathetic nerve activity, we studied 5-7-month-old (adult) Sprague-Dawley rats exposed to chronic intermittent hypoxia (CIH, n=9; 8% O2 for 90 s alternating with 90 s 21% O2, 12h/day) for their first 30 postnatal days or controls exposed to normoxia (C, n=9). In adult CIH and C rats, baseline heart rate, mean arterial pressure, and plasma concentration of epinephrine and norepinephrine were similar. Baroreflex sensitivity was evaluated in anesthetized rats by changes in renal sympathetic nerve activity (RSNA) in response to i.v. infusions of phenylephrine (PE,1.5 microg/min/100g) and sodium nitroprusside (SNP, 1.5 microg/min/100g). Acute intermittent hypoxia (AIH, 18 min) induced elevations in RSNA by over 30% of baseline about three times more often in the CIH group than in the C group. After AIH, the gain of the baroreflex sympatho-excitatory response increased by approximately two times in C and did not change in CIH rats. The gain of sympatho-inhibitory responses to SNP at the maximum decrease in MAP was similar in the two groups in normoxia and was not affected by AIH. We conclude that postnatal intermittent hypoxia causes long-lasting impairment in chemoreceptor and baroreceptor control of renal nerve activity.

Soukhova-O'Hare GK; Roberts AM; Gozal D

2006-05-01

207

Impaired control of renal sympathetic nerve activity following neonatal intermittent hypoxia in rats.  

Science.gov (United States)

Apneas and recurring oxygen desaturations can occur in preterm infants and young children. To investigate long-term effects of neonatal intermittent hypoxia on baroreflex control of sympathetic nerve activity, we studied 5-7-month-old (adult) Sprague-Dawley rats exposed to chronic intermittent hypoxia (CIH, n=9; 8% O2 for 90 s alternating with 90 s 21% O2, 12h/day) for their first 30 postnatal days or controls exposed to normoxia (C, n=9). In adult CIH and C rats, baseline heart rate, mean arterial pressure, and plasma concentration of epinephrine and norepinephrine were similar. Baroreflex sensitivity was evaluated in anesthetized rats by changes in renal sympathetic nerve activity (RSNA) in response to i.v. infusions of phenylephrine (PE,1.5 microg/min/100g) and sodium nitroprusside (SNP, 1.5 microg/min/100g). Acute intermittent hypoxia (AIH, 18 min) induced elevations in RSNA by over 30% of baseline about three times more often in the CIH group than in the C group. After AIH, the gain of the baroreflex sympatho-excitatory response increased by approximately two times in C and did not change in CIH rats. The gain of sympatho-inhibitory responses to SNP at the maximum decrease in MAP was similar in the two groups in normoxia and was not affected by AIH. We conclude that postnatal intermittent hypoxia causes long-lasting impairment in chemoreceptor and baroreceptor control of renal nerve activity. PMID:16495004

Soukhova-O'Hare, Galia K; Roberts, Andrew M; Gozal, David

2006-02-21

208

Amylin acts in the central nervous system to increase sympathetic nerve activity.  

UK PubMed Central (United Kingdom)

The pancreatic hormone amylin acts in the central nervous system (CNS) to decrease food intake and body weight. We hypothesized that amylin action in the CNS promotes energy expenditure by increasing the activity of the sympathetic nervous system. In mice, ip administration of amylin significantly increased c-Fos immunoreactivity in hypothalamic and brainstem nuclei. In addition, mice treated with intracerebroventricular (icv) amylin (0.1 and 0.2 nmol) exhibited a dose-related decrease in food intake and body weight, measured 4 and 24 hours after treatment. The icv injection of amylin also increased body temperature in mice. Using direct multifiber sympathetic nerve recording, we found that icv amylin elicited a significant and dose-dependent increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT). Of note, icv injection of amylin also evoked a significant and dose-related increase in lumbar and renal SNA. Importantly, icv pretreatment with the amylin receptor antagonist AC187 (20 nmol) abolished the BAT SNA response induced by icv amylin, indicating that the sympathetic effects of amylin are receptor-mediated. Conversely, icv amylin-induced BAT SNA response was enhanced in mice overexpressing the amylin receptor subunit, RAMP1 (receptor-activity modifying protein 1), in the CNS. Our data demonstrate that CNS action of amylin regulates sympathetic nerve outflow to peripheral tissues involved in energy balance and cardiovascular function.

Fernandes-Santos C; Zhang Z; Morgan DA; Guo DF; Russo AF; Rahmouni K

2013-07-01

209

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; Jeffery D. Kocsis

2012-01-01

210

Axon-Schwann cell interaction in degenerating and regenerating peripheral nerve  

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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 P/sub 0/, the major myelin glycoprotein, and the clearance of morphological myelin. Induction of S phase was measured by determining the uptake of /sup 3/H thymidine into trichloroacetic acid (TCA) precipitates following a 3 hour in vitro incubation in Krebs-Ringers buffer containing /sup 3/H thymidine. Nerve transection stimulated a monophasic increase in /sup 3/H 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 /sup 3/H 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 /sup 3/H 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.

Pellegrino, R.G.

1984-01-01

211

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

UK PubMed Central (United Kingdom)

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.

Hassan NH; Sulong AF; Ng MH; Htwe O; Idrus RB; Roohi S; Naicker AS; Abdullah S

2012-10-01

212

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

2012-03-12

213

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; Žuni?-Božinovski Snežana; ?or?evi? D.; Vu?evi? Danijela; Nešovi?-Ostoji? Jelena

2006-01-01

214

Mouse natural killer (NK) cells express the nerve growth factor receptor TrkA, which is dynamically regulated.  

UK PubMed Central (United Kingdom)

BACKGROUND: Nerve growth factor (NGF) is a neurotrophin crucial for the development and survival of neurons. It also acts on cells of the immune system which express the NGF receptors TrkA and p75(NTR) and can be produced by them. However, mouse NK cells have not yet been studied in this context. METHODOLOGY/PRINCIPAL FINDINGS: We used cell culture, flow cytometry, confocal microscopy and ELISA assays to investigate the expression of NGF receptors by NK cells and their secretion of NGF. We show that resting NK cells express TrkA and that the expression is different on NK cell subpopulations defined by the relative presence of CD27 and CD11b. Expression of TrkA is dramatically increased in IL-2-activated NK cells. The p75(NTR) is expressed only on a very low percentage of NK cells. Functionally, NGF moderately inhibits NK cell degranulation, but does not influence proliferation or cytokine production. NK cells do not produce NGF. CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first time that mouse NK cells express the NGF receptor TrkA and that this expression is dynamically regulated.

Ralainirina N; Brons NH; Ammerlaan W; Hoffmann C; Hentges F; Zimmer J

2010-01-01

215

Low-frequency galvanic vestibular stimulation evokes two peaks of modulation in skin sympathetic nerve activity.  

UK PubMed Central (United Kingdom)

We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), delivered bilaterally at 0.2-2.0 Hz, evokes a potent entrainment of sympathetic outflow to muscle and skin. Most recently, we showed that stimulation at 0.08-0.18 Hz generates two bursts of modulation of muscle sympathetic nerve activity (MSNA), more pronounced at 0.08 Hz, which we interpreted as reflecting bilateral projections from the vestibular nuclei to the medullary nuclei responsible for the generation of MSNA. Here, we test the hypothesis that these very low frequencies of sGVS modulate skin sympathetic nerve activity (SSNA) in a similar fashion. SSNA was recorded via tungsten microelectrodes inserted into the left common peroneal nerve in 11 awake-seated subjects. Bipolar binaural sGVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.08, 0.13 and 0.18 Hz. As with MSNA, cross-correlation analysis revealed two bursts of modulation of SSNA for each cycle of stimulation but, unlike MSNA, this modulation was equally pronounced at all frequencies. These results further support our conclusion that bilateral sGVS causes cyclical modulation of the left and right vestibular nerves and a resultant modulation of sympathetic outflow that reflects the summed activity of bilateral projections from the vestibular nuclei onto, in this case, the primary output nuclei responsible for SSNA-the medullary raphé. Furthermore, these findings emphasise the role of the vestibular system in the control of skin sympathetic outflow, and the cutaneous expression of motion sickness: pallor and sweat release. Indeed, vestibular modulation of SSNA was higher in those subjects reporting nausea than in those who did not report nausea during this low-frequency sGVS.

Hammam E; Dawood T; Macefield VG

2012-06-01

216

Activation of endothelin-a receptors contributes to angiotensin-induced suppression of renal sensory nerve activation.  

Science.gov (United States)

Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosensory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized rats fed a low-sodium diet, renal pelvic administration of the Ang type I receptor (AT1-R) antagonist losartan enhanced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mm Hg from 7+/-2% to 15+/-2% and the prostaglandin (PG) E(2)-mediated substance P release from 0+/-1 to 8+/-1 pg/min. Adding the ETA-R antagonist BQ123 to the renal pelvic perfusate containing losartan did not produce any further enhancement of the ARNA response or PGE(2)-mediated release of substance P (17+/-3% and 8+/-1 pg/min). Likewise, renal pelvic administration of BQ123 and BQ123+losartan resulted in similar enhancements of the ARNA responses to increased renal pelvic pressure and PGE(2)-mediated substance P release. In high-sodium-diet rats, pelvic administration of Ang II reduced the ARNA response to increased renal pelvic pressure from 27+/-4% to 8+/-3% and the PGE(2)-mediated substance P release from 9+/-0 to 1+/-1 pg/min. Adding BQ123 to the renal pelvic perfusate containing Ang II restored the increases in ARNA and the PGE(2)-mediated substance P release toward control (27+/-6% and 7+/-1 pg/min). In conclusion, stimulation of ETA-R plays an important contributory role to the Ang II-mediated suppression of the activation of renal mechanosensory nerves in conditions of low-sodium diet. PMID:17060503

Kopp, Ulla C; Cicha, Michael Z; Smith, Lori A

2006-10-23

217

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

2012-10-27

218

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

UK PubMed Central (United Kingdom)

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.

Yosef N; Ubogu EE

2013-03-01

219

Neurosteroids: pregnenolone in human sciatic nerves.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The characterization and quantification of pregnenolone in human sciatic nerves were undertaken, following previous demonstration of the synthesis of this steroid in rat brain oligodendrocytes, to explore the hypothesis that Schwann cells may demonstrate the same biosynthetic activity. Pregnenolone ...

Morfin, R; Young, J; Corpéchot, C; Egestad, B; Sjövall, J; Baulieu, E E

220

Ictal and peri-ictal changes in cervical vagus nerve activity associated with cardiac effects.  

UK PubMed Central (United Kingdom)

The vagus nerves convey both afferent and efferent information about autonomic activity related to cardiovascular functions. Those functions have been shown to change due to epileptic seizures, which suggests that ictal events might be detected via the vagus electroneurogram (VENG). In this study, we characterize the association of ictal and peri-ictal VENG with cardiac parameters. The electrocorticogram (ECoG), electrocardiogram, and the VENG were recorded in anesthetized rats, which were intravenously infused with either a pentylenetetrazole (PTZ) solution (PTZ-lot, n = 11) or saline (control-lot, n = 6). Control animals were subsequently vagotomized and also infused with a PTZ solution (n = 5, V-PTZ-lot). Cardiac and VENG parameters were assessed during different ECoG stages of ictal activity. None of the parameters changed in the control-lot. PTZ infusion induced seizures in all rats. Cardiac-related VENG showed distinctive firing patterns for the left and right vagus nerves. Significant ictal and post-ictal changes were seen in both the left and the right VENG in association with cardiac changes and increased parasympathetic influence on the heart. Changes in VENG parameters might provide a new way to assess the ictal state of patients, which could be suitable for triggering on-demand vagus nerve stimulation.

Harreby KR; Sevcencu C; Struijk JJ

2011-09-01

 
 
 
 
221

BRAF duplications and MAPK pathway activation are frequent in gliomas of the optic nerve proper.  

UK PubMed Central (United Kingdom)

Optic pathway gliomas represent a specific subtype of astrocytoma with unique clinicopathologic and biologic properties, but studies of tumors in the optic nerve proper have been hampered by limited tissue availability. We analyzed optic nerve gliomas of 59 patients (median age, 9 years; range, 3 months-66 years; 33 female, 26 male) using formalin-fixed paraffin-embedded material in tissue microarrays. Seven patients had the clinical diagnosis of neurofibromatosis type 1 (NF1). Fluorescence in situ hybridization studies were performed for BRAF, PTEN, CDKN2A (p16), and NF1. Immunohistochemistry was performed for glial fibrillary acidic protein, phospho-ERK, and mutant IDH1 protein. The BRAF duplication was present in 11 (73%) of 15 evaluable tumors, including 1 NF1 patient (1 of 4 tested; 25%). The single tumor lacking BRAF duplication or NF1 association had histologic features of a ganglioglioma. Conversely, heterozygous PTEN deletions were present in 2 (8%) of 25 evaluable cases, one of which was BRAF duplicated and the other was NF1 associated. CDKN2A and NF1 deletions were absent in all tumors tested. Phospho-ERK immunoreactivity was present in 55 (96%) of 57 tumors and was mostly strong and diffuse (80%). Only 1 case of 53 expressed IDH1. Thus, optic nerve gliomas demonstrated molecular alterations typical of pilocytic astrocytomas, including the universal presence of either BRAF duplication or NF1 association and common mitogen-activated protein kinase pathway activation but very rare mutant IDH1 expression.

Rodriguez FJ; Ligon AH; Horkayne-Szakaly I; Rushing EJ; Ligon KL; Vena N; Garcia DI; Cameron JD; Eberhart CG

2012-09-01

222

BRAF duplications and MAPK pathway activation are frequent in gliomas of the optic nerve proper.  

Science.gov (United States)

Optic pathway gliomas represent a specific subtype of astrocytoma with unique clinicopathologic and biologic properties, but studies of tumors in the optic nerve proper have been hampered by limited tissue availability. We analyzed optic nerve gliomas of 59 patients (median age, 9 years; range, 3 months-66 years; 33 female, 26 male) using formalin-fixed paraffin-embedded material in tissue microarrays. Seven patients had the clinical diagnosis of neurofibromatosis type 1 (NF1). Fluorescence in situ hybridization studies were performed for BRAF, PTEN, CDKN2A (p16), and NF1. Immunohistochemistry was performed for glial fibrillary acidic protein, phospho-ERK, and mutant IDH1 protein. The BRAF duplication was present in 11 (73%) of 15 evaluable tumors, including 1 NF1 patient (1 of 4 tested; 25%). The single tumor lacking BRAF duplication or NF1 association had histologic features of a ganglioglioma. Conversely, heterozygous PTEN deletions were present in 2 (8%) of 25 evaluable cases, one of which was BRAF duplicated and the other was NF1 associated. CDKN2A and NF1 deletions were absent in all tumors tested. Phospho-ERK immunoreactivity was present in 55 (96%) of 57 tumors and was mostly strong and diffuse (80%). Only 1 case of 53 expressed IDH1. Thus, optic nerve gliomas demonstrated molecular alterations typical of pilocytic astrocytomas, including the universal presence of either BRAF duplication or NF1 association and common mitogen-activated protein kinase pathway activation but very rare mutant IDH1 expression. PMID:22892521

Rodriguez, Fausto J; Ligon, Azra H; Horkayne-Szakaly, Iren; Rushing, Elisabeth J; Ligon, Keith L; Vena, Natalie; Garcia, Denise I; Cameron, J Douglas; Eberhart, Charles G

2012-09-01

223

Activation of N-type calcium channels by stannous chloride at frog motor nerve terminals.  

UK PubMed Central (United Kingdom)

Stannous chloride (SnCl2) increases the calcium (Ca) entry into motor nerve terminals through the voltage-dependent Ca channels. The present study has been conducted to determine which type of channel (i.e., L-, N-, or T-type) participates in the Ca entry increased by SnCl2 (0.1 mM)-induced enhancement of the inward Ca current was more strongly inhibited by CdCl2 (50 microM) or omega-conotoxin (0.1 microM) than by NiCl2 (50 microM) or nifedipine (10 microM), respectively. From the results obtained, it is concluded that SnCl2 increases the Ca entry into the nerve terminal by activating the N-type Ca channels.

Hattori T; Maehashi H

1991-10-01

224

Improving the catalytic activity of hyperthermophilic Pyrococcus prolidases for detoxification of organophosphorus nerve agents over a broad range of temperatures.  

UK PubMed Central (United Kingdom)

Prolidase isolated from the hyperthermophilic archaeon Pyrococcus furiosus has potential for application for decontamination of organophosphorus compounds in certain pesticides and chemical warfare agents under harsh conditions. However, current applications that use an enzyme-based cocktail are limited by poor long-term enzyme stability and low reactivity over a broad range of temperatures. To obtain a better enzyme for OP nerve agent decontamination and to investigate structural factors that influence protein thermostability and thermoactivity, randomly mutated P. furiosus prolidases were prepared by using XL1-red-based mutagenesis and error-prone PCR. An Escherichia coli strain JD1 (lambdaDE3) (auxotrophic for proline [DeltaproA] and having deletions in pepQ and pepP dipeptidases with specificity for proline-containing dipeptides) was constructed for screening mutant P. furiosus prolidase expression plasmids. JD1 (lambdaDE3) cells were transformed with mutated prolidase expression plasmids and plated on minimal media supplemented with 50 muM Leu-Pro as the only source of proline. By using this positive selection, Pyrococcus prolidase mutants with improved activity over a broader range of temperatures were isolated. The activities of the mutants over a broad temperature range were measured for both Xaa-Pro dipeptides and OP nerve agents, and the thermoactivity and thermostability of the mutants were determined.

Theriot CM; Du X; Tove SR; Grunden AM

2010-08-01

225

Influence of motor activities on the release of transmitter quanta from motor nerve terminals in mice.  

UK PubMed Central (United Kingdom)

We investigated the effects of motor activities on transmitter release in mouse nerve-muscle preparations of the diaphragm muscle (DPH), extensor digitorum longus muscle (EDL), and soleus muscle (SOL). Mice were divided into a control group, a motor-restricted (RST) group, and a motor-compelled (CMP) group. The quantal content (m) of endplate potentials was measured intracellularly. In DPH the motor activity was unaffected. In the CMP group the m value of the EDL group increased with increases in the cooperativity of Ca2+ in transmitter release. Compared with the CMP group, the SOL of the RST group had a smaller m value with increases in the cooperativity of Ca2+ in transmitter release. These results suggest that motor activities can influence neuromuscular activity specific to different systems, however, the motor compulsion specifically activated the function of EDL and the motor restriction activated the function of SOL, and these effects might lead to altered activity of the release of transmitter quanta in motor nerve terminals of mice.

Taquahashi Y; Yonezawa K; Nishimura M

1999-05-01

226

[Mast cell activation syndrome].  

UK PubMed Central (United Kingdom)

BACKGROUND: The description of a monoclonal mast cell activation syndrome in patients with anaphylaxis, who fulfill one or two minor-criteria of mastocytosis, has led to a search for new unrecognized mast cell activation syndromes. OBJECTIVE: New classification of mast cell diseases including well-known diseases is provided in order to be able to better recognize and describe new entities. METHODS: The term mast cell activation has been defined by verifiable scientific objective and subjective criteria, and known and idiopathic mast cell activation syndromes have been classified. RESULTS: Mast cell activation cannot be defined by symptoms alone, as different diseases and conditions, including those with contribution of different cell types and somatization disorders may lead to similar symptoms. For this reason the preclinical checkpoint mast cell activation was defined to require typical symptoms in combination with demonstration of mast cell mediator release in (an acute) episode(s) as well as with a good response to mast cell mediator-directed therapy. Mast cell activation syndromes were classified in primary (e.g. mastocytosis), secondary (e.g. IgE-mediated allergy) and idiopathic forms. CONCLUSION: Only through a deeper understanding of mast cell diseases, can new previously unrecognized idiopathic mast cell activation syndrome entities be described and analyzed.

Brockow K

2013-02-01

227

Arterial pressure oscillation and muscle sympathetic nerve activity after 20days of head-down bed rest.  

UK PubMed Central (United Kingdom)

Both spectral power within the low-frequency component, i.e., 0.04 to 0.15Hz, of systolic pressure and muscle sympathetic nerve activity are increased during head-up tilt. The nerve activity during tilt is altered after space flight and exposure to simulated microgravity. In the present study, correlations of the low-frequency component and the nerve activity were analyzed before and after 20days of -6° of head-down bed rest. Measurements were performed at -6° head-down bed rest, 0° (flat), and 30° and 60° head-up tilt (HUT). Mean arterial pressure during HUT was not different between pre- and post-bed rest, but muscle sympathetic nerve activity in post-bed rest significantly increased at tilt angles of -6°, 0°, 30°, and 60° compared with those during pre-bed rest. The low-frequency component of systolic pressure also significantly increased during post-bed rest compared with pre-bed rest at tilts of 0°, 30°, and 60°. The nerve activity and the frequency component were linearly correlated for individual (r(2)=0.51-0.88) and averaged (r(2)=0.60) values when the values included both pre- and post-bed rest. Thus, the low-frequency component of systolic pressure could be an index of the muscle sympathetic nerve activity during tilt during pre- and post-bed rest.

Tanaka K; Nishimura N; Sato M; Kanikowska D; Shimizu Y; Inukai Y; Abe C; Iwata C; Morita H; Iwase S; Sugenoya J

2013-03-01

228

A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration.  

Science.gov (United States)

Macrophages have been implicated in peripheral nerve regeneration for some time, supposedly through their involvement in Wallerian degeneration, the process by which the distal nerve degenerates after axotomy and is cleared by phagocytosis. Thus, in several studies in which macrophage accumulation in the distal nerve was reduced and Wallerian degeneration inhibited, regeneration was delayed. However, this interpretation ignores the more recent findings that macrophages also accumulate around axotomized cell bodies. The function of macrophage action at this second site has not been clear. In two mutant strains of mice, the slow Wallerian degeneration (Wld(s)) mouse and the chemokine receptor CCR2 knock-out mouse, we report that macrophage accumulation after axotomy was abolished in both the dorsal root ganglion (DRG) and the distal sciatic nerve. To measure neurite outgrowth, DRG neurons were given a conditioning lesion, and outgrowth was measured in vitro 7 d later in the absence of the distal nerve segment. The increased growth normally seen after a conditioning lesion did not occur or was reduced in Wld(s) or CCR2(-/-) mice. In the superior cervical ganglion (SCG), particularly in Wld(s) mice, macrophage accumulation was reduced but not abolished after axotomy. In SCG neurons from Wld(s) mice, the conditioning lesion response was unchanged; however, in CCR2(-/-) mice in which the effect on macrophage accumulation was greater, SCG neurite outgrowth was significantly reduced. These results indicate that macrophages affect neurite outgrowth by acting at the level of peripheral ganglia in addition to any effects they might produce by facilitation of Wallerian degeneration. PMID:24107955

Niemi, Jon P; Defrancesco-Lisowitz, Alicia; Roldán-Hernández, Lilinete; Lindborg, Jane A; Mandell, Daniel; Zigmond, Richard E

2013-10-01

229

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

Science.gov (United States)

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

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

2002-09-01

230

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

UK PubMed Central (United Kingdom)

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

Xu X; Yu H; Gao S; Ma HQ; Leong KW; Wang S

2002-09-01

231

Mesenchymal bone marrow stem cells within polyglycolic acid tube observed in vivo after six weeks enhance facial nerve regeneration.  

Science.gov (United States)

Autografting is the gold-standard method for facial nerve repair with tissue loss. Its association with high-quality scaffolds and cell implants has disclosed distinct experimental outcomes. The aim of this study was to evaluate the functional and histological effects of bone marrow stem cells (BMSC) combined with polyglycolic acid tube (PGAt) in autografted rat facial nerves. After neurotmesis of the mandibular branch of the rat facial nerve, surgical repair consisted of nerve autografting (groups A-E) contained in pGAT (groups B-E), filled with basement membrane matrix (groups C-E) with undifferentiated BMSC (group D) or Schwann-like cells that had differentiated from BMSC (group E). Axon morphometrics and an objective compound muscle action potentials (CMAP) analysis were conducted. Immunofluorescence assays were carried out with Schwann cell marker S100 and anti-?-galactosidase to label exogenous cells. Six weeks after surgery, animals from either cell-containing group had mean CMAP amplitudes significantly higher than control groups. Differently from other groups, facial nerves with Schwann-like cell implants had mean axonal densities within reference values. This same group had the highest mean axonal diameter in distal segments. We observed expression of the reporter gene lacZ in nerve cells in the graft and distally from it in groups D and E. Group-E cells had lacZ coexpressed with S100. In conclusion, regeneration of the facial nerve was improved by BMSC within PGAt in rats, yet Schwann-like cells were associated with superior effects. Accordingly, groups D and E had BMSC integrated in neural tissue with maintenance of former cell phenotype for six weeks. PMID:23542586

Costa, Heloisa Juliana Zabeu Rossi; Ferreira Bento, Ricardo; Salomone, Raquel; Azzi-Nogueira, Deborah; Zanatta, Daniela B; Paulino Costa, Márcio; da Silva, Ciro Ferreira; Strauss, Bryan E; Haddad, Luciana A

2013-03-28

232

Mesenchymal bone marrow stem cells within polyglycolic acid tube observed in vivo after six weeks enhance facial nerve regeneration.  

UK PubMed Central (United Kingdom)

Autografting is the gold-standard method for facial nerve repair with tissue loss. Its association with high-quality scaffolds and cell implants has disclosed distinct experimental outcomes. The aim of this study was to evaluate the functional and histological effects of bone marrow stem cells (BMSC) combined with polyglycolic acid tube (PGAt) in autografted rat facial nerves. After neurotmesis of the mandibular branch of the rat facial nerve, surgical repair consisted of nerve autografting (groups A-E) contained in pGAT (groups B-E), filled with basement membrane matrix (groups C-E) with undifferentiated BMSC (group D) or Schwann-like cells that had differentiated from BMSC (group E). Axon morphometrics and an objective compound muscle action potentials (CMAP) analysis were conducted. Immunofluorescence assays were carried out with Schwann cell marker S100 and anti-?-galactosidase to label exogenous cells. Six weeks after surgery, animals from either cell-containing group had mean CMAP amplitudes significantly higher than control groups. Differently from other groups, facial nerves with Schwann-like cell implants had mean axonal densities within reference values. This same group had the highest mean axonal diameter in distal segments. We observed expression of the reporter gene lacZ in nerve cells in the graft and distally from it in groups D and E. Group-E cells had lacZ coexpressed with S100. In conclusion, regeneration of the facial nerve was improved by BMSC within PGAt in rats, yet Schwann-like cells were associated with superior effects. Accordingly, groups D and E had BMSC integrated in neural tissue with maintenance of former cell phenotype for six weeks.

Costa HJ; Ferreira Bento R; Salomone R; Azzi-Nogueira D; Zanatta DB; Paulino Costa M; da Silva CF; Strauss BE; Haddad LA

2013-05-01

233

Activation of the galanin receptor 2 in the periphery reverses nerve injury-induced allodynia  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain. Results Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord. Conclusions These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive responses.

Hulse Richard P; Wynick David; Donaldson Lucy F

2011-01-01

234

Activation of the galanin receptor 2 in the periphery reverses nerve injury-induced allodynia.  

UK PubMed Central (United Kingdom)

BACKGROUND: Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain. RESULTS: Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord. CONCLUSIONS: These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive responses.

Hulse RP; Wynick D; Donaldson LF

2011-01-01

235

[Histological picture of young and mature nerve cells in the sympathetic ganglia of coypu (Myocastor coypus Mol.)].  

Science.gov (United States)

The histological picture of the ganglion of the coypus sympathetic trunk was presented in the work. Quantitative studies of sympathicoblasts, young and immature sympathicocytes, and other intermediate cell division forms; binucleolated, binucleated and twin cells were also included in the paper. Beside young cells, the histological picture of mature nerve cells was studied and described. PMID:555515

Langenfeld, M

1979-01-01

236

[Histological picture of young and mature nerve cells in the sympathetic ganglia of coypu (Myocastor coypus Mol.)  

UK PubMed Central (United Kingdom)

The histological picture of the ganglion of the coypus sympathetic trunk was presented in the work. Quantitative studies of sympathicoblasts, young and immature sympathicocytes, and other intermediate cell division forms; binucleolated, binucleated and twin cells were also included in the paper. Beside young cells, the histological picture of mature nerve cells was studied and described.

Langenfeld M

1979-01-01

237

Attenuated baroreflex control of sympathetic nerve activity in obese Zucker rats by central mechanisms.  

Science.gov (United States)

Adult obese Zucker rats (OZRs) have reduced sympathetic responses to evoked changes in arterial pressure (AP) compared to lean Zucker rats (LZRs). This study examined whether attenuated sympathetic baroreflexes in OZRs may be due to altered sensory or central mechanisms. The OZRs had elevated baseline splanchnic sympathetic nerve activity (SNA) and mean AP (MAP) compared to age-matched LZRs under urethane anaesthesia (P ADN afferent fibres (5 s train, 2 ms pulses, 4 V, 0.5-48 Hz) produced dramatically smaller reductions in SNA and MAP in OZRs compared to LZRs (P ADN. In addition, stimulation of vagal afferent nerves electrically or with phenylbiguanide (1, 2, 4 and 8 microg, i.v.) produced smaller inhibitions of SNA in OZRs compared with LZRs (P < 0.05). These data suggest that attenuated sympathetic baroreflexes are the result of altered central mechanisms in OZRs, and not deficits in the responsiveness of aortic baroreceptors to AP. Furthermore, central deficits in the regulation of SNA in OZRs extend to other sympathoinhibitory reflexes initiated by vagal afferent nerves. PMID:20211978

Huber, Domitila A; Schreihofer, Ann M

2010-03-08

238

Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures.  

Science.gov (United States)

The vanilloid receptor subtype 1 (VR1)/(TRPV1), binding capsaicin, is a non-selective cation channel that recently has been shown in human keratinocytes in vitro and in vivo. However, a description of VR1 localization in other cutaneous compartments in particular cutaneous nerve fibers is still lacking. We therefore investigated VR1 immunoreactivity as well as mRNA and protein expression in a series (n = 26) of normal (n = 7), diseased (n = 13) [prurigo nodularis (PN) (n = 10), generalized pruritus (n = 1), and mastocytosis (n = 2)], and capsaicin-treated human skin (n = 6). VR1 immunoreactivity could be observed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands. Upon reverse transcriptase-polymerase chain reaction and Western blot analysis, VR1 was detected in mast cells and keratinocytes from human skin. In pruritic skin of PN, VR1 expression was highly increased in epidermal keratinocytes and nerve fibers, which was normalized after capsaicin application. During capsaicin therapy, a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation. PMID:14987252

Ständer, Sonja; Moormann, Corinna; Schumacher, Mark; Buddenkotte, Jörg; Artuc, Metin; Shpacovitch, Victoria; Brzoska, Thomas; Lippert, Undine; Henz, Beate M; Luger, Thomas A; Metze, Dieter; Steinhoff, Martin

2004-03-01

239

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

UK PubMed Central (United Kingdom)

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

Strong C; Yanamadala V; Khanna A; Walcott BP; Nahed BV; Borges LF; Coumans JV

2013-08-01

240

Transcutaneous electrical nerve stimulation (TENS) improves the rest-activity rhythm in midstage Alzheimer's disease.  

UK PubMed Central (United Kingdom)

Nightly restlessness in patients with Alzheimer's disease (AD) is probably due to a disorder of circadian rhythms. Transcutaneous electrical nerve stimulation (TENS) was previously reported to increase the strength of coupling of the circadian rest activity rhythm to Zeitgebers in early stage Alzheimer's disease (AD) patients. It was investigated in the present study whether TENS could also improve the rest activity rhythm of patients in a midstage. Sixteen patients who met the NINCDS ADRDA criteria for probable AD, and the stage 6 criteria of the Global Deterioration Scale were treated with TENS or placebo. Rest activity rhythm was assessed using actigraphy. Compared to the control group, stimulated patients showed an improvement in the rest activity rhythm of similar magnitude as observed previously in patients in an early stage. It is concluded that TENS increased the coupling between the rest activity rhythm and supposedly stable Zeitgebers in an advanced stage of AD.

Scherder EJ; Van Someren EJ; Swaab DF

1999-05-01

 
 
 
 
241

Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats.  

UK PubMed Central (United Kingdom)

BACKGROUND: Vagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear. METHODS: Bilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research. We studied the effects of vagus nerve stimulation (VNS) on disturbed one-way active avoidance learning and neurogenesis in the hippocampal dentate gyrus of rats. RESULTS: After a stimulation period of 3 weeks, OBX rats acquired the learning task as controls. In addition, the OBX-related decrease of neuronal differentiated BrdU positive cells in the dentate gyrus was prevented by VNS. CONCLUSIONS: This suggests that chronic VNS and changes in hippocampal neurogenesis induced by VNS may also account for the amelioration of behavioral deficits in OBX rats. To the best of our knowledge, this is the first report on the restorative effects of VNS on behavioral function in an animal model of depression that can be compared with the effects of antidepressants.

Gebhardt N; Bär KJ; Boettger MK; Grecksch G; Keilhoff G; Reichart R; Becker A

2013-01-01

242

Solar cell activation system  

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A system for activating solar cells involves the use of phosphorescent paint, the light from which is amplified by a thin magnifying lens and used to activate solar cells. In a typical system, a member painted with phosphorescent paint is mounted adjacent a thin magnifying lens which focuses the light on a predetermined array of sensitive cells such as selenium, cadmium or silicon, mounted on a plastic board. A one-sided mirror is mounted adjacent the cells to reflect the light back onto said cells for purposes of further intensification. The cells may be coupled to rechargeable batteries or used to directly power a small radio or watch.

Apelian, L.

1983-07-05

243

Bacterial Cell Surface Display of Organophosphorus Hydrolase for Selective Screening of Improved Hydrolysis of Organophosphate Nerve Agents  

Science.gov (United States)

Organophosphorus hydrolase (OPH) is a bacterial enzyme that has been shown to degrade a wide range of neurotoxic organophosphate nerve agents. However, the effectiveness of degradation varies dramatically, ranging from highly efficient with paraoxon to relatively slow with methyl parathion. Sequential cycles of DNA shuffling and screening were used to fine-tune and enhance the activity of OPH towards poorly degraded substrates. Because of the inaccessibility of these pesticides across the cell membrane, OPH variants were displayed on the surface of Escherichia coli using the truncated ice nucleation protein in order to isolate novel enzymes with truly improved substrate specificities. A solid-phase top agar method based on the detection of the yellow product p-nitrophenol was developed for the rapid prescreening of potential variants with improved hydrolysis of methyl parathion. Two rounds of DNA shuffling and screening were carried out, and several improved variants were isolated. One variant in particular, 22A11, hydrolyzes methyl parathion 25-fold faster than does the wild type. Because of the success that we achieved with directed evolution of OPH for improved hydrolysis of methyl parathion, we believe that we can easily extend this method in creating other OPH variants with improved activity against poorly degraded pesticides such as diazinon and chlorpyrifos and nerve agents such as sarin and soman.

Cho, Catherine Mee-Hie; Mulchandani, Ashok; Chen, Wilfred

2002-01-01

244

Inhibition of micturition reflex by activation of somatic afferents in posterior femoral cutaneous nerve.  

UK PubMed Central (United Kingdom)

This study determined if activation of somatic afferents in posterior femoral cutaneous nerve (PFCN) could modulate the micturition reflex recorded under isovolumetric conditions in ?-chloralose anaesthetized cats. PFCN stimulation inhibited reflex bladder activity and significantly (P <0.05) increased bladder capacity during slow infusion of saline or 0.25% acetic acid (AA). The optimal frequency for PFCN stimulation-induced bladder inhibition was between 3 and 10 Hz, and a minimal stimulation intensity of half of the threshold for inducing anal twitching was required. Bilateral pudendal nerve transection eliminated PFCN stimulation-induced anal twitching but did not change the stimulation-induced bladder inhibition, excluding the involvement of pudendal afferent or efferent axons in PFCN afferent inhibition.Mechanical or electrical stimulation on the skin surface in the PFCN dermatome also inhibited bladder activity. Prolonged (2 × 30 min) PFCN stimulation induced a post-stimulation inhibition that persists for at least 2 h. This study revealed a new cutaneous-bladder reflex activated by PFCN afferents. Although the mechanisms and physiological functions of this cutaneous-bladder reflex need to be further studied, our data raise the possibility that stimulation of PFCN afferents might be useful clinically for the treatment of overactive bladder symptoms.

Tai C; Shen B; Mally AD; Zhang F; Zhao S; Wang J; Roppolo JR; de Groat WC

2012-10-01

245

Inhibition of micturition reflex by activation of somatic afferents in posterior femoral cutaneous nerve.  

Science.gov (United States)

This study determined if activation of somatic afferents in posterior femoral cutaneous nerve (PFCN) could modulate the micturition reflex recorded under isovolumetric conditions in ?-chloralose anaesthetized cats. PFCN stimulation inhibited reflex bladder activity and significantly (P PFCN stimulation-induced bladder inhibition was between 3 and 10 Hz, and a minimal stimulation intensity of half of the threshold for inducing anal twitching was required. Bilateral pudendal nerve transection eliminated PFCN stimulation-induced anal twitching but did not change the stimulation-induced bladder inhibition, excluding the involvement of pudendal afferent or efferent axons in PFCN afferent inhibition.Mechanical or electrical stimulation on the skin surface in the PFCN dermatome also inhibited bladder activity. Prolonged (2 × 30 min) PFCN stimulation induced a post-stimulation inhibition that persists for at least 2 h. This study revealed a new cutaneous-bladder reflex activated by PFCN afferents. Although the mechanisms and physiological functions of this cutaneous-bladder reflex need to be further studied, our data raise the possibility that stimulation of PFCN afferents might be useful clinically for the treatment of overactive bladder symptoms. PMID:22869011

Tai, Changfeng; Shen, Bing; Mally, Abhijith D; Zhang, Fan; Zhao, Shouguo; Wang, Jicheng; Roppolo, James R; de Groat, William C

2012-08-06

246

Ligand activation of nerve growth factor receptor TrkA protects monocytes from apoptosis.  

UK PubMed Central (United Kingdom)

Nerve growth factor (NGF) receptors are expressed in different cell types outside the nervous system, and increasing evidence indicates that NGF can act as a regulatory molecule during inflammatory and immune responses. In this study, we show that triggering of the high-affinity NGF receptor TrkA with agonists protects monocytes from apoptosis induced by gliotoxin or UVB radiation. TrkA stimulation up-regulates the expression of the anti-apoptotic Bcl-2 family members, Bcl-2, Bcl-XL, and Bfl-1. On the other hand, TrkA stimulation does not change the expression of MHC, CD80, CD86, CD40, and CD54 molecules, nor the antigen-presenting function of monocytes. In addition, during in vitro monocyte to dendritic cell differentiation TrkA expression is progressively lost, suggesting that NGF selectively affects monocyte but not dendritic cell survival.

la Sala A; Corinti S; Federici M; Saragovi HU; Girolomoni G

2000-07-01

247

Ligand activation of nerve growth factor receptor TrkA protects monocytes from apoptosis.  

Science.gov (United States)

Nerve growth factor (NGF) receptors are expressed in different cell types outside the nervous system, and increasing evidence indicates that NGF can act as a regulatory molecule during inflammatory and immune responses. In this study, we show that triggering of the high-affinity NGF receptor TrkA with agonists protects monocytes from apoptosis induced by gliotoxin or UVB radiation. TrkA stimulation up-regulates the expression of the anti-apoptotic Bcl-2 family members, Bcl-2, Bcl-XL, and Bfl-1. On the other hand, TrkA stimulation does not change the expression of MHC, CD80, CD86, CD40, and CD54 molecules, nor the antigen-presenting function of monocytes. In addition, during in vitro monocyte to dendritic cell differentiation TrkA expression is progressively lost, suggesting that NGF selectively affects monocyte but not dendritic cell survival. PMID:10914496

la Sala, A; Corinti, S; Federici, M; Saragovi, H U; Girolomoni, G

2000-07-01

248

Remote Ischemic Postconditioning Promotes the Survival of Retinal Ganglion Cells after Optic Nerve Injury.  

UK PubMed Central (United Kingdom)

Ischemic conditioning, the application of a mild ischemic stimulus to an ischemia-sensitive structure like the heart or brain either before (preconditioning) or after (postconditioning) its exposure to a lethal ischemic insult, is known to switch on endogenous protective mechanisms. However, most studies of its neuroprotective effect in the central nervous system (CNS) have focused on ischemic damage or related conditions like hypoxia, while its potential in treating other neural diseases remains uncertain. In particular, the recent discovery of remote ischemic postconditioning whereby mild ischemia applied to a region remote from the target after the main ischemic insult also confers protection offers an attractive paradigm to study its potential in other types of neural injury. Retinal ganglion cells damaged by optic nerve transection undergo extensive cell death. However, application of a series of mild ischemic/reperfusion cycles to the hind limb (limb remote ischemic postconditioning) at 10 min or 6 h after optic nerve cut was found to promote ganglion cell survival at 7 days post-injury, with the 10 min postconditioning still exerting protection at 14 days post-injury. Concomitant with the increased ganglion cell survival, 51 % more ganglion cells expressed the small heat shock protein HSP27, when remote ischemic postconditioning was performed at 10 min post-injury, as compared to the sham conditioning group. Our results highlight the potential of using remote ischemic postconditioning as a noninvasive neuroprotective strategy in different CNS disorders like spinal cord and traumatic brain injury.

Liu X; Sha O; Cho EY

2013-06-01

249

Remote Ischemic Postconditioning Promotes the Survival of Retinal Ganglion Cells after Optic Nerve Injury.  

Science.gov (United States)

Ischemic conditioning, the application of a mild ischemic stimulus to an ischemia-sensitive structure like the heart or brain either before (preconditioning) or after (postconditioning) its exposure to a lethal ischemic insult, is known to switch on endogenous protective mechanisms. However, most studies of its neuroprotective effect in the central nervous system (CNS) have focused on ischemic damage or related conditions like hypoxia, while its potential in treating other neural diseases remains uncertain. In particular, the recent discovery of remote ischemic postconditioning whereby mild ischemia applied to a region remote from the target after the main ischemic insult also confers protection offers an attractive paradigm to study its potential in other types of neural injury. Retinal ganglion cells damaged by optic nerve transection undergo extensive cell death. However, application of a series of mild ischemic/reperfusion cycles to the hind limb (limb remote ischemic postconditioning) at 10 min or 6 h after optic nerve cut was found to promote ganglion cell survival at 7 days post-injury, with the 10 min postconditioning still exerting protection at 14 days post-injury. Concomitant with the increased ganglion cell survival, 51 % more ganglion cells expressed the small heat shock protein HSP27, when remote ischemic postconditioning was performed at 10 min post-injury, as compared to the sham conditioning group. Our results highlight the potential of using remote ischemic postconditioning as a noninvasive neuroprotective strategy in different CNS disorders like spinal cord and traumatic brain injury. PMID:23733254

Liu, Xia; Sha, Ou; Cho, Eric Y P

2013-06-01

250

Expression and activation of the nerve growth factor receptor TrkA in serous ovarian carcinoma.  

UK PubMed Central (United Kingdom)

PURPOSE: The purpose is to analyze the possible correlation between expression and activation of the high-affinity nerve growth factor (NGF) receptor TrkA, cell cycle protein expression, and disease outcome in serous ovarian carcinoma. In addition, we wished to study the possible link between expression of NGF, a novel angiogenic factor and its receptor TrkA, and the expression of factors involved in angiogenesis in effusions and solid tumors. EXPERIMENTAL DESIGN: Sections from 80 malignant effusions and 65 corresponding solid tumors were evaluated for protein expression of NGF, TrkA, and phospho-TrkA (p-TrkA). Effusions were additionally studied for expression of p53, p21(WAF1/CIP1), Ki-67, and the M(r) 85,000-cleaved fragment of poly(ADP-ribose) polymerase (p85-PARP) using immunohistochemistry (IHC). Thirty-two effusions were studied for TrkA, p-TrkA, p53, and p21(WAF1/CIP1) expression using immunoblotting. mRNA expression of basic fibroblast growth factor (bFGF), interleukin 8, and vascular endothelial growth factor (VEGF) was studied in 63 effusions and all solid tumors using in situ hybridization. Protein expression of bFGF, interleukin 8, and VEGF was additionally studied in 30 effusions using IHC. RESULTS: NGF, TrkA, and p-TrkA were expressed in carcinoma cells in effusions in 60 of 80 (75%), 64 of 80 (80%), and 15 of 80 (19%) specimens, respectively. In solid tumors, p-TrkA expression was more frequent (52 of 65 tumors; 80%) and was accompanied by p-TrkA expression in endothelial cells. NGF colocalized with bFGF protein (P = 0.016) and mRNA (P = 0.032) in effusions, and with VEGF (P < 0.001) and bFGF (P = 0.008) in solid tumors. In survival analysis, expression of p85-PARP (P = 0.017) and cytoplasmic TrkA (P < 0.001) in effusions predicted better outcome, whereas membrane expression of p-TrkA in solid tumors correlated with poor survival (P = 0.004). Diffuse expression of p53 and Ki-67 was often seen using IHC, whereas p21(WAF1/CIP1) and p85-PARP expression was infrequent and focal. None of these correlated with NGF or TrkA expression or activity. CONCLUSIONS: Coexpression of NGF with molecules involved in angiogenesis and p-TrkA expression in endothelial cells suggest that the proangiogenic role attributed to NGF in vitro and in vivo may be relevant in clinical cancer. Expression of p85-PARP as a marker of apoptosis and cytoplasmic expression of TrkA (probably representing nonglycosylated receptor) predict better outcome, whereas p-TrkA activation correlates with poor outcome in advanced stage serous ovarian carcinoma.

Davidson B; Reich R; Lazarovici P; Nesland JM; Skrede M; Risberg B; Tropé CG; Flørenes VA

2003-06-01

251

Modulation of muscle sympathetic nerve activity by low-frequency physiological activation of the vestibular utricle in awake humans.  

Science.gov (United States)

We recently showed that selective stimulation of one set of otolithic organs-those located in the utricle, sensitive to displacement in the horizontal axis-causes a marked entrainment of skin sympathetic nerve activity (SSNA). Here, we assessed whether muscle sympathetic nerve activity (MSNA) is similarly modulated. MSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in 12 awake subjects, seated (head vertical, eyes closed) on a motorised platform. Slow sinusoidal accelerations-decelerations (±4 mG) were applied in the X (antero-posterior) or Y (medio-lateral) direction at 0.08 Hz. Cross-correlation analysis revealed partial entrainment of MSNA: vestibular modulation was 32 ± 3 % for displacements in the X-axis and 29 ± 3 % in the Y-axis; these were significantly smaller than those evoked in SSNA (97 ± 3 and 91 ± 5 %, respectively). For each sinusoidal cycle, there were two peaks of modulation-one associated with acceleration as the platform moved forward or to the side and one associated with acceleration in the opposite direction. We believe the two peaks reflect inertial displacement of the stereocilia within the utricle during sinusoidal acceleration, which evokes vestibulosympathetic reflexes that are expressed as vestibular modulation of MSNA as well as of SSNA. The smaller vestibular modulation of MSNA can be explained by the dominant modulation of MSNA by the arterial baroreceptors. PMID:23852323

Hammam, Elie; Kwok, Kenny; Macefield, Vaughan G

2013-07-14

252

Nerve growth factor receptor TrkA signaling in breast cancer cells involves Ku70 to prevent apoptosis.  

UK PubMed Central (United Kingdom)

The nerve growth factor (NGF)-tyrosine kinase receptor TrkA plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation, and proliferation. In breast cancer cells, TrkA stimulation results in the activation of cellular growth, but downstream signaling largely remains to be described. Here we used a proteomics-based approach to identify partners involved in TrkA signaling in breast cancer cells. Wild type and modified TrkA chimeric constructs with green fluorescent protein were transfected in MCF-7 cells, and co-immunoprecipitated proteins were separated by SDS-PAGE before nano-LC-MS/MS analysis. Several TrkA putative signaling partners were identified among which was the DNA repair protein Ku70, which is increasingly reported for its role in cell survival and carcinogenesis. Physiological interaction of Ku70 with endogenous TrkA was induced upon NGF stimulation in non-transfected cells, and co-localization was observed with confocal microscopy. Mass spectrometry analysis and Western blotting of phosphotyrosine immunoprecipitates demonstrated the induction of Ku70 tyrosine phosphorylation upon NGF stimulation. Interestingly no interaction between TrkA and Ku70 was detected in PC12 cells in the absence or presence of NGF, suggesting that it is not involved in the initiation of neuronal differentiation. In breast cancer cells, RNA interference indicated that whereas Ku70 depletion had no direct effect on cell survival, it induced a strong potentiation of apoptosis in TrkA-overexpressing cells. In conclusion, TrkA signaling appears to be proapoptotic in the absence of Ku70, and this protein might therefore play a role in the long time reported ambivalence of tyrosine kinase receptors that can exhibit both anti- and eventually proapoptotic activities.

Com E; Lagadec C; Page A; El Yazidi-Belkoura I; Slomianny C; Spencer A; Hammache D; Rudkin BB; Hondermarck H

2007-11-01

253

Nerve growth factor receptor TrkA signaling in breast cancer cells involves Ku70 to prevent apoptosis.  

Science.gov (United States)

The nerve growth factor (NGF)-tyrosine kinase receptor TrkA plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation, and proliferation. In breast cancer cells, TrkA stimulation results in the activation of cellular growth, but downstream signaling largely remains to be described. Here we used a proteomics-based approach to identify partners involved in TrkA signaling in breast cancer cells. Wild type and modified TrkA chimeric constructs with green fluorescent protein were transfected in MCF-7 cells, and co-immunoprecipitated proteins were separated by SDS-PAGE before nano-LC-MS/MS analysis. Several TrkA putative signaling partners were identified among which was the DNA repair protein Ku70, which is increasingly reported for its role in cell survival and carcinogenesis. Physiological interaction of Ku70 with endogenous TrkA was induced upon NGF stimulation in non-transfected cells, and co-localization was observed with confocal microscopy. Mass spectrometry analysis and Western blotting of phosphotyrosine immunoprecipitates demonstrated the induction of Ku70 tyrosine phosphorylation upon NGF stimulation. Interestingly no interaction between TrkA and Ku70 was detected in PC12 cells in the absence or presence of NGF, suggesting that it is not involved in the initiation of neuronal differentiation. In breast cancer cells, RNA interference indicated that whereas Ku70 depletion had no direct effect on cell survival, it induced a strong potentiation of apoptosis in TrkA-overexpressing cells. In conclusion, TrkA signaling appears to be proapoptotic in the absence of Ku70, and this protein might therefore play a role in the long time reported ambivalence of tyrosine kinase receptors that can exhibit both anti- and eventually proapoptotic activities. PMID:17617666

Com, Emmanuelle; Lagadec, Chann; Page, Adeline; El Yazidi-Belkoura, Ikram; Slomianny, Christian; Spencer, Ambre; Hammache, Djilali; Rudkin, Brian B; Hondermarck, Hubert

2007-07-07

254

DNA Methyltransferase 3b Regulates Nerve Growth Factor-Induced Differentiation of PC12 Cells by Recruiting Histone Deacetylase 2  

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To elucidate the role of epigenetic reprogramming in cell- or tissue-specific differentiation, we explored the role of DNA methyltransferases (Dnmts) in the nerve growth factor (NGF)-induced differentiation of PC12 (pheochromocytoma) cells into neuronal cells. The mRNA and protein levels of de novo ...

Bai, Shoumei; Ghoshal, Kalpana; Datta, Jharna; Majumder, Sarmila; Yoon, Sung Ok; Jacob, Samson T.

255

Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence.  

Science.gov (United States)

Repair of large nerve defects with acellular nerve allografts (ANAs) is an appealing alternative to autografting and allotransplantation. ANAs have been shown to be similar to autografts in supporting axonal regeneration across short gaps, but fail in larger defects due to a poorly-understood mechanism. ANAs depend on proliferating Schwann cells (SCs) from host tissue to support axonal regeneration. Populating longer ANAs places a greater proliferative demand on host SCs that may stress host SCs, resulting in senescence. In this study, we investigated axonal regeneration across increasing isograft and ANA lengths. We also evaluated the presence of senescent SCs within both graft types. A sciatic nerve graft model in rats was used to evaluate regeneration across increasing isograft (~autograft) and ANA lengths (20, 40, and 60mm). Axonal regeneration and functional recovery decreased with increased graft length and the performance of the isograft was superior to ANAs at all lengths. Transgenic Thy1-GFP rats and qRT-PCR demonstrated that failure of the regenerating axonal front in ANAs was associated with increased levels of senescence related markers in the graft (senescence associated ?-galactosidase, p16(INK4A), and IL6). Lastly, electron microscopy (EM) was used to qualitatively assess senescence-associated changes in chromatin of SCs in each graft type. EM demonstrated an increase in the presence of SCs with abnormal chromatin in isografts and ANAs of increasing graft length. These results are the first to suggest that SC senescence plays a role in limited axonal regeneration across nerve grafts of increasing gap lengths. PMID:23644284

Saheb-Al-Zamani, Maryam; Yan, Ying; Farber, Scott J; Hunter, Daniel A; Newton, Piyaraj; Wood, Matthew D; Stewart, Sheila A; Johnson, Philip J; Mackinnon, Susan E

2013-05-03

256

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats.  

Science.gov (United States)

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/?l) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only-filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein-positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum-only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects. PMID:23746104

Berrocal, Yerko A; Almeida, Vania W; Gupta, Ranjan; Levi, Allan D

2013-06-07

257

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

UK PubMed Central (United Kingdom)

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

Saneinejad S; Shoichet MS

2000-06-01

258

Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme  

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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 activit...

Hemmert, Andrew C.; Otto, Tamara C.; Chica, Roberto A.; Wierdl, Monika; Edwards, Jonathan S.; Lewis, Steven L.

259

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(P)H 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; Dvoriantchikova Galina; Barakat David; Ivanov Dmitry; Bethea John R; Shestopalov Valery I

2012-01-01

260

Painful nerve injury decreases sarco-endoplasmic reticulum Ca²?-ATPase activity in axotomized sensory neurons.  

UK PubMed Central (United Kingdom)

The sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a critical pathway by which sensory neurons sequester cytosolic Ca(2+) and thereby maintain intracellular Ca(2+) homeostasis. We have previously demonstrated decreased intraluminal endoplasmic reticulum Ca(2+) concentration in traumatized sensory neurons. Here we examine SERCA function in dissociated sensory neurons using Fura-2 fluorometry. Blocking SERCA with thapsigargin (1 ?M) increased resting [Ca(2+)](c) and prolonged recovery (?) from transients induced by neuronal activation (elevated bath K(+)), demonstrating SERCA contributes to control of resting [Ca(2+)](c) and recovery from transient [Ca(2+)](c) elevation. To evaluate SERCA in isolation, plasma membrane Ca(2+) ATPase was blocked with pH 8.8 bath solution and mitochondrial buffering was avoided by keeping transients small (? 400 nM). Neurons axotomized by spinal nerve ligation (SNL) showed a slowed rate of transient recovery compared to control neurons, representing diminished SERCA function, whereas neighboring non-axotomized neurons from SNL animals were unaffected. Injury did not affect SERCA function in large neurons. Repeated depolarization prolonged transient recovery, showing that neuronal activation inhibits SERCA function. These findings suggest that injury-induced loss of SERCA function in small sensory neurons may contribute to the generation of pain following peripheral nerve injury.

Duncan C; Mueller S; Simon E; Renger JJ; Uebele VN; Hogan QH; Wu HE

2013-02-01

 
 
 
 
261

The effect of FES of the tibial nerve on physiological activation of leg muscles during gait.  

Science.gov (United States)

The effects of surface functional electrical stimulation (FES) of the tibial nerve of healthy subjects were evaluated. The FES was applied at three different times during gait: early, mid and late stances. The purpose of this work is to understand the effect of unilateral stimulation on the bilateral activation patterns of leg muscles, because FES is used in practice to improve gait, while associated neuromuscular change is not often measured. The experimental protocol presented here will be transferred to stroke subjects, who could benefit from improved push-off during gait. Results show that FES of the tibial nerve changes the offset timing of the tibialis anterior muscle on the stimulated side and the on- and offset timings of the tibialis anterior muscle of the leg contralateral to stimulation. Additionally, activity levels of the semitendinosus ipsilateral and tibialis anterior contralateral to the stimulated leg significantly decreased, with respect to the non-stimulated condition. For the semitendinosus, this was a difference of 6-7microV, with p<0.05. For the tibialis anterior, this was a difference of 7-15microV, with a significance of p=0.00, respectively. This information is important for future applications of stimulation as it means that stimulation not only affects the stimulated muscle but also the physiological motor control by the CNS. PMID:20138561

Monaghan, Colleen C; Hermens, Hermie J; Nene, Anand V; Tenniglo, Martin J B; Veltink, Peter H

2010-02-06

262

The effect of FES of the tibial nerve on physiological activation of leg muscles during gait.  

UK PubMed Central (United Kingdom)

The effects of surface functional electrical stimulation (FES) of the tibial nerve of healthy subjects were evaluated. The FES was applied at three different times during gait: early, mid and late stances. The purpose of this work is to understand the effect of unilateral stimulation on the bilateral activation patterns of leg muscles, because FES is used in practice to improve gait, while associated neuromuscular change is not often measured. The experimental protocol presented here will be transferred to stroke subjects, who could benefit from improved push-off during gait. Results show that FES of the tibial nerve changes the offset timing of the tibialis anterior muscle on the stimulated side and the on- and offset timings of the tibialis anterior muscle of the leg contralateral to stimulation. Additionally, activity levels of the semitendinosus ipsilateral and tibialis anterior contralateral to the stimulated leg significantly decreased, with respect to the non-stimulated condition. For the semitendinosus, this was a difference of 6-7microV, with p<0.05. For the tibialis anterior, this was a difference of 7-15microV, with a significance of p=0.00, respectively. This information is important for future applications of stimulation as it means that stimulation not only affects the stimulated muscle but also the physiological motor control by the CNS.

Monaghan CC; Hermens HJ; Nene AV; Tenniglo MJ; Veltink PH

2010-05-01

263

Central command does not decrease cardiac parasympathetic efferent nerve activity during spontaneous fictive motor activity in decerebrate cats.  

UK PubMed Central (United Kingdom)

To examine whether withdrawal of cardiac vagal efferent nerve activity (CVNA) predominantly controls the tachycardia at the start of exercise, the responses of CVNA and cardiac sympathetic efferent nerve activity (CSNA) were directly assessed during fictive motor activity that occurred spontaneously in unanesthetized, decerebrate cats. CSNA abruptly increased by 71 ± 12% at the onset of the motor activity, preceding the tachycardia response. The increase in CSNA lasted for 4-5 s and returned to the baseline, even though the motor activity was not ended. The increase of 6 ± 1 beats/min in heart rate appeared with the same time course of the increase in CSNA. In contrast, CVNA never decreased but increased throughout the motor activity, in parallel with a rise in mean arterial blood pressure (MAP). The peak increase in CVNA was 37 ± 9% at 5 s after the motor onset. The rise in MAP gradually developed to 21 ± 2 mmHg and was sustained throughout the spontaneous motor activity. Partial sinoaortic denervation (SAD) blunted the baroreflex sensitivity of the MAP-CSNA and MAP-CVNA relationship to 22-33% of the control. Although partial SAD blunted the initial increase in CSNA to 53% of the control, the increase in CSNA was sustained throughout the motor activity. In contrast, partial SAD almost abolished the increase in CVNA during the motor activity, despite the augmented elevation of 31 ± 1 mmHg in MAP. Because afferent inputs from both muscle receptors and arterial baroreceptors were absent or greatly attenuated in the partial SAD condition, only central command was operating during spontaneous fictive motor activity in decerebrate cats. Therefore, it is likely that central command causes activation of cardiac sympathetic outflow but does not produce withdrawal of cardiac parasympathetic outflow during spontaneous motor activity.

Kadowaki A; Matsukawa K; Wakasugi R; Nakamoto T; Liang N

2011-04-01

264

[Diffuse large B-cell lymphoma presenting with hypoglossal nerve palsy and great occipital neuralgia].  

UK PubMed Central (United Kingdom)

A 74-year-old man was hospitalized with hypoglossal nerve paralysis and severe great occipital neuralgia. Enhanced MRI of the head showed tumor on the left petrous bone, which compressed the medulla oblongata. Soluble IL-2 receptor was elevated and malignant lymphoma was clinically diagnosed. PET-CT demonstrated a single hot spot on the spleen. After radiation therapy to the lesion on the petrous bone, splenectomy was performed. Pathological findings established a diagnosis of diffuse large B-cell lymphoma. After chemotherapy consisting of rituximab and THP-COP, complete remission was achieved.

Kanai Y; Matsuda M; Iwanaga T; Hashimoto S; Maeda Y; Kanamaru A; Itagaki N

2009-02-01

265

Nerve growth factor receptor TrkA is expressed by horizontal and amacrine cells during chicken retinal development.  

UK PubMed Central (United Kingdom)

Nerve growth factor is known to stimulate neurite outgrowth and support neuronal survival during embryonic development. We have studied the expression of the nerve growth factor receptor, TrkA, at both mRNA and protein levels during the course of chicken retinal development. Furthermore, we have compared the expression of trkA mRNA with that of the 75-kD low-affinity neurotrophin receptor (p75NTR). RNase protection assay identified peak-levels of trkA mRNA in the late embryonic retina. Using in situ hybridization and immunohistochemistry, we found cells expressing TrkA in both the internal and the external part of the inner nuclear layer, corresponding to amacrine and horizontal cells, respectively. The TrkA-expressing amacrine cell has a unistratified dendritic arborization in the second sublamina of the inner plexiform layer, and may represent the stellate amacrine cell described by Cajal. The horizontal cells, possessing arciform dendrite processes in the outer plexiform layer, showed strong TrkA immunoreactivity in both dendrites and cell bodies. During the course of retinal development, the TrkA-expressing amacrine cells decreased in number, whereas the TrkA-expressing horizontal cells persisted. Because nerve growth factor was expressed where the horizontal cells, but not where the amacrine cells were located, these findings raise the question of whether nerve growth factor could locally support the survival of TrkA-expressing interneurons during retinal development.

Karlsson M; Clary DO; Lefcort FB; Reichardt LF; Karten HJ; Hallböök F

1998-10-01

266

Nerve growth factor receptor TrkA is expressed by horizontal and amacrine cells during chicken retinal development.  

Science.gov (United States)

Nerve growth factor is known to stimulate neurite outgrowth and support neuronal survival during embryonic development. We have studied the expression of the nerve growth factor receptor, TrkA, at both mRNA and protein levels during the course of chicken retinal development. Furthermore, we have compared the expression of trkA mRNA with that of the 75-kD low-affinity neurotrophin receptor (p75NTR). RNase protection assay identified peak-levels of trkA mRNA in the late embryonic retina. Using in situ hybridization and immunohistochemistry, we found cells expressing TrkA in both the internal and the external part of the inner nuclear layer, corresponding to amacrine and horizontal cells, respectively. The TrkA-expressing amacrine cell has a unistratified dendritic arborization in the second sublamina of the inner plexiform layer, and may represent the stellate amacrine cell described by Cajal. The horizontal cells, possessing arciform dendrite processes in the outer plexiform layer, showed strong TrkA immunoreactivity in both dendrites and cell bodies. During the course of retinal development, the TrkA-expressing amacrine cells decreased in number, whereas the TrkA-expressing horizontal cells persisted. Because nerve growth factor was expressed where the horizontal cells, but not where the amacrine cells were located, these findings raise the question of whether nerve growth factor could locally support the survival of TrkA-expressing interneurons during retinal development. PMID:9779944

Karlsson, M; Clary, D O; Lefcort, F B; Reichardt, L F; Karten, H J; Hallböök, F

1998-10-26

267

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

International Nuclear Information System (INIS)

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

2008-09-01

268

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

269

Urokinase plasminogen receptor and the fibrinolytic complex play a role in nerve repair after nerve crush in mice, and in human neuropathies.  

UK PubMed Central (United Kingdom)

Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies.

Rivellini C; Dina G; Porrello E; Cerri F; Scarlato M; Domi T; Ungaro D; Del Carro U; Bolino A; Quattrini A; Comi G; Previtali SC

2012-01-01

270

Guggulipid of Commiphora mukul, with antiallodynic and antihyperalgesic activities in both sciatic nerve and spinal nerve ligation models of neuropathic pain.  

Science.gov (United States)

Abstract Context: Guggulipid is a neutral fraction of ethyl acetate extract of gum resin of the tree Commiphora mukul Engl. (Burseraceae) and used in Ayurvedic medicine for treatment of neurological disorders. Objectives: The present study was undertaken to assess the antiallodynic and antihyperalgesic activities of guggulipid in rats. Materials and methods: The screening study included the CCI and L5-L6 SNL models of neuropathic pain. Guggulipid (100 and 50?mg/kg) or saline was administered intraperitoneally in a blinded, randomized manner from postoperative day (POD) 7 to 13. Paw withdrawal duration (PWD) to spontaneous pain, chemical allodynia and mechanical hyperalgesia and paw withdrawal latency (PWL) to mechanical allodynia and thermal hyperalgesia were tested before surgery, before and after guggulipid or saline administration (from POD7 to 13) and after the withdrawal of treatment (from POD14 to 20). Results: The activity profiles of the different doses of guggulipid were found to vary with time. In CCI rats, guggulipid (100 and 50?mg/kg) significantly (p?LD50 of guggulipid was 1600?mg/kg. In SNL rats, both doses of guggulipid were found to be ineffective in reversing the spontaneous pain but showing antiallodynic and antihyperalgesic activity. Discussion and conclusion: The results demonstrated that guggulipid produce antinociception in the peripheral nerve injury (CCI and SNL) models of neuropathic pain. The underlying mechanisms are expected to be modulating microglial activation occurring due to peripheral nerve injury. PMID:23862659

Goyal, Sachin; Khilnani, Gurudas; Singhvi, Indrajeet; Singla, Shivali; Khilnani, Ajeet K

2013-07-18

271

Comparison of the effects of cumene hydroperoxide and hydrogen peroxide on Retzius nerve cells of the leech Haemopis sanguisuga.  

UK PubMed Central (United Kingdom)

Oxidative stress and the production of reactive oxygen species are known to play a major role in neuronal cell damage, but the exact mechanisms responsible for neuronal injury and death remain uncertain. In the present study, we examined the effects of oxidative stress on spontaneous spike activity and depolarizing outward potassium current by exposing the Retzius neurons of the leech to cumene hydroperoxide (CHP) and hydrogen peroxide (H(2)O(2)), the oxidants commonly used to examine oxidative mechanisms mediating cell death. We observed that relatively low concentrations of CHP (0.25, 1, and 1.5 mM) led to a marked prolongation of spontaneous repetitive activity. The prolonged action potentials showed an initial, spike-like depolarization followed by a plateau phase. In contrast, H(2)O(2) at the same and much higher concentrations (0.25 to 5 mM) did not significantly change the duration of spontaneous spike potentials of leech Retzius nerve cells (LRNCs). In the voltage clamp experiments, calcium-activated outward potassium currents, needed for the repolarization of the action potential, were suppressed with CHP, but not with H(2)O(2). The present findings indicate that CHP is a more potent oxidant and neurotoxin than H(2)O(2) and that the effect of CHP on the electrophysiological properties of LRNCs may be due to the inhibition of the potassium channels.

Jovanovic Z; Jovanovic S

2013-01-01

272

Comparison of the effects of cumene hydroperoxide and hydrogen peroxide on Retzius nerve cells of the leech Haemopis sanguisuga.  

Science.gov (United States)

Oxidative stress and the production of reactive oxygen species are known to play a major role in neuronal cell damage, but the exact mechanisms responsible for neuronal injury and death remain uncertain. In the present study, we examined the effects of oxidative stress on spontaneous spike activity and depolarizing outward potassium current by exposing the Retzius neurons of the leech to cumene hydroperoxide (CHP) and hydrogen peroxide (H(2)O(2)), the oxidants commonly used to examine oxidative mechanisms mediating cell death. We observed that relatively low concentrations of CHP (0.25, 1, and 1.5 mM) led to a marked prolongation of spontaneous repetitive activity. The prolonged action potentials showed an initial, spike-like depolarization followed by a plateau phase. In contrast, H(2)O(2) at the same and much higher concentrations (0.25 to 5 mM) did not significantly change the duration of spontaneous spike potentials of leech Retzius nerve cells (LRNCs). In the voltage clamp experiments, calcium-activated outward potassium currents, needed for the repolarization of the action potential, were suppressed with CHP, but not with H(2)O(2). The present findings indicate that CHP is a more potent oxidant and neurotoxin than H(2)O(2) and that the effect of CHP on the electrophysiological properties of LRNCs may be due to the inhibition of the potassium channels. PMID:23357941

Jovanovic, Zorica; Jovanovic, Svetlana

2013-01-01

273

Nerve growth factor receptor TrkA exists as a preformed, yet inactive, dimer in living cells.  

UK PubMed Central (United Kingdom)

The tropomyosin-related kinase A (TrkA) receptor and its ligand, nerve growth factor (NGF), play crucial roles in the development and function of the nervous system. NGF is believed to activate TrkA by bridging two TrkA monomers, leading to TrkA transphosphorylation. However, here we show that the majority of TrkA receptors exist as preformed, yet inactive, homodimers prior to NGF binding by using three different approaches such as chemical crosslinking and enzyme fragment complementation assay. Furthermore, TrkA homodimers are formed in endoplasmic reticulum before newly synthesized receptors reach the cell surface. These findings shed light on molecular mechanisms underlying transmembrane signaling by TrkA.

Shen J; Maruyama IN

2011-01-01

274

Distal segment extracts of the degenerated rat sciatic nerve induce bone marrow stromal cells to express Schwann cell markers in vitro.  

UK PubMed Central (United Kingdom)

Bone marrow stromal cells (MSCs) have the ability to support nerve regeneration when transplanted into lesion sites, but the mechanism is unclear. We hypothesized that specific factors in the lesioned microenvironment induce the differentiation of transplanted MSCs into functional Schwann-like cells. To test this hypothesis and determine the origin of such factors, we investigated the effects of different extracts from degenerated rat sciatic nerves on MSCs in vitro. After 3 days of degeneration, extracts from the distal segment (Ds) and proximal segment (Ps) of the rat sciatic nerve were used in experiments. After 1 day of treatment, the morphology of MSCs cultured with Ds extracts were spindle shaped, and the cells interconnected with each other, followed by gradual loss of typical morphology during culture. After 7 days of treatment, western blotting and RT-PCR analyses indicated that the cells cultured with Ds extracts had significantly higher expression of glial fibrillary acidic protein (GFAP), Sox10, Oct6, and early growth response 2(Egr2) than that of cells cultured with Ps extracts and the untreated cells. Our study suggests that, in the microenvironments of nerve lesions, specific factors induce MSCs to differentiate into functional Schwann-like cells, which may originate from the Ds of the degenerated nerve. These results may help to elucidate the mechanisms by which MSCs function in peripheral nerve repair.

Wang H; Zhang H; Liu M; Wang N

2013-06-01

275

Distal segment extracts of the degenerated rat sciatic nerve induce bone marrow stromal cells to express Schwann cell markers in vitro.  

Science.gov (United States)

Bone marrow stromal cells (MSCs) have the ability to support nerve regeneration when transplanted into lesion sites, but the mechanism is unclear. We hypothesized that specific factors in the lesioned microenvironment induce the differentiation of transplanted MSCs into functional Schwann-like cells. To test this hypothesis and determine the origin of such factors, we investigated the effects of different extracts from degenerated rat sciatic nerves on MSCs in vitro. After 3 days of degeneration, extracts from the distal segment (Ds) and proximal segment (Ps) of the rat sciatic nerve were used in experiments. After 1 day of treatment, the morphology of MSCs cultured with Ds extracts were spindle shaped, and the cells interconnected with each other, followed by gradual loss of typical morphology during culture. After 7 days of treatment, western blotting and RT-PCR analyses indicated that the cells cultured with Ds extracts had significantly higher expression of glial fibrillary acidic protein (GFAP), Sox10, Oct6, and early growth response 2(Egr2) than that of cells cultured with Ps extracts and the untreated cells. Our study suggests that, in the microenvironments of nerve lesions, specific factors induce MSCs to differentiate into functional Schwann-like cells, which may originate from the Ds of the degenerated nerve. These results may help to elucidate the mechanisms by which MSCs function in peripheral nerve repair. PMID:23583596

Wang, Hui; Zhang, Hongyu; Liu, Mo; Wang, Ningyu

2013-04-09

276

Inhibition effect of the deltamethrin and phoxim mixtures on the sodium channels of nerve cell  

UK PubMed Central (United Kingdom)

The results showed that these mixtures were more powerful inhibitors of sodium currents than single pesticides, more rapidly reducing the action potential and blocking the nerve impulse of axon membrane. Recording of whole cell sodium currents showed that slow decaying tail currents were associated with repolarization following a depolarizing pulse in deltamethrin modified cells. The average constant of tail currents was concentration independent. Most cells showed a marked reduction in peak current with only a few showing an increase. The inhibition of sodium channels was concentration-dependent and could not recover later. We concluded that deltamethrin modified the action kinetics of sodium channels in such a way as to slow opening, prolong closure or otherwise inactivate them and that this modification occurs predominantly when the channels are in the closed or resting state. The inhibition of sodium currents will cause the reduction of action potential and loss of electrical excitability of axon membrane.

Gao Yongchuang; Guo Zhenqun; Liu Anxi; Han Jiaxiang

2002-01-01

277

Use of phenoxyacetic acid derivatives for obtaining a medicament intended for restoring function to nerve cells  

UK PubMed Central (United Kingdom)

The invention relates to the field of human or animal therapy. It relates more especially to the field of therapeutic chemistry, and is directed especially towards pharmaceutical compositions containing as active principle at least one p-chlorophenoxyacetate of general formula I R1 is hydrogen, a monovalent cation derived from an inorganic or organic base or from an amino acid or alternatively an optionally substituted lower alkyl radical, in combination or mixed with a pharmaceutically acceptable, non-toxic, inert excipient. The pharmaceutical compositions according to the invention serve to restore function to nerve fibres after lesion or trauma or in cases of degeneration.

278

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.

Eglen Stephen J; Lofgreen Dan D; Raven Mary A; Reese Benjamin E

2008-01-01

279

Nerve Growth Factor Prevents Demyelination, Cell Death and Progression of the Disease in Experimental Allergic Encephalomyelitis  

Directory of Open Access Journals (Sweden)

Full Text Available Experimental allergic encephalomyelitis (EAE), a demyelinating disease induced in the animals parallels multiple sclerosis in human in several aspects, provides a useful model to investigate multiple sclerosis. In this study, we have therefore used this model to study functions of nerve growth factor (NGF) in EAE. NGF with considerable effects on neuron survival, proliferation and differentiation of the nervous system, is also known to act on cells of the immune system. Simultaneous upregulation of proinflammatory cytokines and increased level of NGF points at possible effects of the nerve growth factor in autoimmune diseases. To investigate roles of NGF in experimental allergic encephalomyelitis in vivo, we therefore decided to apply it intracerebroventricularly at a dose of 0.20 mg/mice prior to the induction of EAE. Our clinical observations showed that in the EAE induced animals who received NGF, severity of the disease was reduced significantly compared to that in saline treated EAE mice. Also neuropathological investigation of spinal cords revealed that in contrast to saline treated EAE mice, no signs of cell death, infiltration and demyelination can be seen in NGF treated EAE mice, suggesting that NGF may have clinical implications in multiple sclerosis.

Azita Parvaneh Tafreshi

2006-01-01

280

Inverted colloidal crystal scaffolds with induced pluripotent stem cells for nerve tissue engineering.  

UK PubMed Central (United Kingdom)

The development of biomaterials for regenerating neurons from induced pluripotent stem (iPS) cells is crucial to the potential therapy for traumatic injury to nervous system. This study aims to guide differentiation of iPS cells into neuron-lineage cells in inverted colloidal crystal (ICC) scaffolds containing alginate, poly(?-glutamic acid), and surface CSRARKQAASIKVAVSADR (peptide). The differentiation of iPS cells in ICC constructs was characterized by staining of embryonic and neuronal markers. The results indicated that hexagonal crystals of polystyrene microspheres shaped hydrogels into ICC scaffolds with interconnected pores. CSRARKQAASIKVAVSADR slightly enhanced the adhesion of iPS cells in ICC constructs and yielded no variation in the viability of iPS cells. Cultured ICC constructs with CSRARKQAASIKVAVSADR reduced the expression of stage-specific embryonic surface antigen-1 and raised the expression of ? III tubulin of differentiating iPS cells. The induction with CSRARKQAASIKVAVSADR in ICC topography can improve the differentiation of iPS cells toward neurons for nerve tissue engineering.

Kuo YC; Chen CW

2013-02-01

 
 
 
 
281

Transcorneal electrical stimulation alters morphology and survival of retinal ganglion cells after optic nerve damage.  

Science.gov (United States)

Traumatic optic nerve injury leads to retrograde death of retinal ganglion cells (RGCs), but transcorneal electrical stimulation (TES) can increase the cell survival rate. To understand the mechanisms and to further define the TES-induced effects we monitored in living animals RGC morphology and survival after optic nerve crush (ONC) in real time by using in vivo confocal neuroimaging (ICON) of the retina. ONC was performed in rats and ICON was performed before crush and on post-lesion days 3, 7 and 15 which allowed us to repeatedly record RGC number and size. TES or sham-stimulation were performed immediately after the crush and on post-injury day 11. Three days after ONC we detected a higher percentage of surviving RGCs in the TES group as compared to sham-treated controls. However, the difference was below significance level on day 7 and disappeared completely by day 15. The death rate was more variable amongst the TES-treated rats than in the control group. Morphological analysis revealed that average cell size changed significantly in the control group but not in stimulated animals and the morphological alterations of surviving neurons were smaller in TES-treated compared to control cells. In conclusion, TES delays post-traumatic cell death significantly. Moreover, we found "responder animals" which also benefited in the long-term from the treatment. Our in vivo cellular imaging results provide evidence that TES reduces ONC-associated neuronal swelling and shrinkage especially in RGCs which survived long-term. Further studies are now needed to determine the differences of responders vs. non-responders. PMID:23523651

Henrich-Noack, Petra; Voigt, Nadine; Prilloff, Sylvia; Fedorov, Anton; Sabel, Bernhard A

2013-03-21

282

Transcorneal electrical stimulation alters morphology and survival of retinal ganglion cells after optic nerve damage.  

UK PubMed Central (United Kingdom)

Traumatic optic nerve injury leads to retrograde death of retinal ganglion cells (RGCs), but transcorneal electrical stimulation (TES) can increase the cell survival rate. To understand the mechanisms and to further define the TES-induced effects we monitored in living animals RGC morphology and survival after optic nerve crush (ONC) in real time by using in vivo confocal neuroimaging (ICON) of the retina. ONC was performed in rats and ICON was performed before crush and on post-lesion days 3, 7 and 15 which allowed us to repeatedly record RGC number and size. TES or sham-stimulation were performed immediately after the crush and on post-injury day 11. Three days after ONC we detected a higher percentage of surviving RGCs in the TES group as compared to sham-treated controls. However, the difference was below significance level on day 7 and disappeared completely by day 15. The death rate was more variable amongst the TES-treated rats than in the control group. Morphological analysis revealed that average cell size changed significantly in the control group but not in stimulated animals and the morphological alterations of surviving neurons were smaller in TES-treated compared to control cells. In conclusion, TES delays post-traumatic cell death significantly. Moreover, we found "responder animals" which also benefited in the long-term from the treatment. Our in vivo cellular imaging results provide evidence that TES reduces ONC-associated neuronal swelling and shrinkage especially in RGCs which survived long-term. Further studies are now needed to determine the differences of responders vs. non-responders.

Henrich-Noack P; Voigt N; Prilloff S; Fedorov A; Sabel BA

2013-05-01

283

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

UK PubMed Central (United Kingdom)

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.

Kunz D; Walker G; Bedoucha M; Certa U; März-Weiss P; Dimitriades-Schmutz B; Otten U

2009-01-01

284

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.

Kunz Dieter; Walker Gaby; Bedoucha Marc; Certa Ulrich; März-Weiss Pia; Dimitriades-Schmutz Beatrice; Otten Uwe

2009-01-01

285

Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat.  

Science.gov (United States)

The respiratory system expresses multiple forms of plasticity, defined as alterations in the breathing pattern that persist or develop after a stimulus. Stimulation of breathing with intermittent hypoxia (IH) elicits long-term facilitation (LTF), a type of plasticity in which respiratory motor activity progressively increases in anaesthetized animals, even after the stimuli have ceased and blood gases have normalized. It is unknown whether the sympathetic nervous system similarly expresses IH-induced plasticity, but we predicted that IH would evoke LTF in sympathetic nerve activity (SNA) because respiratory and sympathetic control systems are coupled. To test this idea, we recorded splanchnic (sSNA) and phrenic nerve activities (PNA) in equithesin-anaesthetized rats. Animals were exposed to 10 45 s episodes of 8% O(2)-92% N(2), separated by 5 min intervals of 100% O(2), and recordings were continued for 60 min following the last hypoxic exposure. Cycle-triggered averages of integrated PNA and sSNA from periods preceding, and 5 and 60 min following the hypoxic stimuli were compared. Intermittent hypoxia significantly increased both sSNA and PNA. Treatment with methysergide (3 mg kg(-1), i.v.) 20 min before the intermittent hypoxic exposures prevented the increases in integrated PNA and sSNA 60 min after IH, indicating a role of serotonergic pathways in this form of plasticity. No increases in PNA and sSNA occurred at comparable times (60 and 120 min) in rats not exposed to hypoxia. The increased sSNA was not simply tonic, but was correlated with respiratory bursts, and occurred predominantly during the first half of expiration. These findings support the hypothesis that sympathorespiratory coupling may underlie the sustained increase in SNA associated with the IH that occurs during sleep apnoea. PMID:17138622

Dick, Thomas E; Hsieh, Yee-Hsee; Wang, Ning; Prabhakar, Nanduri

2006-11-30

286

Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat.  

UK PubMed Central (United Kingdom)

The respiratory system expresses multiple forms of plasticity, defined as alterations in the breathing pattern that persist or develop after a stimulus. Stimulation of breathing with intermittent hypoxia (IH) elicits long-term facilitation (LTF), a type of plasticity in which respiratory motor activity progressively increases in anaesthetized animals, even after the stimuli have ceased and blood gases have normalized. It is unknown whether the sympathetic nervous system similarly expresses IH-induced plasticity, but we predicted that IH would evoke LTF in sympathetic nerve activity (SNA) because respiratory and sympathetic control systems are coupled. To test this idea, we recorded splanchnic (sSNA) and phrenic nerve activities (PNA) in equithesin-anaesthetized rats. Animals were exposed to 10 45 s episodes of 8% O(2)-92% N(2), separated by 5 min intervals of 100% O(2), and recordings were continued for 60 min following the last hypoxic exposure. Cycle-triggered averages of integrated PNA and sSNA from periods preceding, and 5 and 60 min following the hypoxic stimuli were compared. Intermittent hypoxia significantly increased both sSNA and PNA. Treatment with methysergide (3 mg kg(-1), i.v.) 20 min before the intermittent hypoxic exposures prevented the increases in integrated PNA and sSNA 60 min after IH, indicating a role of serotonergic pathways in this form of plasticity. No increases in PNA and sSNA occurred at comparable times (60 and 120 min) in rats not exposed to hypoxia. The increased sSNA was not simply tonic, but was correlated with respiratory bursts, and occurred predominantly during the first half of expiration. These findings support the hypothesis that sympathorespiratory coupling may underlie the sustained increase in SNA associated with the IH that occurs during sleep apnoea.

Dick TE; Hsieh YH; Wang N; Prabhakar N

2007-01-01

287

Evaluation of electrical activity after vagus nerve-preserving distal gastrectomy using multichannel electrogastrography.  

UK PubMed Central (United Kingdom)

Background: Multichannel electrogastrography (M-EGG) can be used to evaluate gastrointestinal motility. The myoelectric activity of the remnant stomach after surgery has not been measured by M-EGG. This study examined whether myoelectric activity varied with surgical technique and compared vagus nerve-preserving distal gastrectomy (VP-DG) with standard distal gastrectomy without vagus nerve preservation (DG). Furthermore, we examined the relationship between the M-EGG findings and patients' postoperative symptoms.Methods: Twenty-six patients who underwent VP-DG, 20 who underwent DG, and 12 healthy volunteers as controls were examined with M-EGG. The Gastrointestinal Symptom Rating Scale (GSRS) was used to assess postoperative symptoms.Results: Longer periods of normal gastric function (normogastria, 2.0-4.0 cycle min(-1)) were detected in channel 1 in the VP-DG group than in the DG group in either the fasted or fed state (P<0.05). The percentage of slow wave coupling (%SWC) in the fed state correlated negatively with GSRS scores (reflux, r=-0.59, P=0.02; abdominal pain, r=-0.51, P=0.04, indigestion, r=-0.59, P=0.02 and total score, r=-0.75, P=0.02).Conclusions: Slow waves can be recorded non-invasively using M-EGG in the remnant stomach following gastrectomy. The VP-DG group showed better preserved gastric myoelectric activity than the DG group, and the %SWC showed a significant negative correlation with scores of GSRS (reflux, abdominal pain, indigestion and total score) in the VP-DG group.

Murakami H; Matsumoto H; Kubota H; Higashida M; Nakamura M; Hirai T

2013-01-01

288

Facial nerve repair with Gore-Tex tube and adipose-derived stem cells: an animal study in dogs.  

UK PubMed Central (United Kingdom)

PURPOSE: Synthetic conduits have been considered a viable option in nerve reconstructive procedures. They address the goal of entubulization and eliminate the disadvantages of autografts. However, despite all successful reports, none has contained regeneration characteristics, such as growth factors or essential cells, for nerve repair. The authors evaluated the capability of adipose-derived stem cells in Gore-Tex tubes to enhance facial nerve repair. MATERIALS AND METHODS: Undifferentiated mesenchymal stem cells were extracted from the autogenous adipose tissues of 7 mongrel dogs. The frontal branch of the facial nerve was transected. A gap size of 7 mm was repaired with an expanded polytetrafluoroethylene tube filled with undifferentiated adipose-derived stem cells encapsulated in alginate hydrogel. The control sides were repaired with the tube and alginate alone. The healing phase was 12 weeks. RESULTS: Except in 2 control sides, an organized neural tissue was formed within the tubes. Compared with the normal nerve diameter, there was a decreased ratio of 29% and 39% in the experimental and control groups, respectively. Neurofilament-positive axon counts were 67% of normal values in the 2 groups. There was no significant difference between groups in histomorphometric parameters. Nerve conduction velocity in the experimental group (28.5 ± 3.5 m/s) was significantly greater than in the control group (16.2 ± 7 m/s). The experimental group also exhibited a greater maximal amplitude of action potential (1.86 ± 0.24 mV) than the control group (1.45 ± 0.49 mV). CONCLUSIONS: Addition of stem cells in the Gore-Tex tube enhanced the neural repair from a functional standpoint. However, for better functional and histologic results, differentiated Schwann cells and other mediators may be warranted.

Ghoreishian M; Rezaei M; Beni BH; Javanmard SH; Attar BM; Zalzali H

2013-03-01

289

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

290

Influence of genioglossus tonic activity on upper airway dynamics assessed by phrenic nerve stimulation.  

UK PubMed Central (United Kingdom)

Upper airway (UA) dynamics can be evaluated during wakefulness by using electrical phrenic nerve stimulation (EPNS) applied at end-expiration during exclusive nasal breathing by dissociating twitch flow and phasic activation of UA muscles. This technique can be used to quantify the influence of nonphasic electromyographic (EMG) activity on UA dynamics. UA dynamics was characterized by using EPNS when increasing tonic EMG activity with CO(2) stimulation in six normal awake subjects. Instantaneous flow, esophageal and nasopharyngeal pressures, and genioglossal EMG activity were recorded during EPNS at baseline and during CO(2) ventilatory stimulation. The proportion of twitches presenting an inspiratory-flow limitation pattern decreased from 100% at baseline to 78.7 +/- 21.4% (P = 10(-4)) during CO(2) rebreathing. During CO(2) stimuli, maximal inspiratory twitch flow (VI(max)) of flow-limited twitches significantly rose, with the driving pressure at which flow limitation occurred being more negative. For the group as a whole, the increase in VI(max) and the decrease in pressure were significantly correlated with the rise in end-expiratory EMG activity. UA stability assessed by EPNS is dramatically modified during CO(2) ventilatory stimulation. Changes in tonic genioglossus EMG activity significantly contribute to the improvement in UA stability.

Sériès F; Marc I

2002-01-01

291

Influence of genioglossus tonic activity on upper airway dynamics assessed by phrenic nerve stimulation.  

Science.gov (United States)

Upper airway (UA) dynamics can be evaluated during wakefulness by using electrical phrenic nerve stimulation (EPNS) applied at end-expiration during exclusive nasal breathing by dissociating twitch flow and phasic activation of UA muscles. This technique can be used to quantify the influence of nonphasic electromyographic (EMG) activity on UA dynamics. UA dynamics was characterized by using EPNS when increasing tonic EMG activity with CO(2) stimulation in six normal awake subjects. Instantaneous flow, esophageal and nasopharyngeal pressures, and genioglossal EMG activity were recorded during EPNS at baseline and during CO(2) ventilatory stimulation. The proportion of twitches presenting an inspiratory-flow limitation pattern decreased from 100% at baseline to 78.7 +/- 21.4% (P = 10(-4)) during CO(2) rebreathing. During CO(2) stimuli, maximal inspiratory twitch flow (VI(max)) of flow-limited twitches significantly rose, with the driving pressure at which flow limitation occurred being more negative. For the group as a whole, the increase in VI(max) and the decrease in pressure were significantly correlated with the rise in end-expiratory EMG activity. UA stability assessed by EPNS is dramatically modified during CO(2) ventilatory stimulation. Changes in tonic genioglossus EMG activity significantly contribute to the improvement in UA stability. PMID:11744686

Sériès, F; Marc, I

2002-01-01

292

Negative regulators of schwann cell differentiation-novel targets for peripheral nerve therapies?  

UK PubMed Central (United Kingdom)

As myelinating glial cells of the peripheral nervous system, Schwann cells wrap around axons and thereby provide insulation, acceleration of electric signal propagation, and axonal protection and maintenance. Schwann cells are main effectors for regeneration in a variety of peripheral neuropathic conditions, including inherited, inflammatory, toxic, and diabetic neuropathies, as well as traumatic injuries to peripheral nerve fibers. Due to their high differentiation plasticity, these cells can respond to injury and disease by myelin sheath degradation, dedifferentiation into an immature Schwann cell-like phenotype, proliferation, and remyelination of sprouting axons. In doing so, they can support and promote axonal regrowth and target tissue innervation. Developmental differentiation as well as regenerative de- and redifferentiation are tightly controlled by a balance of positive and negative regulators of Schwann cell maturation. Since misregulated expression of such negative regulators is potentially involved in inefficient or failed regeneration, we will provide an overview about recent work revealing the complex interactions between extrinsic and intrinsic signals in the inhibition of Schwann cell differentiation.

Heinen A; Lehmann HC; Küry P

2013-01-01

293

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

Science.gov (United States)

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

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

2013-04-01

294

The use of Cytodex 3 microcarriers and reduced-serum media for the production of nerve growth promoters from chicken heart cells.  

UK PubMed Central (United Kingdom)

Microcarrier cell culture provides an efficient method for the production of cell products. Cytodex 3 microcarriers were used for the production of an active nerve growth-promoting substance from chicken heart fibroblasts (1 degree -4 degrees cultures). Such cells release into culture medium a factor which stimulates the growth of nerve fibres from explanted ciliary, sympathetic and spinal neurons. Furthermore, culture in low-serum or serum-free media reduces the presence of contaminating proteins and facilitates the production and biochemical analysis of this factor. A mixture of DME/F 10 was supplemented with either 10% (v/v) foetal calf serum (FCS), 0.5% FCS, a low molecular weight fraction of FCS, (MW less than 10,000; prepared by dialysis) or different hormones and growth factors. Cells cultured in medium supplemented with insulin (I, 1 microgram/ml), transferrin (T, 25 micrograms/ml), human serum albumin (HSA, 2 mg/ml) and fibronectin (F, 10 micrograms/ml) (ITAF) in combination with 0.5% FCS or a low molecular weight fraction of FCS progressed through the cell cycle with normal kinetics and maximum DNA synthesis was after 20 h. The results were similar to those obtained with a supplement of 10% FCS alone. Media supplemented with insulin, transferrin, fibronectin and HSA in combination with dexamethasone (200 ng/ml) or epidermal growth factor (10 ng/ml) did not promote cell proliferation to the same extent. The fibroblasts proliferated on Cytodex 3 at a rate similar to cells grown on cell culture plastic and produced sufficient amounts of nerve growth-promoting substance for biological analysis. Production of this factor was generally associated with cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Norrgren G; Ebendal T; Gebb C; Wikström D

1983-01-01

295

Reserve activated electrochemical cell  

Energy Technology Data Exchange (ETDEWEB)

This paper describes a reserve activated electrochemical cell. It comprises: a cell reactive fluid storage tubular spiral, an electrochemical cell plate container means for storing cell plates and located within the turns of the tubular spiral and adjacent to a first end of the tubular spiral, a rupturable means for providing a fluid-tight separation of the spiral and the container means and an intermediate spacer means for selectively attaching the first end to the container means while providing a fluid channel including the rupturable means.

Kulkarni, M.V.

1991-11-26

296

Long-range correlation of renal sympathetic nerve activity in both conscious and anesthetized rats.  

Science.gov (United States)

In this study we employed both detrended fluctuation analysis (DFA) and multiscale entropy (MSE) measurements to compare the long-range temporal correlation (LRTC) of multifibre renal sympathetic nerve activity (RSNA) between conscious and anesthetized Wistar rats. It was found that both methods showed the obvious LRTC properties in conscious state. Moreover, the scaling exponent of the RSNA in conscious rats was significantly higher than that in anesthetized rats. The results of MSE analysis showed that the entropy values, derived from the conscious group, increased on small time scales and then stabilized to a relatively constant value whereas the entropy measure, derived from anesthetized animals, almost monotonically decreased. This suggests that the fractal properties of underlying dynamics of the system have been reduced by anesthesia. The results demonstrate that apparently random fluctuations in multifibre RSNA are dictated by a complex deterministic process that imparts "long-term" memory to the dynamic system. However, this memory is significantly weakened by anesthesia. PMID:18511128

Li, Yatang; Qiu, Jiaheng; Yang, Zhuo; Johns, Edward J; Zhang, Tao

2008-04-25

297

[Effect of ethacizin (diethylamine analog of ethmozine) on the efferent activity of the sympathetic and parasympathetic nerves of the heart  

UK PubMed Central (United Kingdom)

This study examined the effects of the diethylamino analogue of ethmozin (ethacizin) (1 mg/kg, i.v.) on the spontaneous and reflex elicited efferent activity in thoracic cardiac sympathetic and parasympathetic nerves. Nitroglycerin and phenylephrine (4 and 8 micrograms/kg, i.v.) were administered to 15 anesthetized mongrel dogs while monitoring blood pressure and heart rate. In each dog, two cardiac nerves were isolated and efferent neurograms were simultaneously recorded and analyzed by microprocessor. Ethacizin significantly attenuated the spontaneous sympathetic efferent activity in both left and right, preganglionic (n-8) and postganglionic (n-14) sympathetic nerves to the heart. In contrast, reflex changes in sympathetic activity elicited by baroreceptor challenges, were not affected by ethacizin. Also, ethacizin did not significantly affect either spontaneous or baroreceptor reflex-induced parasympathetic efferent activities in 8 preganglionic nerves. Thus, this new phenothiazine derivative may exert part of its antiarrhythmic action through a reduction of the spontaneous sympathetic tonic discharges to the heart. The fact that ethacizin did neither reduce the reflex-induced changes in sympathetic or parasympathetic activities nor influence the tonic vagal discharges further suggests that the compound is not likely to interfere with reflexly mediated cardiovascular adaptive changes.

Khageman GR; Nili BKh; Urtaler F; Rozenshtraukh LV

1986-04-01

298

Respiratory influences on muscle sympathetic nerve activity and vascular conductance in the steady state.  

UK PubMed Central (United Kingdom)

In patients with hypertension, volitional slowing of the respiratory rate has been purported to reduce arterial pressure via withdrawal of sympathetic tone. We examined the effects of paced breathing at 7, 14, and 21 breaths/min, with reciprocal changes in tidal volume, on muscle sympathetic nerve activity, forearm blood flow, forearm vascular conductance, and blood pressure in 21 men and women, 8 of whom had modest elevations in systemic arterial pressure. These alterations in breathing frequency and volume did not affect steady-state levels of sympathetic activity, blood flow, vascular conductance, or blood pressure (all P > 0.05), even though they had the expected effect on sympathetic activity within breaths (i.e., increased modulation during low-frequency/high-tidal volume breathing) (P < 0.001). These findings were consistent across subjects with widely varied baseline levels of sympathetic activity (4-fold), mean arterial pressure (78-110 mmHg), and vascular conductance (15-fold), and those who became hypocapnic during paced breathing vs. those who maintained normocapnia. These findings challenge the notion that slow, deep breathing lowers arterial pressure by suppressing steady-state sympathetic outflow.

Limberg JK; Morgan BJ; Schrage WG; Dempsey JA

2013-06-01

299

Slit-Robo GTPase-activating proteins are differentially expressed in murine dorsal root ganglia: modulation by peripheral nerve injury.  

UK PubMed Central (United Kingdom)

The Slit-Robo GTPase-activating proteins (srGAPs) play an important role in neurite outgrowth and axon guidance; however, little is known about its role in nerve regeneration after injury. Here, we studied the expression of srGAPs in mouse dorsal root ganglia (DRG) following sciatic nerve transection (SNT) using morphometric and immunohistochemical techniques. Reverse transcriptase polymerase chain reaction and Western blot analysis indicated that srGAP1 and srGAP3, but not srGAP2, were expressed in normal adult DRG. Following unilateral SNT, elevated mRNA and protein levels of srGAP1 and srGAP3 were detected in the ipsilateral relative to contralateral L(3-4) DRGs from day 3 to day 14. Immunohistochemical results showed that srGAP1 and srGAP3 were largely expressed in subpopulations of DRG neurons in naïve DRGs. However, after SNT, srGAP3 in neurons was significantly increased in the ipsilateral relative to contralateral DRGs, which peaked at day 7 to day 14. Interestingly, DRG neurons with strong srGAP3 labeling also coexpressed Robo2 after peripheral nerve injury. These results suggest that srGAPs are differentially expressed in murine DRG and srGAP3 are the predominant form. Moreover, srGAP3 may participate in Slit-Robo signaling in response to peripheral nerve injury or the course of nerve regeneration.

Chen ZB; Zhang HY; Zhao JH; Zhao W; Zhao D; Zheng LF; Zhang XF; Liao XP; Yi XN

2012-04-01

300

Slit-Robo GTPase-activating proteins are differentially expressed in murine dorsal root ganglia: modulation by peripheral nerve injury.  

Science.gov (United States)

The Slit-Robo GTPase-activating proteins (srGAPs) play an important role in neurite outgrowth and axon guidance; however, little is known about its role in nerve regeneration after injury. Here, we studied the expression of srGAPs in mouse dorsal root ganglia (DRG) following sciatic nerve transection (SNT) using morphometric and immunohistochemical techniques. Reverse transcriptase polymerase chain reaction and Western blot analysis indicated that srGAP1 and srGAP3, but not srGAP2, were expressed in normal adult DRG. Following unilateral SNT, elevated mRNA and protein levels of srGAP1 and srGAP3 were detected in the ipsilateral relative to contralateral L(3-4) DRGs from day 3 to day 14. Immunohistochemical results showed that srGAP1 and srGAP3 were largely expressed in subpopulations of DRG neurons in naïve DRGs. However, after SNT, srGAP3 in neurons was significantly increased in the ipsilateral relative to contralateral DRGs, which peaked at day 7 to day 14. Interestingly, DRG neurons with strong srGAP3 labeling also coexpressed Robo2 after peripheral nerve injury. These results suggest that srGAPs are differentially expressed in murine DRG and srGAP3 are the predominant form. Moreover, srGAP3 may participate in Slit-Robo signaling in response to peripheral nerve injury or the course of nerve regeneration. PMID:22271578

Chen, Zhi-Bing; Zhang, Hai-Ying; Zhao, Jiu-Hong; Zhao, Wei; Zhao, Dan; Zheng, Lin-Feng; Zhang, Xian-Fang; Liao, Xiao-Ping; Yi, Xi-Nan

2012-01-24

 
 
 
 
301

Sympathetic nerve activity can be estimated from skin conductance responses - A comment on Henderson et al. (2012).  

UK PubMed Central (United Kingdom)

A recent paper by Henderson et al. (2012) claimed that skin sympathetic nerve activity (SSNA) can not be retrieved from skin conductance responses (SCR). Here, I argue that this claim is not supported by the literature, and comment on contemporary approaches of estimating SSNA from SCR using biophysical models.

Bach DR

2013-08-01

302

Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity (MSNA). Animal studies support the concept that low-frequency electroacupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, m...

Stener-Victorin, E; Jedel, E; Janson, PO; Sverrisdottir, YB

303

[Expressions of P-JNK in nerve cell apoptosis of A2AR knockout newborn mice after hypoxia/ischemia brain damage].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To investigate the effect of adenosine A2A receptor knockout (A(2A)RKO) on relationship between continuous activation of phospho-c-Jun N-terminal kinase (P-JNK) and expression of nerve cell apoptosis in hippocampus CA1 domain of newborn mice after hypoxia/ischemia brain damage(HIBD) and its potential mechanism. METHODS: A(2A)RKO mice and adenosine A2A receptor wildtype (A(2A)RWT) littermates (n = 80) were divided into Sham operation group (S) and model group (M), 1, 3 and 7 day after HIBD, totally 8 groups. HIBD was developed with 7 day-old neonatal mice according classical Rice-Vannucci method. It was tested the effect of A(2A)RKO on short-term neurofunctional outcomes consisted of three developmental reflexes (righting, geotaxis and cliff aversion), the changes of brain pathology with hematoxylin-eosin (HE) staining and Nissl staining, the expressions of nerve cell apoptosis with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling(TUNEL) staining and P-JNK were observed by immunohistochemistry. RESULTS: The neurological behavior injuries and brain histopathological damages and nerve apoptosis cells were aggravated in A(2A)RKO newborn mice after HIBD. The positive expressions of P-JNK were significantly higher in the ischemic hippocampus CA1 domain after HIBD than ones in group S respectively (P < 0.01), reaching to peak at 1 day and then began gradually decreasing. P-JNK expression in model knockout(MKO) at 1, 3 and 7 day increased greatly compared to those in the previous time point of corresponding model wildtype (MWT) (P < 0.01, P < 0.05, P > 0.05); there was a positive correlation between the expressions of P-JNK and nerve cell apoptosis after HIBD in newborn mice(r = 0.837, P < 0.01). CONCLUSION: Early continuous activation of P-JNK might be involved in the aggravated nerve apoptosis cells and brain damage induced by A(2A) RKO newborn mice after HIBD.

Fan HL; Yin SG; Lou P; Ren SW; Huang S; Chen X

2013-03-01

304

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

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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 rat...

Unsicker, K; Vey, J; Hofmann, H D; Müller, T H; Wilson, A J

305

Challenges for stem cells to functionally repair the damaged auditory nerve.  

UK PubMed Central (United Kingdom)

INTRODUCTION: In the auditory system, a specialized subset of sensory neurons are responsible for correctly relaying precise pitch and temporal cues to the brain. In individuals with severe-to-profound sensorineural hearing impairment these sensory auditory neurons can be directly stimulated by a cochlear implant, which restores sound input to the brainstem after the loss of hair cells. This neural prosthesis therefore depends on a residual population of functional neurons in order to function effectively. AREAS COVERED: In severe cases of sensorineural hearing loss where the numbers of auditory neurons are significantly depleted, the benefits derived from a cochlear implant may be minimal. One way in which to restore function to the auditory nerve is to replace these lost neurons using differentiated stem cells, thus re-establishing the neural circuit required for cochlear implant function. Such a therapy relies on producing an appropriate population of electrophysiologically functional neurons from stem cells, and on these cells integrating and reconnecting in an appropriate manner in the deaf cochlea. EXPERT OPINION: Here we review progress in the field to date, including some of the key functional features that stem cell-derived neurons would need to possess and how these might be enhanced using electrical stimulation from a cochlear implant.

Needham K; Minter RL; Shepherd RK; Nayagam BA

2013-01-01

306

Nerve growth induces 5-HT sub 3 recognition sites in rat pheochromocytoma (PC12) cells  

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

Gordon, J.C.; Rowland, H.C. (A.H. Robins Research Laboratories, Richmond, VA (USA))

1990-01-01

307

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

International Nuclear Information System (INIS)

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

1990-01-01

308

DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2.  

Science.gov (United States)

To elucidate the role of epigenetic reprogramming in cell- or tissue-specific differentiation, we explored the role of DNA methyltransferases (Dnmts) in the nerve growth factor (NGF)-induced differentiation of PC12 (pheochromocytoma) cells into neuronal cells. The mRNA and protein levels of de novo methyltransferase Dnmt3b increased, whereas those of Dnmt3a and Dnmt1 decreased, during NGF-induced neurite outgrowth. Dnmt3b localized in the nucleus, as well as in the growing neurites. When the expression of Dnmt3b was inhibited by antisense or small interfering RNA, PC12 cells continued to proliferate and failed to generate neurites. Cells depleted of Dnmt3b were unable to exit the cell cycle even after 6 days of NGF treatment. Furthermore, this failure in differentiation correlated with significant attenuation in tyrosine phosphorylation of TrkA (a marker for NGF-induced differentiation) and reduced the expression of neuronal markers, Hu antigen, and MAP2. The methyl-CpG content of the PC12 genome or the methylation status of repetitive elements was not significantly altered after differentiation and was not affected by Dnmt3b depletion. This was consistent with the ability of the catalytic-site mutant of Dnmt3b to induce differentiation in Dnmt3b-depleted cells after NGF treatment. The Dnmt3b-mediated differentiation was attributed to its N-terminal domain, which recruits histone deacetylase 2 (Hdac2), as demonstrated by (i) impeding of differentiation by the Hdac inhibitors, (ii) facilitation of the differentiation process by overexpression of the N-terminal domain of Dnmt3b, (iii) higher Hdac activity associated with Dnmt3b after NGF treatment, and (iv) coimmunoprecipitation and cosedimentation of Dnmt3b specifically with Hdac2 in a glycerol density gradient. These data indicate a novel role of Dnmt3b in neuronal differentiation. PMID:15632075

Bai, Shoumei; Ghoshal, Kalpana; Datta, Jharna; Majumder, Sarmila; Yoon, Sung Ok; Jacob, Samson T

2005-01-01

309

[Quantitative determination of the disintegration of nerve cells in the cortex caused by viral encephalitis (17 D-yellow fever), as a basis for the evaluation of the pathological processes in the central nerve system (author's transl)  

UK PubMed Central (United Kingdom)

A loss of nerve cells in the cortex after encephalitis was reported already in the classical work by Nissl, Spielmeyer, and Spatz. A loss of nerve cells will become only noticeable if it amounts to at least 50%. But as such clear pictures are rarely found, estimations were always considered as doubtful and incorrect. Not only the number of cells is important in consideration of the morphological change in the cortex but also the size of cells. The development of a new apparatus made is possible to consider two structural parameters: the surface and the perimeter of cells. In 497 histological serial preparations obtained from 43 mouse brains we determined the number, the surface, and the perimeter of nerve cells. 39 animals were infected intracerebraly with yellow fever 17 D; 4 normal animals served as controls. Among the infected animals, 8 were treated with a mucopolysaccharide. The cells were counted within a determined area (standard unity); this area was taken from the angle between the curbura exterior and the sulcus anterior-posterior of the brain. There was a significant difference between the number of nerve cells in normal (278) and in infected (202) animals. The animals treated with mucopolysaccharide showed a normal quantity of nerve cells but surface and perimeter corresponded to the data of the infected ones. The surface of normal animals was at 23.39, that of infected at 14.29. There was also a significant difference with regard to the cell perimeter: normal 14.97, infected 12.02. This means a shrinking of cells. The cell shrinkage revealed that the nerve cells were affected. The measurement of these three parameters presents new and exact statistical findings which enable a reconsideration of neurovirulence.

Museteanu C; Haase J; Stiens R; Henneberg G

1980-01-01

310

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 < 0.005) in the EA group. No correlation was found for BMI and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine and metabolic variables. Conclusions: For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for women with PCOS.

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

311

Carbachol stimulates a different phospholipid metabolism than nerve growth factor and basic fibroblast growth factor in PC12 cells.  

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We have examined 1,2-diglycerides (DGs) generated in PC12 cells in response to the muscarinic agonist carbachol and compared them with those generated in response to the differentiation factors nerve growth factor and basic fibroblast growth factor. Whereas carbachol stimulates a greater release of ...

Pessin, M S; Altin, J G; Jarpe, M; Tansley, F; Bradshaw, R A; Raben, D M

312

[Optic nerve schwannoma].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To report the occurrence of an orbital schwannoma probably arising from the optic nerve sheath. PATIENT AND METHOD: Clinical case report. RESULTS: A 65-year-old patient presented with a painless, progressive right proptosis over five years. Magnetic resonance imaging revealed an intraconal mass, radiographically consistent with a cavernous hemangioma. Surgical resection was performed and pathology disclosed a schwannoma affecting the optic nerve. The optic nerve, which does not contain Schwann cells, is exceptionally rarely affected by Schwannomas, which may arise from a few sympathetic nerve fibers or from a few ectopic cells, not normally present within the optic nerve. CONCLUSION: The radiologic appearance of the very rare optic nerve Schwannoma may be confused with a cavernous hemangioma, a more common tumor in this location.

Leruez S; Gohier P; Menei P; Milea D

2013-03-01

313

[Histological picture of altered nerve cells of the sympathetic trunk of healthy and mature nutria (Myocastor coupus Mol.)  

UK PubMed Central (United Kingdom)

Histological investigations were carried out on the sympathetic trunks of fourteen healthy, mature male and female coypu specimens of standard race, aged 8-24 months. The histological preparations impregnated using Bielschowski and Gross's method were prepared from front cervical, mid-cervical (central cervical), and pectoral-cervical ganglia as well as from pectoral, lumbar and sacral ganglia. An entire range of nerve cells displaying a certain type and degree of change was found in the above mentioned sympathetic ganglia. These cells are classified in the following order: cells with protoplasmic argyrophilia, cells with vacuole formations, with hyperplasia or hypertrophia of the processes, neuronophagic cells and degenerating cells.

Langenfeld M

1981-01-01

314

Neuropeptide RFRP inhibits the pacemaker activity of terminal nerve GnRH neurons.  

UK PubMed Central (United Kingdom)

The terminal nerve gonadotropin-releasing hormone (TN-GnRH) neurons show spontaneous pacemaker activity whose firing frequency is suggested to regulate the release of GnRH peptides and control motivation for reproductive behaviors. Previous studies of the electrophysiological properties of TN-GnRH neurons reported excitatory modulation of pacemaker activity by auto/paracrine and synaptic modulations, but inhibition of pacemaker activity has not been reported to date. Our recent study suggests that neuropeptide FF, a type of Arg-Phe-amide (RFamide) peptide expressed in TN-GnRH neurons themselves, inhibits the pacemaker activity of TN-GnRH neurons in an auto- and paracrine manner. In the present study, we examined whether RFamide-related peptides (RFRPs), which are produced in the hypothalamus, modulate the pacemaker activity of TN-GnRH neurons as candidate inhibitory synaptic modulators. Bath application of RFRP2, among the three teleost RFRPs, decreased the frequency of firing of TN-GnRH neurons. This inhibition was diminished by RF9, a potent antagonist of GPR147/74, which are candidate RFRP receptors. RFRP2 changed the conductances for Na(+) and K(+). The reversal potential for RFRP2-induced current was altered by inhibitors of the transient receptor potential canonical (TRPC) channel (La(3+) and 2-aminoethoxydiphenyl borate) and by a less selective blocker of voltage-independent K(+) channels (Ba(2+)). By comparing the current-voltage relationship in artificial cerebrospinal fluid with that under each drug, the RFRP2-induced current was suggested to consist of TRPC channel-like current and voltage-independent K(+) current. Therefore, synaptic release of RFRP2 from hypothalamic neurons is suggested to inhibit the pacemaker activity of TN-GnRH neurons by closing TRPC channels and opening voltage-independent K(+) channels. This novel pathway may negatively regulate reproductive behaviors.

Umatani C; Abe H; Oka Y

2013-05-01

315

Skeletal muscle reflex-mediated changes in sympathetic nerve activity are abnormal in spontaneously hypertensive rats.  

UK PubMed Central (United Kingdom)

In hypertension, the blood pressure response to exercise is exaggerated. We demonstrated previously that this heightened pressor response to physical activity is mediated by an overactive skeletal muscle exercise pressor reflex (EPR), with important contributions from its metaboreflex and mechanoreflex components. However, the mechanisms driving the abnormal blood pressure response to EPR activation are largely unknown. Recent evidence in humans suggests that the muscle metaboreflex partially mediates the enhanced EPR-induced pressor response via abnormally large changes in sympathetic nerve activity (SNA). Whether the muscle mechanoreflex induces similarly exaggerated alterations in SNA in hypertension remains unknown, as does the role of the mechanoreceptors mediating muscle reflex activity. To address these issues, the EPR was selectively activated by electrically inducing hindlimb muscle contraction in decerebrate normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Stimulation of the EPR evoked significantly larger increases in mean arterial pressure (MAP) and renal SNA (RSNA) in SHR compared with WKY (?RSNA from baseline: 140 ± 11 vs. 48 ± 8%). The mechanoreflex was stimulated by stretching hindlimb muscle which likewise elicited significantly greater elevations in MAP and RSNA in SHR than WKY (?RSNA from baseline: 105 ± 11 vs. 35 ± 7%). Blockade of mechanoreceptors in muscle with gadolinium significantly attenuated the MAP and RSNA responses to contraction and stretch in SHR. These data suggest that 1) the exaggerated pressor response to activation of the EPR and muscle mechanoreflex in hypertension is mediated by abnormally large reflex-induced augmentations in SNA and 2) this accentuated sympathetic responsiveness is evoked, in part, by stimulation of muscle mechanoreceptors.

Mizuno M; Murphy MN; Mitchell JH; Smith SA

2011-03-01

316

Diagnostic ability of retinal ganglion cell complex, retinal nerve fiber layer, and optic nerve head measurements by Fourier-domain optical coherence tomography.  

UK PubMed Central (United Kingdom)

PURPOSE: To evaluate the diagnostic ability of Fourier-domain optical coherence tomography (FD-OCT) measurements in glaucoma patients, patients with ocular hypertension, and normal subjects. METHODS: Ninety-three participants with open-angle glaucoma (OAG), 58 patients with ocular hypertension (OHT), and 60 healthy control subjects were included in the study. All study participants underwent FD-OCT imaging. Retinal ganglion cell complex (GCC), macular thickness, peripapillary retinal nerve fiber layer thickness (RFNL), and optic nerve head parameters (ONH) were measured in each participant. The diagnostic ability was evaluated using area under the receiver operating characteristics curves (AUROC). RESULTS: Glaucoma patients showed a significant reduction in GCC and macular retinal thickness compared to patients with OHT and normal subjects. No differences in GCC were found between the patients with OHT and normal subjects. The best diagnostic ability in the comparison between glaucoma and normal subjects after adjusting for age was found for cup-to-disc ratio (AUROC?=?0.848), RNFL average thickness (AUROC?=?0.828), and GCC global loss volume (AUROC?=?0.805). The diagnostic power of the best GCC, RNFL, and ONH parameter did not show differences beyond random variation (p?>?0.05). CONCLUSIONS: Imaging of the GCC using FD-OCT (RTVue-100) has a comparable diagnostic ability to RNFL and ONH measurements in distinguishing between glaucoma patients and healthy subjects. No differences were found between patients with OHT and normal subjects with regard to ONH, RNFL, and GCC parameters.

Schulze A; Lamparter J; Pfeiffer N; Berisha F; Schmidtmann I; Hoffmann EM

2011-07-01

317

Patterns of lipofuscin accumulation in ganglionic nerve cells of superior cervical ganglion in humans  

Directory of Open Access Journals (Sweden)

Full Text Available Background/Aim. Considering available literature lipofuscin is a classical age pigment of postmitotic cells, and a consistently recognized phenomenon in humans and animals. Lipofuscin accumulation is characteristic for nerve cells that are postmitotic. This research was focused on lipofuscin accumulation in ganglionic cells (GC) (postganglionic sympathetic cell bodies) of superior cervical ganglion in humans during ageing. Methods. We analysed 30 ganglions from cadavers ranging from 20 to over 80 years of age. As material the tissue samples were used from the middle portion of the ganglion, which was separated from the surrounding tissue by the method of macrodissection. The tissue samples were routinely fixed in 10% neutral formalin and embedded in paraffin for classical histological analysis, then three consecutive (successive) sections 5 ?m thick were made and stained with hematoxylin and eosin method (HE), silver impregnation technique by Masson Fontana and trichrome stain by Florantin. Results. Immersion microscopy was used to analyse patterns of lipofuscin accumulation during ageing making possible to distinguish diffuse type (lipofuscin granules were irregularly distributed and non-confluent), unipolar type (lipofuscin granules were grouped at the end of the cell), bipolar type (lipofuscin granules were concentrated at the two opposite ends of a cell with the nucleus in between at the center of a cell), annular type (lipofuscin granules were in the shape of a complete or incomplete ring around the nucleus) and a cell completely filled with lipofuscin (two subtypes distinguishing, one with visible a nucleus, and the other with invisible one). Even at the age of 20 there were cells with lipofuscin granules accumulated in diffuse way, but in smaller numbers; the GC without lipofuscin were dominant. Growing older, especially above 60 years, all of the above mentioned patterns of lipofuscin accumulation were present with the evident increase in cells completely filled with lipofuscin, but cells without lipofuscin were also present even in the oldest persons. Conclusion. Lipofuscin is present in all periods of ageing with a different intensity of accumulation. GC without the pigment, diffusely distributed, as well as very rare cells with a unipolar type of lipofuscin distribution are characteristic for the age of 20- 60 years. In the age above 60 years, except the cells without pigment and diffuse accumulation type, there are also bipolar and annular types and forms in which cells are completely filled with lipofuscin granules.

Živkovi? Vladimir; Stefanovi? Natalija; ?urovi?-Filipovi? Tatjana; Pavlovi? Snežana; Stojanovi? Vesna; Baki? Mirjana; Kundali? Braca; Pavlovi? Miljana

2008-01-01

318

Nerve growth factor regulates galanin and c-jun overexpression occurring in dorsal root ganglion cells after intravesical resiniferatoxin application.  

UK PubMed Central (United Kingdom)

Galanin and c-jun expression after a single bladder instillation of resiniferatoxin was studied by immunocytochemistry in L6 dorsal root ganglia (DRG) neurons of the rat. The role of nerve growth factor depletion in causing that effect was also investigated. Three days after instillation of a 100 nM resiniferatoxin solution a marked increase in the number of galanin and c-Jun immunoreactive DRG cells was evident bilaterally. The increments were still present at 8 days and disappeared 1 month after treatment. Systemic administration of nerve growth factor, 100 microg/kg, prevented both overexpressions. Results suggest that the changes induced in bladder sensory neurons by intravesical resiniferatoxin are due, at least in part, to the temporary deprivation of bladder-derived neurotrophic factors, namely nerve growth factor, in those neurons.

Avelino A; Cruz C; Cruz F

2002-10-01

319

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

UK PubMed Central (United Kingdom)

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. GLIA 2013.

Dey I; Midha N; Singh G; Forsyth A; Walsh SK; Singh B; Kumar R; Toth C; Midha R

2013-10-01

320

The role of C-terminal binding protein 2 in Schwann cell differentiation after sciatic nerve crush.  

UK PubMed Central (United Kingdom)

C-terminal binding protein 2 (CtBP2), as a transcriptional repressor, plays an essential role in development and tumorigenesis. However, its distribution and function in peripheral system lesion and repair are still unknown. Here, we investigated the spatiotemporal expression of CtBP2 in rat sciatic nerve crush model. Western blot analysis revealed that CtBP2 was expressed in normal sciatic nerve. It gradually decreased, reached minimal levels at 7 days after crush, and then returned to the normal level at 4 weeks. We observed that CtBP2 is mainly expressed in Schwann cells (SCs). In vitro, we induced SC differentiation via cyclic adenosine monophosphate (cAMP) and found that CtBP2 expression was downregulated during the process of differentiation. CtBP2-specific siRNA inhibited the cAMP-induced expression of the immature SC marker P75(NTR), and exogenous CtBP2 expression upregulated the expression of P75(NTR). Taken together, we hypothesized that peripheral nerve crush-induced downregulation of CtBP2 in the sciatic nerve was associated with SC differentiation, and CtBP2 likely played an important role in peripheral nerve injury and regeneration.

Cao X; Zhao P; Tao G; Zhu Y; Zhou F; Cui Z; Bao G; Xu D; Zhang G; Chen X

2013-03-01

 
 
 
 
321

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

UK PubMed Central (United Kingdom)

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 (2mM) which did not change the amplitude of PBC significantly decreased peak afferent firing from 79 ± 15 spikes/s to 44 ± 8 spikes/s in CYP pretreated but not untreated preparations. In CYP treated preparations SNAP also decreased by 33-55% BAN firing induced by isotonic distension of the bladder at 10-40 cmH(2)O pressures. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. SNAP significantly increased the voltage threshold by 75% (p<0.05) and decreased by 45% (p<0.05) the area of the AP evoked at submaximal stimulus intensity. Bath application of SNAP (2mM) or l-arginine (50mM) elicited similar inhibitory effects on the distension evoked BAN firing. The effects of l-arginine were blocked by bath application of l-NAME (20mM). l-NAME alone did not alter BAN firing. In preparations from normal rats SNAP or l-arginine did not alter BAN activity. These results suggest that exogenous as well as endogenously generated NO depresses the excitability of sensitized but not normal BAN and that NO may have an antinociceptive function and modulate bladder hyperactivity induced by pathological conditions.

Yu Y; de Groat WC

2013-01-01

322

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

Directory of Open Access Journals (Sweden)

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

Saito Harukazu; Dahlin Lars B

2008-01-01

323

Spinal neuroimmune activation inhibited by repeated administration of pioglitazone in rats after L5 spinal nerve transection.  

UK PubMed Central (United Kingdom)

Neuroimmune activation contributes to the generation and maintenance of neuropathic pain after peripheral nerve injury. Peroxisome proliferator activated receptor gamma (PPAR-?) agonists have potential neuroprotection. The current study aimed to determine the effects of a PPAR-? agonist pioglitazone on mechanical hyperalgesia and neuroimmune activation in a rat model of neuropathic pain induced by L5 spinal nerve transection (SNT). Thirty-two rats were equally randomized into 4 groups: sham operation with vehicle; L5 SNT with vehicle or pioglitazone; or L5 SNT with pioglitazone and a PPAR-? antagonist GW9662. Pioglitazone or vehicle was administered 1h before operation and continued daily to day 14 after operation. The paw pressure threshold (PPT) was measured before operation and on days 3, 7, 14 after operation. Glial fibrillary acidic protein (GFAP) expression, tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6 levels, and nuclear factor-kappa B (NF-?B) activity in the lumbar spinal cord were determined on day 14 after operation. The results displayed pioglitazone improved the mechanical hyperalgesia, and attenuated the astrocyte and NF-?B activation and the inflammatory cytokine upregulation in nerve-injured rats, which might be reversed by GW9662. In conclusion, pioglitazone ameliorates the mechanical hyperalgesia induced by L5 SNT via inhibiting the spinal neuroimmune activation in rats, suggesting spinal PPAR-? signaling pathway may be involved in the pathogenesis of mechanical hyperalgesia.

Jia HB; Wang XM; Qiu LL; Liu XY; Shen JC; Ji Q; Yang JJ

2013-05-01

324

[The hyperinnervation phenomenon and the gradient distribution of nerve-growth-factor activity in the tissue of the regenerating rat liver  

UK PubMed Central (United Kingdom)

An increase in the number and fluorescence intensity of liver nerve structures was recorded using fluorescent-histochemical method following 50% resection of the left lobe of the liver. Simultaneous isolation of liver NGF showed its activity in the operated lobe to have had gradient distribution, which motivated successful growth of nerve fibers to the zone of regeneration and development of hyperinnervation in it.

Isanbaev ChI

1995-01-01

325

Analgesic ineffectiveness of lacosamide after spinal nerve ligation and its sodium channel activity in injured neurons.  

UK PubMed Central (United Kingdom)

BACKGROUND: Lacosamide is a novel anti-epileptic drug that enhances the slow- and not fast-inactivating state of voltage-gated sodium channels. Lacosamide has demonstrated analgesic efficacy in several animal studies but preclinical studies on neuropathic pain models are rare, and recent clinical trials showed no superior analgesic effects. METHODS: Here, we examine whether an acute or chronic administration of lacosamide (3-60?mg/kg, i.p.) attenuates pain behaviour induced by spinal nerve ligation (SNL). To validate the inhibitory efficacy of lacosamide on voltage-gated sodium channels, sodium currents in naïve and SNL-injured dorsal root ganglion (DRG) neurons were recorded using whole-cell patch clamping. RESULTS: Lacosamide only marginally attenuated thermal hyperalgesia, but not tactile allodynia when applied once 7 or 14 days after SNL and showed no analgesic effect when applied daily for 19 days. In naïve neurons, 100??mol/L lacosamide inhibited sodium channel currents by 58% and enhanced the slow inactivation (87% for lacosamide vs. 47% for control). In contrast, lacosamide inhibited sodium currents in injured DRG neurons by only 15%, while the effects on slow inactivation were diminished. Isolated currents from the NaV 1.8 channel subtype were only marginally changed by lacosamide. CONCLUSION: The reduced effectiveness of lacosamide on voltage-gated sodium channel currents in injured DRG neurons may contribute to the reduced analgesic effect observed for the SNL model.

Hagenacker T; Schäfer N; Büsselberg D; Schäfers M

2013-07-01

326

Zhangfei induces the expression of the nerve growth factor receptor, trkA, in medulloblastoma cells and causes their differentiation or apoptosis.  

UK PubMed Central (United Kingdom)

Interactions between nerve growth factor (NGF) and its receptor-the tropomyosin related kinase A (trkA)-regulate many neuronal functions including the correct development of sensory neurons during embryogenesis, the survival of sensory neurons and the differentiation and apoptosis of neuronal tumours. Zhangfei is a transcriptional factor that is expressed in differentiated neurons. Since we could detect Zhangfei in mature neurons but not in neuronal tumour cells, we hypothesised that ectopic expression of the protein in medulloblastoma cells may induce the differentiation of these cells. We show that in ONS-76 medulloblastoma cells, resveratrol, an inducer of apoptosis and differentiation, increased the expression of Zhangfei, trkA and Early Growth Response Gene 1 (Egr1), a gene normally activated by NGF-trkA signalling. ONS-76 cells stopped growing soon after treatment with resveratrol. While the induction of Zhangfei in resveratrol-treated cells was modest albeit consistent, the infection of actively growing medulloblastoma cells with an adenovirus vector expressing Zhangfei mimicked some of the effects of resveratrol. Ectopically expressed Zhangfei in ONS-76 cells led to the increased expression of trkA and Egr1, phosphorylation of extracellular signal-regulated kinase (Erk1), and caused ONS-76 cells to display markers of apoptosis. UW228, another medulloblastoma cell-line, was also susceptible to the suppressive effects of resveratrol and Zhangfei. In contrast, while resveratrol suppressed the growth of human diploid fibroblasts (MRC5), Zhangfei had relatively little effect on these cells.

Valderrama X; Rapin N; Verge VM; Misra V

2009-01-01

327

In Vivo Characterization of Intracellular Signaling Pathways Activated by the Nerve Agent Sarin.  

Science.gov (United States)

Organophosphorous (OP) nerve agents, such as sarin, exert acute effects by inhibiting acetylcholinesterase in the central and peripheral nervous systems, which results in accumulation of acetylcholine and, in turn, an excessive stimulation of nicotinic an...

T. A. Shih G. L. Snyder J. P. Hendrick A. A. Fienberg J. H. McDonough

2004-01-01

328

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

2013-05-01

329

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

UK PubMed Central (United Kingdom)

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.

Su X; Nickles A; Nelson DE

2013-07-01

330

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.

Nickles, Angela; Nelson, Dwight E.

2013-01-01

331

Electroacupuncture changes the relationship between cardiac and renal sympathetic nerve activities in anesthetized cats.  

Science.gov (United States)

Electroacupuncture (EA) is known to affect hemodynamics through modulation of efferent sympathetic nerve activity (SNA), however, possible regional differences in the SNA response to EA remains to be examined. Based on the discordance between arterial blood pressure and heart rate changes during EA, we hypothesized that regional differences would occur among SNAs during EA. To test this hypothesis, we compared changes in cardiac and renal SNAs in response to 1-min EA (10 Hz or 2 Hz) of a hind limb in adult cats anesthetized with pentobarbital sodium. Renal SNA remained decreased for 1 min during EA (P<0.01 for both 10 Hz and 2 Hz). In contrast, cardiac SNA tented to decrease only in the beginning of EA. It increased during the end of EA (P<0.05 for 2 Hz) and further increased after the end of EA (P<0.01 both for 10 Hz and 2 Hz). There was a quasi-linear relationship between renal and cardiac SNAs with a slope of 0.69 (i.e., renal SNA was more suppressed than cardiac SNA) during the last 10 s of EA. The discrepancy between the renal and cardiac SNAs persisted after sinoaortic denervation and vagotomy. In conclusion, EA evokes differential patterns of SNA responses and changes the relationship between cardiac and renal SNAs. PMID:18990613

Yamamoto, Hiromi; Kawada, Toru; Kamiya, Atsunori; Kita, Toru; Sugimachi, Masaru

2008-11-05

332

Weakened long-range correlation of renal sympathetic nerve activity in Wistar rats after anaesthesia.  

Science.gov (United States)

In this study we employed multiscale entropy (MSE) measurement to assess the long-range temporal correlation (LRTC) of multifibre renal sympathetic nerve activity (RSNA) signals in conscious and anaesthetized Wistar rats. It was found that both groups presented more complex MSE profiles than an uncorrelated process. Moreover, the results of MSE analysis of RSNA demonstrated that the entropy values, derived from the conscious group, increased on small time scales and then stabilized to a relatively constant value, however, the entropy measure, derived from animals with anaesthesia, almost monotonically decreased. The present study shows that while LRTC in the temporal dynamics of energy fluctuations of RSNA does not implicate a unique mechanism, the data for the first time provide evidence of much less temporal correlation in anaesthetized condition. This suggests the fractal properties of underlying dynamical system have been effectively eliminated by anaesthesia. These results demonstrate that apparently random fluctuations in multifibre RSNA are dictated by a complex deterministic process that imparts "long-term" memory to the dynamic system. However, this memory is significantly weakened by anaesthesia. PMID:18206307

Li, Yatang; Qiu, Jiaheng; Yan, Rui; Yang, Zhuo; Zhang, Tao

2008-03-01

333

Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors.  

Science.gov (United States)

Vagus nerve stimulation (VNS) is an FDA approved treatment for drug-resistant epilepsy and depression. Recently, we demonstrated the capacity for repeatedly pairing sensory input with brief pulses of VNS to induce input specific reorganization in rat auditory cortex. This was subsequently used to reverse the pathological neural and perceptual correlates of hearing loss induced tinnitus. Despite its therapeutic potential, VNS mechanisms of action remain speculative. In this study, we report the acute effects of VNS on intra-cortical synchrony, excitability, and sensory processing in anesthetized rat auditory cortex. VNS significantly increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6-8 Hz but not after application of the muscarinic antagonist scopolamine. Collectively, these experiments demonstrate the capacity for VNS to acutely influence cortical synchrony and excitability and strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in VNS mechanisms of action. These results are discussed with respect to their possible implications for sensory processing, neural plasticity, and epilepsy. PMID:21627982

Nichols, J A; Nichols, A R; Smirnakis, S M; Engineer, N D; Kilgard, M P; Atzori, M

2011-05-26

334

Effects of intracavernous injection of adipose-derived stem cells on cavernous nerve regeneration in a rat model.  

UK PubMed Central (United Kingdom)

The aim of this study was to investigate effects of intracavernous injection of adipose-derived stem cells (ADSCs) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Thirty Sprague-Dawley male rats were randomly divided into three equal groups: one group underwent sham operation, while two groups underwent bilateral CN crush. Crush-injury group was treated at the time of injury with intracavernous injection of ADSCs, or injured control group with no further intervention. Erectile function was assessed by CN electrostimulation after 3 months. Penile tissue and crushed nerves were collected for histology. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate intracavernous injection of ADSCs, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the intracavernous injection of ADSCs had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibers than the injured control group but fewer than the sham group. Intracavernous injection of ADSCs treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. These results show that the intracavernous injection of ADSCs to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that penile injection of ADSCs can improve recovery of erectile function in a rat model of neurogenic ED.

Ying C; Yang M; Zheng X; Hu W; Wang X

2013-03-01

335

Effects of intracavernous injection of adipose-derived stem cells on cavernous nerve regeneration in a rat model.  

Science.gov (United States)

The aim of this study was to investigate effects of intracavernous injection of adipose-derived stem cells (ADSCs) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Thirty Sprague-Dawley male rats were randomly divided into three equal groups: one group underwent sham operation, while two groups underwent bilateral CN crush. Crush-injury group was treated at the time of injury with intracavernous injection of ADSCs, or injured control group with no further intervention. Erectile function was assessed by CN electrostimulation after 3 months. Penile tissue and crushed nerves were collected for histology. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate intracavernous injection of ADSCs, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the intracavernous injection of ADSCs had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibers than the injured control group but fewer than the sham group. Intracavernous injection of ADSCs treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. These results show that the intracavernous injection of ADSCs to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that penile injection of ADSCs can improve recovery of erectile function in a rat model of neurogenic ED. PMID:23161147

Ying, Chengcheng; Yang, Mei; Zheng, Xinmin; Hu, Wanli; Wang, Xinghuan

2012-11-17

336

Granular cell tumor in a lumbar spinal nerve of a dog.  

UK PubMed Central (United Kingdom)

A 2-year-old Great Dane dog with a 2.5-week history of progressive paraparesis was presented to the Veterinary Medical Teaching Hospital at the University of Wisconsin-Madison. Neurologic examination revealed nonambulatory paraparesis with reduced to absent withdrawal hind-limb reflexes and lumbar pain. Magnetic resonance imaging and gross pathology confirmed a larger regional lumbar mass and a second smaller extradural mass within the spinal canal. The left lumbar mass was associated with extensive hemorrhage; dissection showed a dark-red, soft, well-circumscribed mass measuring 2 cm x 1.5 cm x 0.5 cm within the left fourth lumbar spinal nerve. Histopathological evaluation with immunohistochemistry revealed sheets of round to polygonal cells with diffuse granular cytoplasm demonstrating diastase-resistant periodic acid-Schiff reactivity and positive immunoexpression of S100 and neuron-specific enolase. The smaller extradural mass within the spinal canal exhibited similar morphology. Based on gross, histological, and immunohistochemical evidence, the masses were diagnosed as granular cell tumor.

Rao D; Rylander H; Drees R; Schwarz T; Steinberg H

2010-07-01

337

Retinal nerve fiber layer and ganglion cell layer thickness in patients receiving systemic isotretinoin therapy.  

Science.gov (United States)

To evaluate the effect of oral isotretinoin therapy on retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness by spectral domain optical coherence tomography (OCT). This prospective study included newly diagnosed nodulocystic acne patients about to receive isotretinoin treatment. Macular average GCL thickness and peripapillary average, temporal, nasal, inferior, and superior quadrant RNFL thickness were measured by OCT before and after isotretinoin treatment. Pre- and post-treatment measurements were compared with paired t test. Fifty-six eyes of 28 patients were included. The mean duration of the treatment was 6.5 ± 1.3 months. The mean average GCL thickness was 90.04 ± 5.87 (80-96) ?m at baseline and 90.75 ± 6.34 (81-96) ?m after treatment. The mean average RNFL thickness was 93.25 ± 6.06 ?m (84-107) before treatment and 93.05 ± 5.54 ?m (82-106) after treatment. There were no statistically significant differences between pre- and post-treatment values (all p > 0.05). A 6-month course of systemic isotretinoin therapy seems to have no unfavorable effect on retinal ganglion cells; however, larger studies with longer follow-up periods are needed to be conclusive. PMID:23338233

Sekeryapan, Berrak; D?lek, Nursel; Oner, Veysi; Turky?lmaz, Kemal; Aslan, Mehmet Gokhan

2013-01-23

338

Retinal nerve fiber layer and ganglion cell layer thickness in patients receiving systemic isotretinoin therapy.  

UK PubMed Central (United Kingdom)

To evaluate the effect of oral isotretinoin therapy on retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness by spectral domain optical coherence tomography (OCT). This prospective study included newly diagnosed nodulocystic acne patients about to receive isotretinoin treatment. Macular average GCL thickness and peripapillary average, temporal, nasal, inferior, and superior quadrant RNFL thickness were measured by OCT before and after isotretinoin treatment. Pre- and post-treatment measurements were compared with paired t test. Fifty-six eyes of 28 patients were included. The mean duration of the treatment was 6.5 ± 1.3 months. The mean average GCL thickness was 90.04 ± 5.87 (80-96) ?m at baseline and 90.75 ± 6.34 (81-96) ?m after treatment. The mean average RNFL thickness was 93.25 ± 6.06 ?m (84-107) before treatment and 93.05 ± 5.54 ?m (82-106) after treatment. There were no statistically significant differences between pre- and post-treatment values (all p > 0.05). A 6-month course of systemic isotretinoin therapy seems to have no unfavorable effect on retinal ganglion cells; however, larger studies with longer follow-up periods are needed to be conclusive.

Sekeryapan B; D?lek N; Oner V; Turky?lmaz K; Aslan MG

2013-01-01

339

Regional correlation among ganglion cell complex, nerve fiber layer, and visual field loss in glaucoma.  

UK PubMed Central (United Kingdom)

PURPOSE: To analyze the relationship among macular ganglion cell complex (GCC) thickness, peripapillary nerve fiber layer (NFL) thickness, and visual field (VF) defects in patients with glaucoma. METHODS: A Fourier-domain optical coherence tomography (FD-OCT) system was used to map the macula and peripapillary regions of the retina in 56 eyes of 38 patients with perimetric glaucoma. The macular GCC and peripapillary NFL thicknesses were mapped and standard automated perimetry (SAP) was performed. Loss of GCC and NFL were correlated with the VF map on both a point-by-point and regional basis. RESULTS: Correlation between GCC thickness and peripapillary NFL thickness produced a detailed correspondence map that demonstrates the arcuate course of the NFL in the macula. Corresponding regions within the GCC, NFL, and VF maps demonstrate significant correlation, once parafoveal retinal ganglion cell (RGC) displacement is taken into account. CONCLUSIONS: There are significant point-specific and regional correlations between GCC loss, NFL loss, and deficits on SAP. Using these different data sources together may improve our understanding of glaucomatous damage and aid in the management of patients with glaucoma.

Le PV; Tan O; Chopra V; Francis BA; Ragab O; Varma R; Huang D

2013-06-01

340

MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4).  

UK PubMed Central (United Kingdom)

PURPOSE: We investigated the miRNA profile in peripheral nerve tumors and clarified the involvement of miRNA in the development and progression of MPNST in comparison with neurofibroma (NF). In addition, we attempted to seek associations between the miRNA and their potential targets in MPNST. METHODS: Global miRNA expression profiling was investigated for clinical samples of 6 MPNSTs and 6 NFs. As detected by profiling analysis, the expressions of miR-21 in clinical samples of 12 MPNSTs, 11 NFs, and 5 normal nerves, and 3 MPNST cell lines were compared using quantitative real-time reverse transcription PCR. MPNST cell line (YST-1) was transfected with miR-21 inhibitor to study its effects on cell proliferation, caspase activity, and the expression of miR-21 targets. RESULTS: Analysis of miRNA expression profiles in MPNST and NF revealed significantly altered expression levels of nine miRNAs, one of those, miR-21, and its putative target, programmed cell death protein 4 (PDCD4), were selected for further studies. miR-21 expression level in MPNST was significantly higher than that in NF (P < 0.05). In MPNST cells, transfection of miR-21 inhibitor significantly increased caspase activity (P < 0.01), significantly suppressed cell growth (P < 0.05), and upregulated protein level of PDCD4, indicating that miR-21 inhibitor could induce cell apoptosis of MPNST cells. CONCLUSIONS: These results suggest that miR-21 plays an important role in MPNST tumorigenesis and progression through its target, PDCD4. MiR-21 and PDCD4 may be candidate novel therapeutic targets against the development or progression of MPNSTs.

Itani S; Kunisada T; Morimoto Y; Yoshida A; Sasaki T; Ito S; Ouchida M; Sugihara S; Shimizu K; Ozaki T

2012-09-01