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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  

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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.

Kanje Martin

2011-01-01

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

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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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Nerve growth factor activation of the TrkA receptor induces cell death, by macropinocytosis, in medulloblastoma Daoy cells.  

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Ectopic expression of the TrkA receptor tyrosine kinase in tumors of the nervous system can mediate nerve growth factor (NGF)-dependent cell death by apoptosis and /or autophagy. Herein, we demonstrate that TrkA can also induce cell death in medulloblastoma Daoy cells by a caspase-independent mechanism that involves the hyperstimulation of macropinocytosis. Specifically, NGF-stimulates the uptake of AlexaFluor546-dextran into lysosome-associated membrane protein-1 positive vacuoles which fuse with microtubule associated protein light chain 3 (LC3) positive autophagosomes, to form large intracellular vacuoles (> 1 mum), which then fuse with lysotracker positive lysosomes. While LC3 cleavage and the appearance of LC3 positive vacuoles suggest the induction of autophagy, siRNA reduced expression of four proteins essential to autophagy (beclin-1, Atg5, LC3 and Atg9) neither blocks NGF-induced vacuole formation nor cell death. TrkA activated cell death does not require p38, JNK or Erk1/2 kinases but does require activation of class III PI-3 kinase and is blocked by the casein kinase 1 (CK1) inhibitor, D4476. This inhibitor does not interfere with TrkA activation but does block NGF-dependent AlexaFluor546-dextran uptake and CK1 dependent phosphorylation of beta-catenin. Collectively, these data demonstrate that TrkA stimulates cell death by a novel mechanism involving CK1-dependent hyperstimulation of macropinocytosis. PMID:19943845

Li, Chunhui; Macdonald, James I S; Hryciw, Todd; Meakin, Susan O

2010-02-01

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Aurintricarboxylic acid rescues PC12 cells and sympathetic neurons from cell death caused by nerve growth factor deprivation: correlation with suppression of endonuclease activity  

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Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the neuronal cell death which occurs after neurotrophic factor deprivation. In this experimental paradigm, nerve growth factor (NGF) rescues the cells from death. It is reported here that serum-deprived PC12 cells manifest an endonuclease activity that leads to internucleosomal cleavage of their cellular DNA. This activity is detected within 3 h of serum withdrawal and several hours before an...

1991-01-01

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

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

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

2000-01-01

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

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

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

2012-01-01

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Pharmacology of airway afferent nerve activity  

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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 te...

Undem Bradley J; Carr Michael J

2001-01-01

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Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones.  

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Recent evidence suggests that nerve growth factor (NGF), in addition to its neurotrophic functions, acts as an immunomodulator mediating "cross-talk" between neuronal and immune cells, including T lymphocytes. We have analyzed murine CD4+ T-cell clones for their ability to express transcripts encoding NGF, low-affinity NGF receptor, and trk protooncogene, the signal-transducing receptor subunit for NGF. We show that two CD4+ T-helper (Th) clones, Th0-type clone 8/37 and Th2-type clone D10.G4....

Ehrhard, P. B.; Erb, P.; Graumann, U.; Otten, U.

1993-01-01

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

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The aqueous humor (AH) component transforming growth factor (TGF)-?2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary ocular cells. Here we present osteopontin (OPN) as a new TGF-?2 responsive factor in cultured human optic nerve head (ONH) astrocytes. Activation was initially demonstrated by Oligo GEArray microarray and confirmed by semiquantitative (sq) RT-PCR, realtime RT-PCR and western blot. Expressions of most prevalent OPN receptors CD44 and integrin receptor subunits ?V, ?4, ? 5, ?6, ?9, ?1, ?3 and ?5 by ONH astrocytes were shown by sqRT-PCR and immunofluorescence labeling. TGF-?2 treatment did not affect their expression levels. OPN did not regulate gene expression of described TGF-?2 targets shown by sqRT-PCR. In MTS-assays, OPN had a time- and dose-dependent stimulating effect on the metabolic activity of ONH astrocytes, whereas TGF-?2 significantly reduced metabolism. OPN signaling via CD44 mediated a repressive outcome on metabolic activity, whereas signaling via integrin receptors resulted in a pro-metabolic effect. In summary, our findings characterize OPN as a TGF-?2 responsive factor that is not involved in TGF-?2 mediated ECM and HSP modulation, but affects the metabolic activity of astrocytes. A potential involvement in a protective response to TGF-?2 triggered damage is indicated, but requires further investigation. PMID:24718314

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

2014-01-01

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

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The aqueous humor (AH) component transforming growth factor (TGF)-?2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary ocular cells. Here we present osteopontin (OPN) as a new TGF-?2 responsive factor in cultured human optic nerve head (ONH) astrocytes. Activation was initially demonstrated by Oligo GEArray microarray and confirmed by semiquantitative (sq) RT-PCR, realtime RT-PCR and western blot. Expressions of most prevalent OPN receptors CD44 and integrin receptor subunits ?V, ?4, ? 5, ?6, ?9, ?1, ?3 and ?5 by ONH astrocytes were shown by sqRT-PCR and immunofluorescence labeling. TGF-?2 treatment did not affect their expression levels. OPN did not regulate gene expression of described TGF-?2 targets shown by sqRT-PCR. In MTS-assays, OPN had a time- and dose-dependent stimulating effect on the metabolic activity of ONH astrocytes, whereas TGF-?2 significantly reduced metabolism. OPN signaling via CD44 mediated a repressive outcome on metabolic activity, whereas signaling via integrin receptors resulted in a pro-metabolic effect. In summary, our findings characterize OPN as a TGF-?2 responsive factor that is not involved in TGF-?2 mediated ECM and HSP modulation, but affects the metabolic activity of astrocytes. A potential involvement in a protective response to TGF-?2 triggered damage is indicated, but requires further investigation.

Paulsen, Friedrich; Hammer, Christian M.

2014-01-01

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Mast Cell-Nerve Cell Interaction at Acupoint: Modeling Mechanotransduction Pathway Induced by Acupuncture  

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Mast cells are found abundant at sites of acupoints. Nerve cells share perivascular localization with mast cells. Acupuncture (mechanical stimuli) can activate mast cells to release adenosine triphosphate (ATP) which can activate nerve cells and modulates pain-processing pathways in response to acupuncture. In this paper, a mathematical model was constructed for describing intracellular Ca2+ signal and ATP release in a coupled mast cell and nerve cell system induced by mechanical stimuli. The results showed mechanical stimuli lead to a intracellular Ca2+ rise in the mast cell and ATP release, ATP diffuses in the extracellular space (ECS) and activates the nearby nerve cells, then induces electrical current in the nerve cell which spreads in the neural network. This study may facilitate our understanding of the mechanotransduction process induced by acupuncture and provide a methodology for quantitatively analyzing acupuncture treatment.

Yao, Wei; Yang, Hongwei; Yin, Na; Ding, Guanghong

2014-01-01

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Protective activity of aromatic amines and imines against oxidative nerve cell death  

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Oxidative stress is a widespread phenomenon in the pathology of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Neuronal cell death due to oxidative stress may causally contribute to the pathogeneses of these diseases. Therefore, neuroprotective antioxidants are considered to be a promising approach to slow down disease progression. We have investigated different aromatic amine and imine compounds for neuroprotective antioxidant ...

Moosmann, Bernd; Skutella, Thomas; Beyer, Klaus; Behl, Christian

2001-01-01

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Murine oligodendroglial cells express nerve growth factor.  

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The studies reported here present evidence for the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) by an oligodendroglial cell line and of NGF by oligodendrocytes in mouse primary culture. An immortalized oligodendroglial cell line (N19) expressing markers for immature oligodendrocytes stimulated PC12 cells to elaborate processes. Polymerase chain reaction analysis with degenerate primers indicated that the N19 cells expressed the mRNAs for the neurotrophic factors NGF and BDNF. Northern blot analysis confirmed that the N19 cells expressed the 1.3-kb NGF mRNA and the 1.4- and 4-kb BDNF mRNAs. In situ hybridization histochemistry identified the presence of NGF mRNAs in 9-day primary oligodendroglial cultures. Combined immunocytochemistry and in situ hybridization histochemistry colocalized NGF mRNA within primary cultured cells that immunostained for the oligodendrocyte marker galactocerebroside (GC). Double-immunofluorescence analysis also colocalized NGF protein within GC+ cells and within A2B5+ cells, a marker for oligodendrocyte progenitors. These results show that oligodendroglia and their precursor cells can express the neurotrophic factor NGF. They suggest that cells in the oligodendrocyte lineage may play an active role in neurite extension through fiber tracts in addition to myelination. PMID:8090729

Byravan, S; Foster, L M; Phan, T; Verity, A N; Campagnoni, A T

1994-09-13

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

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

Rychkova Natalia

2006-06-01

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

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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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Proliferative effects of melatonin on Schwann cells: implication for nerve regeneration following peripheral nerve injury.  

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Activation of proliferation of Schwann cells is crucial for axonal guidance and successful nerve regeneration following peripheral nerve injury (PNI). Considering melatonin plays an important role in proliferative regulation of central glial cells, the present study determined whether melatonin can effectively promote Schwann cell proliferation and improve nerve regeneration after PNI. The spontaneous immortalized rat Schwann cell line (RSC 96 cells) was first analyzed by quantitative polymerase chain reaction (QPCR) to detect the potential existence of melatonin receptors. The melatonin receptor-mediated signaling responsible for proliferation was examined by measuring the phosphorylation of extracellular signal-regulated kinases (ERK1/2) pathway. The in vivo model of PNI was performed by the end-to-side neurorrhaphy. The quantity of Schwann cells as well as the number of re-innervated motor end plates (MEP) on target muscles was examined to represent the functional recovery of injured nerves. QPCR results indicated that MT1 is the dominant receptor in Schwann cells. Immunoblotting and proliferation assay revealed an enhanced phosphorylation of ERK1/2 and increased number of RSC 96 cells following melatonin administration. Nonselective melatonin receptor antagonist (luzindole) treatment significantly suppressed all the above findings, suggesting that the proliferative effects of melatonin were mediated by a receptor-dependent pathway. In vivo results corresponded well with in vitro findings in which melatonin effectively increased the amount of proliferated Schwann cells and re-innervated MEP on target muscles following PNI. As melatonin successfully improves nerve regeneration by promoting Schwann cell proliferation, therapeutic use of melatonin may thus serve as a promising strategy to counteract the PNI-induced neuronal disability. PMID:24499296

Chang, Hung-Ming; Liu, Chiung-Hui; Hsu, Wen-Ming; Chen, Li-You; Wang, Han-Pin; Wu, Tsung-Huan; Chen, Kuan-Ying; Ho, Wen-Hsin; Liao, Wen-Chieh

2014-04-01

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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.

Ti-Fei Yuan

2010-01-01

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

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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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Murine oligodendroglial cells express nerve growth factor.  

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The studies reported here present evidence for the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) by an oligodendroglial cell line and of NGF by oligodendrocytes in mouse primary culture. An immortalized oligodendroglial cell line (N19) expressing markers for immature oligodendrocytes stimulated PC12 cells to elaborate processes. Polymerase chain reaction analysis with degenerate primers indicated that the N19 cells expressed the mRNAs for the neurotrophi...

Byravan, S.; Foster, L. M.; Phan, T.; Verity, A. N.; Campagnoni, A. T.

1994-01-01

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Regenerative effects of adipose-tissue-derived stem cells for treatment of peripheral nerve injuries.  

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Peripheral nerve injuries are a common occurrence affecting the nerves found outside the central nervous system. Complete nerve transections necessitate surgical re-anastomosis, and, in cases where there is a significant gap between the two ends of the injured nerve, bridging strategies are required to repair the defect. The current clinical gold standard is the nerve graft, but this has a number of limitations, including donor site morbidity. An active area of research is focused on developing other techniques to replace these grafts, by creating tubular nerve-guidance conduits from natural and synthetic materials, which are often supplemented with biological cues such as growth factors and regenerative cells. In the present short review, we focus on the use of adipose-tissue-derived stem cells and the possible mechanisms through which they may exert a positive influence on peripheral nerve regeneration, thereby enabling more effective nerve repair. PMID:24849239

Kolar, Mallappa K; Kingham, Paul J

2014-06-01

 
 
 
 
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Synaptic Activation of Presynaptic Glutamate Transporter Currents in Nerve Terminals  

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Glutamate uptake by high-affinity transporters is responsible for limiting the activation of postsynaptic receptors and maintaining low levels of ambient glutamate. The reuptake process generates membrane currents, which can be activated by synaptically released glutamate in glial cells and some postsynaptic neurons. However, less is known about presynaptic transporter currents because the small size of synaptic boutons precludes direct recordings. Here, we have recorded from two giant nerve ...

Palmer, Mary J.; Taschenberger, Holger; Hull, Court; Tremere, Liisa; Von Gersdorff, Henrique

2003-01-01

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Postganglionic nerve cell bodies and neurotransmitter localization in the teleost heart.  

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A study was undertaken to determine the distribution of specific types of autonomic nerves and the presence of various transmitter substances in the heart of two teleost species: the mullet (Mugil cephalus) and the Nile catfish (Synodontis nigriventris). Large nerve trunks in the sinus venosus were shown to contain tyrosine hydroxylase immunoreactivity and indicate the location of adrenergic nerve fibers, which are also associated with a coronary circulation to the ventricular myocardium in the mullet heart. Fluorescence immunolabelling methods revealed that the atrium and the outer and inner compact muscle of the ventricle have nerves in which substance P and galanin (GA) are localized. It seems likely that the cell bodies (perikarya) of the substance P and GA-immunopositive axons are located at sites outside the heart. The GA-immunopositive nerve fibers may represent a population of axons of intramural postganglionic nerve cell bodies. Most intracardiac nerve cell bodies are located in the sinus venosus and in the sinoatrial junction and reveal immunoreactivity to substance P, GA, neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP). Furthermore, substance P immunoreactivity is present in the cardiac cells intermingled with the substance P-immunopositive nerve fibers. A nerve plexus consisting of a well-developed network of nerve fibers and nerve cell bodies may possibly correspond to a cardiac pacemaker, but its function in fish cardiac regulation is unknown and remains to be elucidated. PMID:19493562

Zaccone, Giacomo; Mauceri, Angela; Maisano, Maria; Giannetto, Alessia; Parrino, Vincenzo; Fasulo, Salvatore

2010-07-01

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Sciatic nerve regeneration by cocultured Schwann cells and stem cells on microporous nerve conduits.  

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Cell transplantation is a useful therapy for treating peripheral nerve injuries. The clinical use of Schwann cells (SCs), however, is limited because of their limited availability. An emerging solution to promote nerve regeneration is to apply injured nerves with stem cells derived from various tissues. In this study, different types of allogeneic cells including SCs, adipose-derived adult stem cells (ASCs), dental pulp stem cells (DPSCs), and the combination of SCs with ASCs or DPSCs were seeded on nerve conduits to test their efficacy in repairing a 15-mm-long critical gap defect of rat sciatic nerve. The regeneration capacity and functional recovery were evaluated by the histological staining, electrophysiology, walking track, and functional gait analysis after 8 weeks of implantation. An in vitro study was also performed to verify if the combination of cells led to synergistic neurotrophic effects (NGF, BDNF, and GDNF). Experimental rats receiving conduits seeded with a combination of SCs and ASCs had the greatest functional recovery, as evaluated by the walking track, functional gait, nerve conduction velocity (NCV), and histological analysis. Conduits seeded with cells were always superior to the blank conduits without cells. Regarding NCV and the number of blood vessels, conduits seeded with SCs and DPSCs exhibited better values than those seeded with DPSCs only. Results from the in vitro study confirmed the synergistic NGF production from the coculture of SCs and ASCs. It was concluded that coculture of SCs with ASCs or DPSCs in a conduit promoted peripheral nerve regeneration over a critical gap defect. PMID:23192007

Dai, Lien-Guo; Huang, Guo-Shiang; Hsu, Shan-hui

2013-01-01

24

Sex, death and the (nerve) cell.  

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Men and women not only look different, but they have different risks of multiple diseases like migraine, neurodegenerative disorders or numerous cancers. Even the nerve cells may die in different ways and exhibit different sensitivity to pro-apoptotic factors. Some of the differences can be explained by the action of sex hormones, but the experiments on four core genotype mouse model, in which XX and XY mice can be of either sex showed that not all differences are due to hormones. An example of a disease with no simple explanation of sex bias is Leber hereditary optic neuropathy, a mitochondrial disease with about 4:1 male to female ratio. The apoptotic death of retinal ganglion cells forming an optic disc is a proposed mechanism of the disease pathophysiology. The mechanisms causing different sensitivity of the nerve cells of male and female subjects may be responsible for the gender bias in LHON and merit further studies. PMID:22201999

Tonska, Katarzyna; Bartnik, Ewa

2012-01-01

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Activation of NF-?B in Axons and Schwann cells at Site of Sciatic Nerve Crush and Role in Modulating Axon Regeneration in Adult Rats: Studies with Etanercept  

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An increasing weight of evidence implicates early inflammatory events as inhibitors of functional recovery in both peripheral and central neuropathologies. In this study, we investigated the role of the inflammatory TNF-?/NF-?B axis on events subsequent to sciatic nerve crush injury in rats. Electrophoretic mobility shift assays (EMSA) revealed that within 6 hours post-crush NF-?B DNA binding activity increased significantly in a 1 cm section of sciatic nerve, centered on the crush site. I...

Smith, Darrell; Tweed, Christopher; Fernyhough, Paul; Glazner, Gordon W.

2009-01-01

26

Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury.  

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Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwann-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell marker. Our findings suggest that using a PCL tube filled with MSCs is a good strategy to improve nerve regeneration after a nerve transection in mice. PMID:22646222

Frattini, Flávia; Lopes, Fatima Rosalina Pereira; Almeida, Fernanda Martins; Rodrigues, Rafaela Fintelman; Boldrini, Leonardo Cunha; Tomaz, Marcelo A; Baptista, Abrahão Fontes; Melo, Paulo A; Martinez, Ana Maria Blanco

2012-10-01

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Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study  

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Full Text Available Abstract Background The time required for radiographic union following femoral fracture increases with age in both humans and rats for unknown reasons. Since abnormalities in fracture innervation will slow skeletal healing, we explored whether abnormal mRNA expression of genes related to nerve cell activity in the older rats was associated with the slowing of skeletal repair. Methods Simple, transverse, mid-shaft, femoral fractures with intramedullary rod fixation were induced in anaesthetized female Sprague-Dawley rats at 6, 26, and 52 weeks of age. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, a bony segment, one-third the length of the femur, centered on the fracture site, including the external callus, cortical bone, and marrow elements, was harvested. cRNA was prepared and hybridized to 54 Affymetrix U34A microarrays (3/age/time point. Results The mRNA levels of 62 genes related to neural function were affected by fracture. Of the total, 38 genes were altered by fracture to a similar extent at the three ages. In contrast, eight neural genes showed prolonged down-regulation in the older rats compared to the more rapid return to pre-fracture levels in younger rats. Seven genes were up-regulated by fracture more in the younger rats than in the older rats, while nine genes were up-regulated more in the older rats than in the younger. Conclusions mRNA of 24 nerve-related genes responded differently to fracture in older rats compared to young rats. This differential expression may reflect altered cell function at the fracture site that may be causally related to the slowing of fracture healing with age or may be an effect of the delayed healing.

Meyer Ralph A

2004-08-01

28

DNA repair in mammalian nerve cells  

International Nuclear Information System (INIS)

DNA synthesis in neurons of neocortex of newborn, 14- and 60-day-old rats after gamma-irradiation in vitro of isolated slices is investigated with the determination of labelled predecessor inclusion into nuclear DNA. 20 Gy dose gamma irradiation increases the DNA synthesis intensity in the neurons of all the animal age groups investigated. The induced DNA synthesis in neurons of newborn rats is higher than in the identical cells of 14- and 60-day-old animals. Peculiarities of DNA synthesis in the course of nerve cell differentiation are discussed

1988-01-01

29

Improvement in nerve regeneration through a decellularized nerve graft by supplementation with bone marrow stromal cells in fibrin.  

Science.gov (United States)

Acellular nerve grafting is often inferior as well as an inadequate alternative to autografting for the repair of long gaps in peripheral nerves. Moreover, the injection method is not perfect. During the injection of cells, the syringe can destroy the acellular nerve structure and the limited accumulation of seed cells. To resolve this problem, we constructed a nerve graft by acellular nerve grafting. Bone marrow-mesenchymal stromal cells (BM-MSCs) were affixed with fibrin glue and injected inside or around the graft, which was then used to repair a 15-mm nerve defect in rats. The acellular nerve graft maintained its structure and composition, and its tensile strength was decreased, as determined by two-photon microscopy and a tensile testing device. In vitro, MSCs embedded in fibrin glue survived and secreted growth factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). We repaired 15-mm Sprague-Dawley rat sciatic nerve defects using this nerve graft construction, and MSCs injected around the graft helped improve nerve regeneration and functional recovery of peripheral nerve lesions as determined by functional analysis and histology. Therefore, we conclude that supplying MSCs in fibrin glue around acellular nerves is successful in maintaining the nerve structure and can support nerve regeneration similar to the direct injection of MSCs into the acellular nerve for long nerve defects but may avoid destroying the nerve graft. The technique is simple and is another option for stem cell transplantation. PMID:23128095

Zhao, Zhe; Wang, Yu; Peng, Jiang; Ren, Zhiwu; Zhang, Li; Guo, Quanyi; Xu, Wenjing; Lu, Shibi

2014-01-01

30

Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve.  

Science.gov (United States)

Background:?To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined. Methods and Results:?In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100?g/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7±1.1 to 7.8±0.9nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release. Conclusions:?Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.??(Circ J?2014; 78: 1405-1413). PMID:24727611

Shimizu, Shuji; Akiyama, Tsuyoshi; Kawada, Toru; Kamiya, Atsunori; Turner, Michael James; Yamamoto, Hiromi; Shishido, Toshiaki; Shirai, Mikiyasu; Sugimachi, Masaru

2014-05-23

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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  

Energy Technology Data Exchange (ETDEWEB)

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

Chen, Aiqiong; Du, Dan; Lin, Yuehe

2012-02-09

32

Axonal transport of adenylate cyclase activity in normal and axotomized frog sciatic nerve.  

Science.gov (United States)

Adenylate cyclase activity accumulated proximal to a constriction placed around the frog sciatic nerve. The rate of accumulation was linear between 8 and 24 h following placement of the constriction; accumulation rate declined substantially after 24 h. Accumulation of activity distal to the constriction in normal nerve was not significantly different from control for the first 72 h, but increased at 5 days. These data are interpreted as indicating that adenylate cyclase is transported from the cell body to the nerve terminals in normal frog nerve, but not in the reverse direction. Following axon transection, anterograde transport of adenylate cyclase activity declined, but a transient retrograde transport of adenylate cyclase activity appeared. In addition, adenylate cyclase activity accumulated in the proximal transected nerve stump during the period when Schwann cell proliferation and the initiation of nerve regeneration both appear. The pattern of response of adenylate cyclase activity to nerve injury suggests that the adenylate cyclase: cAMP system could play some role in peripheral nerve regeneration. PMID:6200180

Carlsen, R C

1982-01-28

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

Science.gov (United States)

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. PMID:24041294

Biazar, Esmaeil; Heidari Keshel, Saeed; Pouya, Majid

2013-10-01

34

Nerve growth factor modulation of retinal ganglion cell physiology.  

Science.gov (United States)

Nerve growth factor (NGF) is an endogenous neurotrophin involved in the development, maintenance and regeneration of mammalian sympathetic and sensory neurons. Additionally, NGF is known to have trophic and differentiating activity on several populations of cholinergic neurons of the central nervous system (CNS), and to act as a differentiation factor in the development of the visual cortex. The paramount functions of NGF in the visual system are also highlighted by the presence of this neurotrophin and both its receptors TrkA and p75 in most intra-ocular tissues, including lens, vitreous, choroid, iris, and trabecular meshwork. In the retina, NGF is produced and utilized specifically by retinal ganglion cells (RGC), bipolar neurons and glial cells, and is thought to have crucial protective effects in several disease states. Studies on the role of NGF on RGCs survival following optic nerve transection, ischemic injury, ocular hypertension and glaucoma are discussed in this review. PMID:24501088

Roberti, Gloria; Mantelli, Flavio; Macchi, Ilaria; Massaro-Giordano, Mina; Centofanti, Marco

2014-09-01

35

Mathematical and Numerical Analysis of Firing Correlations Between Nerve Cells.  

Science.gov (United States)

An important tool for studying the nervous system is the simultaneous recording of firing activity from individual nerve cells. In this dissertation, both mathematical and numerical models are used to aid the interpretation of data from these experiments. The role played by firing correlations in the collective behavior of nerve cell networks is investigated using an efficient numerical algorithm we have developed expressly for this purpose. The algorithm employs neurons which integrate synaptic input and fire spikes when this sum exceeds a threshold value. The governing dynamical equations are solved to arbitrary precision in continuous time. We show that the firing synchrony within a group of nerve cells can gate the transmission of neurological signals through synaptic pathways. This capability is shown to follow directly from the response characteristics of individual cells. We identify two distinct dynamical regimes. In the first regime firing correlations are not relevant for the collective behavior of the system. In the second regime, however, firing correlations may be of crucial significance. The observed response properties of single nerve cells are then predicted using a stochastic model which we have developed. The model is solved explicitly to first order in perturbation theory using methods that may be directly generalized to the description of more physiologically realistic neurons. These models may be used to better estimate physical parameters from the experimental data and to develop analytical models of nerve cell networks which incorporate realistic synaptic interactions. We also study stochastic models of reduced networks, which usually consist of a few recorded cells embedded in a much larger surrounding population. The firing of each recorded cell is assumed to be a Markov process which depends only on the input from other cells in the reduced network. These models are used to derive new theoretical relationships between experimental quantities which are then verified using numerical simulations. To accomplish this a new method for analyzing spike train data is introduced and two new experimental quantities, the frequency correlation function and the spike train entropy, are defined. Their efficient computation from the spike train data is also described. Finally, linear stochastic models are analyzed which permit an exact solution for various experimental quantities. We derive an approximate version of the fluctuation -dissipation theorem, which may be applied to the analysis of spike train data from a single cell. We also solve the model for translationally invariant network architectures, for which the model predicts the diverging correlation times observed at critical parameter values.

Kenyon, Garrett Taylor

1990-01-01

36

Scanning electron microscopy of the attachment of Treponema pallidum to nerve cells in vitro.  

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Treponema pallidum (Nichols strain) was incubated with cultured nerve cells derived from rat embryos. Primary cultures were established from dorsal root ganglia, superior cervical ganglia, and spinal cord. Using phase contrast microscopy treponemes were seen to interact with the nerve cells in a similar manner to other cultured mammalian cells. Organisms began to attach within minutes after inoculation, actively motile organisms attached at the tip of one end, higher numbers of organisms atta...

Repesh, L. A.; Fitzgerald, T. J.; Oakes, S. G.; Pozos, R. S.

1982-01-01

37

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

38

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%. 

Nanik Suciati

2012-07-01

39

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%.

Nanik Suciati

2012-09-01

40

A nerve graft constructed with xenogeneic acellular nerve matrix and autologous adipose-derived mesenchymal stem cells.  

Science.gov (United States)

Since synthetic nerve conduits do not exhibit the characteristics of regeneration, they are generally inadequate substitutes for autologous nerve graft in the repair of long peripheral nerve defects. To resolve this problem, in this study, we constructed a nerve regeneration characteristics-containing nerve graft through integrating xenogeneic acellular nerve matrix (ANM) with autologous neural differentiated adipose-derived mesenchymal stem cells (ADSCs). Xenogeneic ANM was processed by a protocol removing cells and myelin sheath completely, meanwhile preserving growth factors and extracellular matrix (ECM) microstructure of natural nerve, such as porous and basal lamina tube. Cytocompatibility and immunocompatibility evaluation revealed that ANM could support cell attachment and proliferation, and did not stimulate vigorous host reject response. After inoculation of neural differentiated ADSCs onto ANM, differentiated cells were observed to align along longitudinal axis of ANM, resembling band of büngner, and persistently express NGF, GDNF, and BDNF. In vivo, neural differentiated ADSCs also presented glial cell characteristics and promote nerve regeneration 7 days post transplantation. We repaired 1cm Sprague Dawley rat sciatic nerve defects using this nerve graft construction and nerve gap regeneration was indicated by electrophysiology, retrograde labeling and histology analysis. Therefore, we conclude that constructed nerve graft, offering nerve regeneration characteristics, hold great promise to replace autologous in repair peripheral nerve defect. PMID:20381139

Zhang, Yongjie; Luo, Hailang; Zhang, Ziqiang; Lu, Yongbo; Huang, Xinhui; Yang, Lu; Xu, Jiajie; Yang, Wei; Fan, Xiaoju; Du, Bing; Gao, Peng; Hu, Gang; Jin, Yan

2010-07-01

 
 
 
 
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NFAT is a nerve activity sensor in skeletal muscle and controls activity-dependent myosin switching  

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Calcineurin (Cn) signaling has been implicated in nerve activity-dependent fiber type specification in skeletal muscle, but the downstream effector pathway has not been established. We have investigated the role of the transcription factor nuclear factor of activated T cells (NFAT), a major target of Cn, by using an in vivo transfection approach in regenerating and adult rat muscles. NFAT transcriptional activity was monitored with two different NFAT-dependent reporters and was found to be hi...

2004-01-01

42

Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair.  

Science.gov (United States)

A basic experiment of peripheral nerve regeneration using neuronal progenitor cells embedded in collagen gel was performed in a rat sciatic nerve defect. First, when neuronal progenitor cells derived from the fetal rat hippocampus were cultured in atelocollagen-containing medium, neurospheres positive for anti-nestin antibody were confirmed after 8 days. These cells differentiated into astrocytes positive for anti-glial fibrillary acidic protein (GFAP) antibody, oligodendrocytes positive for anti-galactocerebroside (GalC) antibody and neurons positive for anti-neurofilament 200 (NF200) antibody, and they were capable of extending axons. They also differentiated into Schwann-like supportive cells positive for anti-s100 and anti-p75 antibody. Next, a 15-mm defect was prepared in the sciatic nerve of mature rats, and the nerve was bridged with a silicone tube filled with neuronal progenitor cells (1 x 10(5)) embedded in collagen gel. The transplanted neuronal progenitor cells were labeled in advance with 5-bromo-2-deoxyuridine (BrdU). When the regenerated tissue was examined 6 weeks and 10 weeks after grafting, the number and diameter of myelinated fibers were significantly increased compared with a control tube without neuronal progenitor cells. Action potentials were detected in the regenerated nerve. Also, cells positive for both anti-BrdU antibody and anti-S100 or anti-p75 antibody were observed in the regenerated tissue, and part of the grafted neural stem cells were considered to have differentiated into Schwann cell-like supportive cells. From these results neuronal progenitor cells derived from the fetal rat hippocampus are considered to retain their proliferative and differentiating abilities in collagen gel, and when transplanted to a site of peripheral nerve defect, part of them differentiate into supportive cells and they contributed to promotion of axonal regeneration. PMID:12742620

Murakami, Takeshi; Fujimoto, Yoshinori; Yasunaga, Yuji; Ishida, Osamu; Tanaka, Nobuhiro; Ikuta, Yoshikazu; Ochi, Mitsuo

2003-06-01

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c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.  

Science.gov (United States)

The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue. PMID:22920255

Arthur-Farraj, Peter J; Latouche, Morwena; Wilton, Daniel K; Quintes, Susanne; Chabrol, Elodie; Banerjee, Ambily; Woodhoo, Ashwin; Jenkins, Billy; Rahman, Mary; Turmaine, Mark; Wicher, Grzegorz K; Mitter, Richard; Greensmith, Linda; Behrens, Axel; Raivich, Gennadij; Mirsky, Rhona; Jessen, Kristján R

2012-08-23

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c-Jun Reprograms Schwann Cells of Injured Nerves to Generate a Repair Cell Essential for Regeneration  

Science.gov (United States)

Summary The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue.

Arthur-Farraj, Peter J.; Latouche, Morwena; Wilton, Daniel K.; Quintes, Susanne; Chabrol, Elodie; Banerjee, Ambily; Woodhoo, Ashwin; Jenkins, Billy; Rahman, Mary; Turmaine, Mark; Wicher, Grzegorz K.; Mitter, Richard; Greensmith, Linda; Behrens, Axel; Raivich, Gennadij; Mirsky, Rhona; Jessen, Kristjan R.

2012-01-01

45

Exposure to Nerve Growth Factor Worsens Nephrotoxic Effect Induced by Cyclosporine A in HK-2 Cells  

Science.gov (United States)

Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkANTR and p75NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.

Lofaro, Danilo; Toteda, Giuseppina; Lupinacci, Simona; Leone, Francesca; Gigliotti, Paolo; Papalia, Teresa; Bonofiglio, Renzo

2013-01-01

46

Roles of meltrin-beta/ADAM19 in progression of Schwann cell differentiation and myelination during sciatic nerve regeneration.  

Science.gov (United States)

Remyelination is an important aspect of nerve regeneration after nerve injury, but the underlying mechanisms are not fully understood. Here, we show that meltrin-beta (ADAM19), a member of the ADAM (a disintegrin and metalloprotease) family, plays crucial roles in nerve regeneration after a crush injury to the sciatic nerves. The expression of meltrin-beta was up-regulated in neurons after the crush injury. Morphometrical analysis revealed a delay in remyelination in meltrin-beta-deficient nerves, whereas no significant defects were observed in their axon elongation. The activation of Krox-20, an indispensable transcription factor for myelination, was delayed in meltrin-beta-deficient nerves and was accompanied by the retarded expression of myelin-related proteins. Expression of Krox-20 in Schwann cells was mediated by Akt. Phosphorylation of Akt but not that of Erks was reduced in regenerating nerves of meltrin-beta-deficient mice. The cell membrane fraction prepared from meltrin-beta-deficient nerves showed a defective activation of Akt in the membrane-loaded Schwann cells. Meltrin-beta-deficient mice exhibited delayed sciatic functional recovery after the nerve crush. Altogether, these results reveal a role of meltrin-beta in Schwann cell differentiation and re-myelination in nerve regeneration. Moreover, this study suggests that meltrin-beta functions as a modulator of juxtacrine signaling from axons that activate the Akt pathway and the Krox-20 expression, which is the prerequisite for Schwann cell differentiation. PMID:19049978

Wakatsuki, Shuji; Yumoto, Norihiro; Komatsu, Koji; Araki, Toshiyuki; Sehara-Fujisawa, Atsuko

2009-01-30

47

Low-dose methotrexate reduces peripheral nerve injury-evoked spinal microglial activation and neuropathic pain behavior in rats  

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Peripheral nerve injuries that provoke neuropathic pain are associated with microglial activation in the spinal cord. We have investigated the characteristics of spinal microglial activation in three distinct models of peripheral neuropathic pain: spared nerve injury (SNI), chronic constriction injury, and spinal nerve ligation. In all models, dense clusters of cells immunoreactive for the microglial marker CD11b formed in the ipsilateral dorsal horn 7 days after injury. Microglial expression...

Scholz, Joachim; Abele, Andrea; Marian, Claudiu; Ha?ussler, Annett; Herbert, Teri A.; Woolf, Clifford J.; Tegeder, Irmgard

2008-01-01

48

Mechanical activity of frog esophagus muscle in response to electrical stimulation of intramural nerves.  

Science.gov (United States)

Microscopic observation of intramural nerves in the frog esophagus, fixed and stained with OsO(4) and ZnI(2), revealed that nerve cell bodies and bundles connecting the nerve cell bodies formed loose and irregular networks. The nerve cell bodies were mostly lying singly in the nerve bundles, with occasional observations of two closely linked nerve cell bodies. Isolated circular and longitudinal segments of esophageal muscle were spontaneously rhythmically contractile, with a frequency of 2.2-3.0 per min. This was not altered by tetrodotoxin (TTX). In longitudinal muscle segments, transmurally applied electrical stimulation produced contractile responses which were not inhibited by atropine or guanethidine, but were reduced in amplitude by TTX, suggesting a nonadrenergic-noncholinergic (NANC) excitatory innervation in the esophagus muscle. In circular muscle segments, transmural application of brief electrical stimulation evoked two types of mechanical response: a biphasic response consisting of an initial relaxation and a following contraction (type I) and a contraction alone (type II). These mechanical responses were not modulated by either atropine or guanethidine. In the type I response, TTX abolished the relaxation component, suggesting that this was produced by non-adrenergic non-cholinergic (NANC) inhibitory nerve excitation. In about half of the type II responses, the amplitude of the contraction was significantly reduced by TTX, suggesting that a part of the contraction was produced by activation of NANC excitatory nerves. Thus, the esophageal smooth muscle of the frog demonstrates myogenic activity, and is innervated by both excitatory and inhibitory NANC nerves. PMID:17598959

Yoshida, Masahide

2007-04-01

49

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

2005-11-01

50

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

Science.gov (United States)

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

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

2014-06-20

51

Motor neuron activation in peripheral nerves using infrared neural stimulation  

Science.gov (United States)

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

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

2014-02-01

52

Variable Patterned Pudendal Nerve Stimuli Improves Reflex Bladder Activation  

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

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

2008-01-01

53

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

Science.gov (United States)

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. PMID:23899526

Nakamura, Mami; Inoh, Yoshikazu; Nakanishi, Mamoru; Furuno, Tadahide

2013-08-30

54

Preferential and comprehensive reconstitution of severely damaged sciatic nerve using murine skeletal muscle-derived multipotent stem cells.  

Science.gov (United States)

Loss of vital functions in the somatic motor and sensory nervous systems can be induced by severe peripheral nerve transection with a long gap following trauma. In such cases, autologous nerve grafts have been used as the gold standard, with the expectation of activation and proliferation of graft-concomitant Schwann cells associated with their paracrine effects. However, there are a limited number of suitable sites available for harvesting of nerve autografts due to the unavoidable sacrifice of other healthy functions. To overcome this problem, the potential of skeletal muscle-derived multipotent stem cells (Sk-MSCs) was examined as a novel alternative cell source for peripheral nerve regeneration. Cultured/expanded Sk-MSCs were injected into severely crushed sciatic nerve corresponding to serious neurotmesis. After 4 weeks, engrafted Sk-MSCs preferentially differentiated into not only Schwann cells, but also perineurial/endoneurial cells, and formed myelin sheath and perineurium/endoneurium, encircling the regenerated axons. Increased vascular formation was also observed, leading to a favorable blood supply and waste product excretion. In addition, engrafted cells expressed key neurotrophic and nerve/vascular growth factor mRNAs; thus, endocrine/paracrine effects for the donor/recipient cells were also expected. Interestingly, skeletal myogenic capacity of expanded Sk-MSCs was clearly diminished in peripheral nerve niche. The same differentiation and tissue reconstitution capacity of Sk-MSCs was sufficiently exerted in the long nerve gap bridging the acellular conduit, which facilitated nerve regeneration/reconnection. These effects represent favorable functional recovery in Sk-MSC-treated mice, as demonstrated by good corduroy walking. We also demonstrated that these differentiation characteristics of the Sk-MSCs were comparable to native peripheral nerve-derived cells, whereas the therapeutic capacities were largely superior in Sk-MSCs. Therefore, Sk-MSCs can be a novel/suitable alternative cell source for healthy nerve autografts. PMID:24614849

Tamaki, Tetsuro; Hirata, Maki; Soeda, Shuichi; Nakajima, Nobuyuki; Saito, Kosuke; Nakazato, Kenei; Okada, Yoshinori; Hashimoto, Hiroyuki; Uchiyama, Yoshiyasu; Mochida, Joji

2014-01-01

55

Preferential and Comprehensive Reconstitution of Severely Damaged Sciatic Nerve Using Murine Skeletal Muscle-Derived Multipotent Stem Cells  

Science.gov (United States)

Loss of vital functions in the somatic motor and sensory nervous systems can be induced by severe peripheral nerve transection with a long gap following trauma. In such cases, autologous nerve grafts have been used as the gold standard, with the expectation of activation and proliferation of graft-concomitant Schwann cells associated with their paracrine effects. However, there are a limited number of suitable sites available for harvesting of nerve autografts due to the unavoidable sacrifice of other healthy functions. To overcome this problem, the potential of skeletal muscle-derived multipotent stem cells (Sk-MSCs) was examined as a novel alternative cell source for peripheral nerve regeneration. Cultured/expanded Sk-MSCs were injected into severely crushed sciatic nerve corresponding to serious neurotmesis. After 4 weeks, engrafted Sk-MSCs preferentially differentiated into not only Schwann cells, but also perineurial/endoneurial cells, and formed myelin sheath and perineurium/endoneurium, encircling the regenerated axons. Increased vascular formation was also observed, leading to a favorable blood supply and waste product excretion. In addition, engrafted cells expressed key neurotrophic and nerve/vascular growth factor mRNAs; thus, endocrine/paracrine effects for the donor/recipient cells were also expected. Interestingly, skeletal myogenic capacity of expanded Sk-MSCs was clearly diminished in peripheral nerve niche. The same differentiation and tissue reconstitution capacity of Sk-MSCs was sufficiently exerted in the long nerve gap bridging the acellular conduit, which facilitated nerve regeneration/reconnection. These effects represent favorable functional recovery in Sk-MSC-treated mice, as demonstrated by good corduroy walking. We also demonstrated that these differentiation characteristics of the Sk-MSCs were comparable to native peripheral nerve-derived cells, whereas the therapeutic capacities were largely superior in Sk-MSCs. Therefore, Sk-MSCs can be a novel/suitable alternative cell source for healthy nerve autografts.

Tamaki, Tetsuro; Hirata, Maki; Soeda, Shuichi; Nakajima, Nobuyuki; Saito, Kosuke; Nakazato, Kenei; Okada, Yoshinori; Hashimoto, Hiroyuki; Uchiyama, Yoshiyasu; Mochida, Joji

2014-01-01

56

Nerve gap repair by the use of artificial conduits and cultured cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. This thesis investigates the use of fibrin as both a tubular conduit to guide nerve regeneration and also as a matrix material to suspend various regenerative cell types within/on poly-3-hydroxybutyrate (PHB) nerve conduits. Adipose derived stem cells (ASC) are found in abundant quantities. In this thesis the ability of rat ASC to diff...

Kalbermatten, Daniel

2010-01-01

57

Mechanisms of insulin action on sympathetic nerve activity  

Science.gov (United States)

Insulin resistance and hyperinsulinemia may contribute to the development of arterial hypertension. Although insulin may elevate arterial pressure, in part, through activation of the sympathetic nervous system, the sites and mechanisms of insulin-induced sympathetic excitation remain uncertain. While sympathoexcitation during insulin may be mediated by the baroreflex, or by modulation of norepinephrine release from sympathetic nerve endings, it has been shown repeatedly that insulin increases sympathetic outflow by actions on the central nervous system. Previous studies employing norepinephrine turnover have suggested that insulin causes sympathoexcitation by acting in the hypothalamus. Recent experiments from our laboratory involving direct measurements of regional sympathetic nerve activity have provided further evidence that insulin acts in the central nervous system. For example, administration of insulin into the third cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve activity in normotensive rats. Interestingly, this pattern of regional sympathetic nerve responses to central neural administration of insulin is similar to that seen with systemic administration of insulin. Further, lesions of the anteroventral third ventricle hypothalamic (AV3V) region abolished increases in sympathetic activity to systemic administration of insulin with euglycemic clamp, suggesting that AV3V-related structures are critical for insulin-induced elevations in sympathetic outflow.

Muntzel, Martin S.; Anderson, Erling A.; Johnson, Alan Kim; Mark, Allyn L.

1996-01-01

58

Regenerative effect of adipose tissue-derived stem cells transplantation using nerve conduit therapy on sciatic nerve injury in rats.  

Science.gov (United States)

This study proposed a biodegradable GGT nerve conduit containing genipin crosslinked gelatin annexed with tricalcium phosphate (TCP) ceramic particles for the regeneration of peripheral nerves. Cytotoxicity tests revealed that GGT-extracts were non-toxic and promoted proliferation and neuronal differentiation in the induction of stem cells (i-ASCs) derived from adipose tissue. Furthermore, the study confirmed the effectiveness of a GGT/i-ASCs nerve conduit as a guidance channel in the repair of a 10-mm gap in the sciatic nerve of rats. At eight weeks post-implantation, walking track analysis showed a significantly higher sciatic function index (SFI) (P?nerve tissue at the site of implantation was observed in either group. Histological observation and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/i-ASCs nerve conduits were similar to those of the autografts. These promising results achieved through a combination of regenerative cells and GGT nerve conduits suggest the potential value in the future development of clinical applications for the treatment of peripheral nerve injury. PMID:22552954

Liu, Bai-Shuan; Yang, Yi-Chin; Shen, Chiung-Chyi

2014-05-01

59

Brain Lipid Binding Protein in Axon-Schwann Cell Interactions and Peripheral Nerve Tumorigenesis  

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Loss of axonal contact characterizes Schwann cells in benign and malignant peripheral nerve sheath tumors (MPNST) from neurofibromatosis type 1 (NF1) patients. Tumor Schwann cells demonstrate NF1 mutations, elevated Ras activity, and aberrant epidermal growth factor receptor (EGFR) expression. Using cDNA microarrays, we found that brain lipid binding protein (BLBP) is elevated in an EGFR-positive subpopulation of Nf1 mutant mouse Schwann cells (Nf1?/? TXF) that grows away from axons; BLBP...

Miller, Shyra J.; Li, Hongzhen; Rizvi, Tilat A.; Huang, Yuan; Johansson, Gunnar; Bowersock, Jason; Sidani, Amer; Vitullo, John; Vogel, Kristine; Parysek, Linda M.; Declue, Jeffrey E.; Ratner, Nancy

2003-01-01

60

Fast optical response to electrical activation in peripheral nerves  

Science.gov (United States)

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

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

2007-03-01

 
 
 
 
61

Localization and control of activity in peripheral nerves.  

Science.gov (United States)

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

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

2008-01-01

62

[Electric activity of vagus nerve in rats according to satiety].  

Science.gov (United States)

Vagus nerve as a part of brain-gut axis transmits peripheral information to the brain via vagovagal reflexes. Electric properties of the vagus are not exactly known. Analysis of electric changes in vagal nerves evoked by physiologic impulse such as stomach distention by food would facilitate applying better documented and therefore safer vagal neuromodulation. The aim of our study was analysis and interpretation of electric properties of the left vagus in vivo in fasted and satiated Wistar rats. Silver measuring electrodes connected to analog amplifier (A-M Systems 3000) were attached to the nerve in the neck region. The signal was filtered and probing by computer recording system (ADInstruments Power Lab) and additional analyses were performed using GNU Octave programme. Our resuts have shown that the higher amplitude the smaller number of counted impulses in the vagus was detected. This relationship was true only till the maximum level typical for each recording (about 15-20 dB). We note that observed inter spike interval can be approximated with log-normal distribution, and that its mu parameter is enough to characterize a particular recording. Satiated rats were characterized by higher number of spikes per second in the nerve than fasted ones (0.9 vs 0.26) indicating that food intake increased nervous activity 3-4 times comparing to fasted state. The outcomes encourage us to state that good quality characteristic of the left vagus nerve activity provides an effective tool for detection of peripheral signals which are transmitting via vagal afferents to the higher centres. Target vagal neuromodulation to obtain certain terapeutic effects may be possible. PMID:22891533

Zaraska, Krzysztof; Ziomber, Agata; Ciesielczyk, Katarzyna; Bugajski, Andrzej; Wi?niewska, Olga; Skowron, Beata; Juszczak, Kajetan; Zaraska, Wies?aw; Thor, Piotr J

2011-01-01

63

A nanofibrous PHBV tube with Schwann cell as artificial nerve graft contributing to rat sciatic nerve regeneration across a 30-mm defect bridge.  

Science.gov (United States)

A nanofibrous PHBV nerve conduit has been used to evaluate its efficiency based on the promotion of nerve regeneration in rats. The designed conduits were investigated by physical, mechanical and microscopic analyses. The conduits were implanted into a 30-mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently high mechanical properties to serve as a nerve guide. The results demonstrated that in the nanofibrous graft with cells, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. For the grafts especially the nanofibrous conduits with cells, muscle cells of gastrocnemius on the operated side were uniform in their size and structures. This study proves the feasibility of artificial conduit with Schwann cells for nerve regeneration by bridging a longer defect in a rat model. PMID:23461795

Biazar, Esmaeil; Heidari Keshel, Saeed

2013-02-01

64

Microglial/macrophage cells in mammalian olfactory nerve fascicles.  

Science.gov (United States)

This is the first description of a population of Iba1- and annexin A3-immunopositive cells residing in the peripheral olfactory nerves of adult rats and adult cats. Based on their ramified appearance, positive immunostaining for the monocytic markers Iba1 and annexin A3, and reactivity to bulbectomy (in adult rats), these cells found within the olfactory nerve fascicles of both mammalian species meet several important criteria for their designation as microglia/macrophages. These Iba1-/annexin A3-immunopositive cells may be uniquely positioned to protect against the potential spread of dangerous environmental xenobiotics (such as viruses and toxins) into the brain, where such pathogens may contribute to the development of neurological diseases, such Alzheimer's and Parkinson's diseases. PMID:19830837

Smithson, Laura J; Kawaja, Michael D

2010-03-01

65

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

Science.gov (United States)

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

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

2014-03-01

66

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

Science.gov (United States)

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

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

1999-01-01

67

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2011-01-01

68

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

69

Membrane phosphorylation and nerve cell function  

International Nuclear Information System (INIS)

This thesis deals with the phosphorylation of membrane components. In part I a series of experiments is described using the hippocampal slice as a model system. In part II a different model system - cultured hybrid cells - is used to study protein and lipid phosphorylation, influenced by incubation with neuropeptides. In part III in vivo and in vitro studies are combined to study protein phosphorylation after neuroanatomical lesions. In a section of part II (Page 81-90) labelling experiments of the membrane inositol-phospholipids are described. 32P-ATP was used to label phospholipids in intact hybrid cells, and short incubations were found to be the most favourable. (C.F.)

1982-01-01

70

Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using...

Jonsson, Samuel; Wiberg, Rebecca; Mcgrath, Aleksandra M.; Novikov, Lev N.; Wiberg, Mikael; Novikova, Liudmila N.; Kingham, Paul J.

2013-01-01

71

Effect of Delayed Peripheral Nerve Repair on Nerve Regeneration, Schwann Cell Function and Target Muscle Recovery  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using...

Jonsson, Samuel; Wiberg, Rebecca; Mcgrath, Aleksandra M.; Novikov, Lev N.; Wiberg, Mikael; Novikova, Liudmila N.; Kingham, Paul J.

2013-01-01

72

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Anderson, A. J.; Harvey, A. L.

1988-01-01

73

Electrophysiological Study of Sciatic Nerve Regeneration Through Tubes Seeded with Schwann Cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A B S T R A C TIntroduction: Peripheral nerve injury is a common disorder and leads to permanent neurological defects. Schwann cells have been shown to have nerve repair after being transplanted in peripheral nerve injury. The aim of this study was to determine the beneficial effect of allograft Schwann cells on electrophysiological outcome after transection of the sciatic nerve in rats.Methods: Twenty adult male Wistar rats (200-250 g) were used in this study and left sciatic nerve was cut 1...

Mehrdad Bakhtyari; Hamid Abootaleb; Korosh Mansouri

2010-01-01

74

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. PMID:23733515

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

2014-05-01

75

Nerve growth factor-mediated targeting of liposomes to cells  

International Nuclear Information System (INIS)

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

1986-05-01

76

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2010-01-01

77

Comparative characteristic of thiamine antagonists on apoptosis induction in different types of nerve cell lines.  

Science.gov (United States)

Abnormalities in oxidative metabolism and inflammation accompany many neurodegenerative diseases. The mechanisms of neurodegeneration induced by thiamine deficiency remain incompletely elucidated. The susceptibility of various types of nerve cells to thiamine (vitamin B) antagonists--oxythiamine (OT), pyrithiamine (PT) and amprolium (Am) was investigated. Four cell lines (neuronally differentiated rat PC-12, rat astrocytes DITNC, neuronally differentiated human SH-SY5Y and human astrocytic cells 1321N1) were used for experiments as neural cell models. When different cell types were cultivated with thiamine antagonists, a significant decrease of viability was detected in a time- and dose-dependent manner as demonstrated by the WST-1 colorimetric assay. These data were similar to those of caspase 3 activity and DNA fragmentation induced by thiamine antagonists. All tested cell lines were more vulnerable to OT and PT than to Am. Am displayed a pronounced damaging action on neuronal cells and had a modest influence on astrocytes. The last observation gives the basis to suppose, that neuronal cells need external arrival of thiamine more than astrocytes. Thus, the results testify that various types of nerve cells have different susceptibility to the thiamine antagonists and this relates to extent of apoptosis development. PMID:19248620

Chornyy, S A; Parkhomenko, Yu M

2008-01-01

78

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  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells and
optic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinal
ganglion 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% of
cases presented HIF-1 expressi...

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

2012-01-01

79

Evidence for GABAB-mediated inhibition of transmission from the olfactory nerve to mitral cells in the rat olfactory bulb.  

Science.gov (United States)

The GABAB agonist baclofen blocks transmission from the olfactory nerve to second order neurons in the frog olfactory bulb, and GABAB receptors in the rat olfactory bulb are selectively located in the glomerular layer. A reasonable hypothesis, therefore, is that inhibition in the glomerular layer is mediated, at least in part, by GABAB receptors. Here, we investigated the role of GABAB receptors in regulating the responses of mitral cells to activation of the olfactory nerve in the rat. Topical application of baclofen to the surface of the rat olfactory bulb reduced the amplitude of field potentials evoked by olfactory nerve stimulation (orthodromic response). Baclofen reduced the orthodromic response in a dose-dependent manner but the drug had no effect on the field potential evoked by antidromic activation of mitral cell axons (antidromic response). Baclofen also reduced olfactory nerve-evoked responses of mitral cells in an olfactory bulb slice preparation. The pharmacological specificity of the inhibition was confirmed by showing that the GABAB antagonist, CGP 55845A, blocked the inhibitory action of baclofen. These results suggest that transmission from olfactory nerve terminals to second order neurons is negatively regulated by periglomerular GABAergic interneurons; this inhibition is mediated, at least partially, by GABAB receptors. PMID:7953767

Nickell, W T; Behbehani, M M; Shipley, M T

1994-01-01

80

Laser-activated protein solder for peripheral nerve repair  

Science.gov (United States)

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

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

1995-05-01

 
 
 
 
81

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

All transforming growth factor ? (TGF-?) superfamily members are synthesized as precursors with prodomain sequences that are proteolytically removed by subtilisin-like proprotein convertases (SPCs). For most superfamily members, this is believed sufficient for activation. Exceptions are TGF-?s 1 to 3 and growth differentiation factor 8 (GDF8), also known as myostatin, which form noncovalent, latent complexes with their SPC-cleaved prodomains. Sequence similarities between TGF-?s 1 to 3, m...

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

2005-01-01

82

GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells.  

Science.gov (United States)

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

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

2005-07-01

83

Intravenous cyclosporine activates afferent and efferent renal nerves and causes sodium retention in innervated kidneys in rats.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The effect of acute intravenous infusion of cyclosporine (10 mg/kg) on efferent renal and genitofemoral nerve activity and afferent renal nerve activity was studied in anesthetized rats. All animals were studied after unilateral renal denervation and extracellular fluid volume expansion. Activity of both efferent sympathetic nerves was increased significantly by cyclosporine infusion (renal, 69%; genitofemoral, 60%). Afferent renal nerve activity was increased 82% after cyclosporine (P less t...

Moss, N. G.; Powell, S. L.; Falk, R. J.

1985-01-01

84

Laser-activated protein bands for peripheral nerve repair  

Science.gov (United States)

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

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

1996-01-01

85

Perineural spread of squamous cell carcinoma involving trigeminal and facial nerves.  

Science.gov (United States)

Perineural spread of squamous cell carcinomas in the orofacial region predominantly involves the trigeminal and facial nerves. Central spread, particularly along the trigeminal nerve, produces sensory impairment and involvement of other divisions through invasion of the gasserian ganglion, as illustrated in these case reports. Early diagnosis and medical referral is important because central invasion has a poor prognosis. PMID:8488026

Schifter, M; Barrett, A P

1993-05-01

86

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2002-01-01

87

Epidermal expression of Lgr6 is dependent on nerve endings and Schwann cells  

Science.gov (United States)

Lgr5/6 proteins are stem cell markers in various tissues. However, what determines their restricted expression pattern in these tissues remains unknown. We found that in skin, Lgr6 is not only expressed in the central isthmus, directly above the hair follicle bulge cells as reported previously, but also in the interfollicular epidermis. Lgr6 expression in skin is highly correlated with the innervation sites of cutaneous nerves. In the hair follicle, Lgr6 closely localizes with the surrounding nerve endings and their corresponding Schwann cells throughout the entire hair cycle. Furthermore, ablation of cutaneous nerves leads to degeneration of Schwann cells and diminished expression of Lgr6. Our results demonstrate that the nerve endings/Schwann cells control Lgr6 expression in skin, implying that they play a role in regulation of skin epithelial cells.

Liao, Xin-Hua; Nguyen, Hoang

2014-01-01

88

Nerve communication model by bio-cells and optical dipole coupling effects.  

Science.gov (United States)

A novel design of nerve communications and networks using the coupling effects between bio-cells and optical dipoles is proposed. The electrical signals are coupled to the dipoles and cells which propagate within the optical networks for long distance without any electromagnetic interference. Results have shown that the use of optical spins in the spin networks, referred as Spinnet, can be formed. This technique can be used to improve the nerve communication performance. It is fabricated as a nano-biotic circuit system, and has great potential for future disability applications and diagnosis of the links of nerves across the dead cells. PMID:23305176

Zainol, Farrah Dilla; Thammawongsa, Nopparat; Mitatha, Somsak; Ali, Jalil; Yupapin, Preecha

2013-12-01

89

Role of N-cadherin in Schwann cell precursors of growing nerves.  

Science.gov (United States)

In the present paper, we determine the localization and developmental regulation of N-cadherin in embryonic rat nerves and examine the role of N-cadherin in this system. We also identify a major transition in the architecture of embryonic nerves and relating it to N-cadherin expression. We find that in early embryonic nerves, N-cadherin is primarily expressed in Schwann cell precursors. Pronounced expression is seen at distal nerve fronts where these cells associate with growth cones, and the proximal nerve ends, in boundary cap cells. Unexpectedly, N-cadherin is downregulated as precursors generate Schwann cells, coinciding with the time at which most axons make target connections. Therefore, glial N-cadherin expression is essentially restricted to the period of axon outgrowth. We also provide evidence that N-cadherin supports the formation of contacts between Schwann cell precursors and show that these cells are a favorable substrate for axon growth, unlike N-cadherin-negative Schwann cells. Induction of N-cadherin expression in Schwann cells by neuregulin-1 restores their ability to form contacts and support axon growth. Finally, we show that the loss of glial N-cadherin during embryonic nerve development is accompanied by a transformation of nerve architecture, involving the appearance of endoneurial connective tissue space, fibroblasts, Schwann cell basal lamina, and blood vessels. Because N-cadherin is likely to promote the extensive glial contacts typical of the compact embryonic nerve, we suggest that N-cadherin loss at the time of Schwann cell generation allows endoneurial space to appear between the glial cells, a development that eventually permits the extensive interactions between connective tissue and individual axon-Schwann cell units necessary for myelination. PMID:16886205

Wanner, Ina B; Guerra, Nicole K; Mahoney, James; Kumar, Aman; Wood, Patrick M; Mirsky, Rhona; Jessen, Kristján R

2006-10-01

90

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

Science.gov (United States)

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

Anderson, A J; Harvey, A L

1988-01-01

91

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

LENUS (Irish Health Repository)

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

Henry, F P

2012-06-01

92

Accumulation of nerve growth factor in cerebrospinal fluid and biological activity following neurosurgery.  

Science.gov (United States)

Perioperative nerve growth factor (NGF) levels in cerebrospinal fluid (CSF) of patients with acoustic neurinoma (14 cases), tentorial meningioma (1 case), or subarachnoid hemorrhage (1 case) were examined. Preoperative NGF levels in CSF were below the level of detection in all patients. However, NGF was found to accumulate transiently in CSF following neurosurgery. Pre- and postoperative CSF obtained from a patient with acoustic neurinoma enhanced the proliferation of astrocytes in neuronal cell cultures derived from embryonic rat cortex grown in serum-free defined medium, and increased choline acetyltransferase activity of cholinergic neurons derived from embryonic rat septal area and brainstem. The effect of postoperative CSF on septal and brainstem neurons was more potent than that of preoperative CSF. These results indicate that NGF and non-NGF-type neurotrophic activities accumulate in the CSF following neurosurgery. These neurotrophic activities are probably important in the regeneration of damaged neural networks in the central nervous system. PMID:7477685

Sagoh, M; Yoshida, K; Wakamoto, H; Kamiguchi, H; Otani, M; Shiobara, R; Toya, S

1995-07-01

93

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

Directory of Open Access Journals (Sweden)

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

Sakamoto Atsuhiro

2011-01-01

94

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

2013-01-01

95

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

96

Ionic responses and growth stimulation induced by nerve growth factor and epidermal growth factor in rat pheochromocytoma (PC12) cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Rat pheochromocytoma cells (clone PC12) respond to nerve growth factor (NGF) by the acquirement of a phenotype resembling neuronal cells. In an earlier study we showed that NGF causes an increase in Na+,K+ pump activity, as monitored by ouabain-sensitive Rb+ influx. Here we show that addition of epidermal growth factor (EGF) to PC12 cells resulted in a stimulation of Na+,K+ pump activity as well. The increase of Na+,K+ pump activity by NGF or EGF was due to increased Na+ influx. This increase...

1983-01-01

97

If you have an active vagus nerve, cancer stage may no longer be important.  

Science.gov (United States)

The parasympathetic system, and primarily the vagus nerve, informs the brain about multiple signals and returns the body to homeostasis. Recent studies have shown that vagal nerve activity independently predicts prognosis in cancer. Here, we take this one step further and show that when vagal nerve activity is high, cancer stage no longer predicts tumor burden. We examined whether vagal nerve activity, indexed by Heart Rate Variability (HRV), moderated the effects of initial tumor stage on tumor burden at followup. Patients? HRVs were derived from ECGs near diagnosis in colorectal cancer (CRC) and in prostate cancer (PC) patients. Outcomes included the tumor markers carcinoembryonic antigen (CEA) at 12 months for CRC and prostate-specific antigen (PSA) at 6 months for PC. As would be expected, initially advanced tumor stages of CRC or PC predicted higher tumor marker levels at follow-up than did early stages. However, this occurred only in patients with low, not high, vagal activity (HRV). Furthermore, in patients with advanced tumor stage at diagnosis, high HRV predicted lower tumor marker levels than did low HRV, in both cancers. Estimating a cancer patient?s prognosis by determining his tumor stage needs to also consider the vagal nerve activity. This activity is easily measurable, and it determines in which subjects the tumor stage is prognostic. Importantly, higher vagal activity may even protect against the adverse effects of advanced cancer stage. These findings, observed in two distinct cancers, support the hypothesized neuroimmunomodulatory effects of vagal nerve activity on tumors. PMID:25001652

Gidron, Y; De Couck, M; De Greve, J

2014-01-01

98

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

International Nuclear Information System (INIS)

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

1993-12-01

99

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

100

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

1994-06-15

 
 
 
 
101

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

2001-01-01

102

BOLD fMRI activation induced by vagus nerve stimulation in seizure patients  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Design: Blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) was employed to detect areas of the brain activated by vagus nerve stimulation in five patients with documented complex partial seizures.

Liu, W.; Mosier, K.; Kalnin, A.; Marks, D.

2003-01-01

103

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

104

Nerve growth factor enhances expression of neuron-glia cell adhesion molecule in PC12 cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The neuron-glia cell adhesion molecule (Ng-CAM) has been identified in mammalian brain tissue and PC12 pheochromocytoma cells as Mr 200,000 and Mr 230,000 species, respectively. When PC12 cells were treated with nerve growth factor (NGF), the amount of Ng-CAM at the cell surface was increased approximately threefold, whereas the amount of the neural cell adhesion molecule (N-CAM) remained unchanged. An NGF-inducible large external glycoprotein (NILE) has been previously identified by its enha...

1986-01-01

105

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2007-01-01

106

Muscle-Derived Cells (MDCs) for Promoting and Enhancing Nerve Repair and Regeneration.  

Science.gov (United States)

The present invention describes methods involving the use of muscle derived cells (MDCs), preferably obtained from skeletal muscle, to support the innervation and repair of damaged tissues and organs, particularly associated with nerve damage or neuropath...

M. R. Chancellor J. Huard B. Minnery

2004-01-01

107

Activity-independent release of the amyloid ?-peptide from rat brain nerve terminals.  

Science.gov (United States)

Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease. The molecular mechanism underlying this degeneration is not fully elucidated but one key player appears to be the synaptotoxic amyloid ?-peptide (A?). The exact localization of the production of A? and the mechanisms whereby A? is released remain elusive. We have earlier shown that A? can be produced in crude synaptic vesicle fractions and it has been reported that increased synaptic activity results in increased secreted but decreased intracellular A? levels. Therefore, we considered whether A? could be produced in synaptic vesicles and/or released through the same mechanisms as neurotransmitters in synaptic vesicle exocytosis. Small amounts of A? were found to be produced in pure synaptic vesicle preparations. We also studied the release of glutamate and A? from rat cortical nerve terminals (synaptosomes). We found that large amounts of A? were secreted from non-stimulated synaptosomes, from which glutamate was not released. On the contrary, we could not detect any differences in A? release between non-stimulated synaptosomes and synaptosomes stimulated with KCl or 4-aminopyridine, whereas glutamate release was readily inducible in this system. To conclude, our results indicate that the major release mechanism of A? from isolated nerve terminals differs from the synaptic release of glutamate and that the activity-dependent increase of secreted A?, reported by several groups using intact cells, is likely dependent on post-synaptic events, trafficking and/or protein synthesis mechanisms. PMID:24602978

Lundgren, Jolanta L; Ahmed, Saheeb; Winblad, Bengt; Gouras, Gunnar K; Tjernberg, Lars O; Frykman, Susanne

2014-04-30

108

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

International Nuclear Information System (INIS)

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

2002-10-01

109

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

110

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

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

Fregnan, Federica; Geuna, Stefano

2008-01-01

111

Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice  

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Abstract Autophagy is an essential recycling pathway implicated in neurodegeneration either as a pro-survival or a pro-death mechanism. Its role after axonal injury is still uncertain. Axotomy of the optic nerve is a classical model of neurodegeneration. It induces retinal ganglion cell death, a process also occurring in glaucoma and other optic neuropathies. We analyzed autophagy induction and cell survival following optic nerve transection in mice. Our results demonstrate activat...

2011-01-01

112

The use of undifferentiated bone marrow stromal cells for sciatic nerve regeneration in rats.  

Science.gov (United States)

In recent years, cell transplantation has become a focus of attention and reliable outcomes have been achieved in regeneration of the sciatic nerve. The effect of undifferentiated bone marrow stromal cells (BMSCs) on peripheral nerve regeneration was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using an inside-out vein graft (IOVG) filled with undifferentiated BMSCs (2 × 10(7)cells/ml). In the control group, the vein was filled with phosphate buffer saline alone. The regenerated fibres were studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was based on functional (walking track analysis), histomorphometric and immunohistochemical (Schwann cell detection by S100 expression) criteria. The functional study confirmed significant recovery of regenerated axons in the IOVG/BMSC group (P<0.05). Quantitative morphometric analyses of regenerated fibres showed the number and diameter of myelinated fibres in the IOVG/BMSC group were significantly higher than in the control group (P<0.05). This demonstrates the potential for using undifferentiated BMSCs in peripheral nerve regeneration without the limitations of donor-site morbidity associated with isolation of Schwann cells. It also reduces costs because the interval between tissue collection and cell injection is reduced and the laboratory procedures are simpler compared to undifferentiated BMSCs. PMID:22154576

Mohammadi, R; Azizi, S; Delirezh, N; Hobbenaghi, R; Amini, K; Malekkhetabi, P

2012-05-01

113

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

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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 o...

Brambilla Roberta; Dvoriantchikova Galina; Barakat David; Ivanov Dmitry; Bethea John R; Shestopalov Valery I

2012-01-01

114

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

Science.gov (United States)

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. PMID:16487971

Pereira Lopes, Fátima Rosalina; Camargo de Moura Campos, Lenira; Dias Corrêa, José; Balduino, Alex; Lora, Silvano; Langone, Francesco; Borojevic, Radovan; Blanco Martinez, Ana Maria

2006-04-01

115

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

Science.gov (United States)

The goal of the present study was to assess whether in vitro-differentiated N1E-115 cells supported by a collagen membrane would enhance rat sciatic nerve regeneration after a crush injury. To set up an appropriate experimental model for investigating the effects of neural cell transplantation, we have recently described the sequence of functional and morphologic changes occurring after a standardized sciatic nerve crush injury with a nonserrated clamp. Functional recovery was evaluated using the sciatic functional index, the static sciatic index, the extensor postural thrust, the withdrawal reflex latency, and ankle kinematics. In addition, histomorphometric analysis was carried out on regenerated nerve fibers by means of the 2D-disector method. Based on the results of the EPT and of some of the ankle locomotor kinematic parameters analyzed, the hypothesis that N1E-115 cells may enhance nerve regeneration is partially supported although histomorphometry disclosed no significant difference in nerve fiber regeneration between the different experimental groups. Therefore, results suggest that enrichment of equine type III collagen membrane with the N1E-115 cellular system in the rat sciatic nerve crush model may support recovery, at least in terms of motor function. The discrepancy between functional and morphological results also suggests that the combined use of functional and morphological analysis should be recommended for an overall assessment of recovery in nerve regeneration studies. PMID:18623156

Luís, A L; Rodrigues, J M; Geuna, S; Amado, S; Simões, M J; Fregnan, F; Ferreira, A J; Veloso, A P; Armada-da-Silva, P A S; Varejão, A S P; Maurício, A C

2008-01-01

116

Expression of trk in MAH cells lacking the p75 low-affinity nerve growth factor receptor is sufficient to permit nerve growth factor-induced differentiation to postmitotic neurons.  

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We have transfected MAH cells, an immortalized sympathoadrenal progenitor cell line, with a plasmid encoding the 140-kDa Trk protein, a nerve growth factor (NGF) receptor with protein-tyrosine kinase activity. NGF promotes neurite outgrowth and proliferation from such cells, indicating that Trk is sufficient to mediate such responses in the absence of significant levels of the endogenous 75-kDa low-affinity NGF receptor (p75). These initial NGF responses are indistinguishable from those evoke...

Verdi, J. M.; Ip, N.; Yancopoulos, G. D.; Anderson, D. J.

1994-01-01

117

Lamellar cells of sensory receptors and perineural cells of nerve endings of pig skin contain cytokeratins.  

Science.gov (United States)

The lamellar cells of the sensory corpuscles of the pig dermis must be considered to be epithelial cells as they contain cytokeratins. The cytokeratins detected are similar to those found in simple epithelia. Moreover, lamellar cells are embedded in an extracellular matrix reminiscent of the basement membrane of epithelium since it contains laminin and collagen IV. The perineural cells surrounding the nerves of pig dermis present the same features. These results suggest that lamellar cells and perineural cells have the same origin. The nature of the lamellar and perineural cells of the rabbit or human dermis is not as clear since cytokeratins were not detected in those cells. These results, together with recent observations on Merkel cells, may indicate that epithelio-neuronal junctions are a general feature of cutaneous sensory receptors. PMID:2436379

Ortonne, J P; Verrando, P; Pautrat, G; Darmon, M

1987-01-01

118

Selective Electrical Stimulation of the Auditory Nerve Activates a Pathway Specialized for High Temporal Acuity  

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Deaf people who use cochlear implants show surprisingly poor sensitivity to the temporal fine structure of sounds. One possible reason is that conventional cochlear implants cannot activate selectively the auditory-nerve fibers having low characteristic frequencies (CFs), which, in normal hearing, phase lock to stimulus fine structure. Recently, we tested in animals an alternative mode of auditory prosthesis employing penetrating auditory-nerve electrodes that permit frequency-specific excita...

Middlebrooks, John C.; Snyder, Russell L.

2010-01-01

119

Interstitial cells of Cajal in the cynomolgus monkey rectoanal region and their relationship to sympathetic and nitrergic nerves  

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The morphology of interstitial cells of Cajal (ICC) in the circular muscle layer of the cynomolgus monkey internal anal sphincter (IAS) and rectum and their relationship to sympathetic and nitrergic nerves were compared by dual-labeling immunohistochemistry. Contractile studies confirmed that nitrergic nerves participate in neural inhibition in both regions whereas sympathetic nerves serve as excitatory motor nerves only in the IAS. Muscle bundles extended from myenteric to submucosal edge in...

Cobine, C. A.; Hennig, G. W.; Bayguinov, Y. R.; Hatton, W. J.; Ward, S. M.; Keef, K. D.

2010-01-01

120

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

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

2012-01-01

 
 
 
 
121

Regulation of neural cell adhesion molecule expression on cultured mouse Schwann cells by nerve growth factor.  

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Schwann cells from early postnatal mouse sciatic nerve were obtained as a homogenous population and shown by indirect immunofluorescence to express the neural cell adhesion molecules L1, N-CAM and J1 and their common carbohydrate epitope L2/HNK-1. L1 and N-CAM are synthesized in molecular forms that are slightly different from those expressed by small cerebellar neurons or astrocytes. As in astrocytes, the J1 antigen is expressed by Schwann cells in multiple forms generally ranging from 160 t...

Seilheimer, B.; Schachner, M.

1987-01-01

122

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

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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

123

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

2007-11-01

124

Electrospun conducting polymer nanofibers and electrical stimulation of nerve stem cells.  

Science.gov (United States)

Tissue engineering of nerve grafts requires synergistic combination of scaffolds and techniques to promote and direct neurite outgrowth across the lesion for effective nerve regeneration. In this study, we fabricated a composite polymeric scaffold which is conductive in nature by electrospinning and further performed electrical stimulation of nerve stem cells seeded on the electrospun nanofibers. Poly-L-lactide (PLLA) was blended with polyaniline (PANi) at a ratio of 85:15 and electrospun to obtain PLLA/PANi nanofibers with fiber diameters of 195 ± 30 nm. The morphology, chemical and mechanical properties of the electrospun PLLA and PLLA/PANi scaffolds were carried out by scanning electron microscopy (SEM), X-ray photo electron spectroscopy (XPS) and tensile instrument. The electrospun PLLA/PANi fibers showed a conductance of 3 × 10?? S by two-point probe measurement. In vitro electrical stimulation of the nerve stem cells cultured on PLLA/PANi scaffolds applied with an electric field of 100 mV/mm for a period of 60 min resulted in extended neurite outgrowth compared to the cells grown on non-stimulated scaffolds. Our studies further strengthen the implication of electrical stimulation of nerve stem cells on conducting polymeric scaffolds towards neurite elongation that could be effective for nerve tissue regeneration. PMID:21813321

Prabhakaran, Molamma P; Ghasemi-Mobarakeh, Laleh; Jin, Guorui; Ramakrishna, Seeram

2011-11-01

125

Selective recovery of fascicular activity in peripheral nerves  

Science.gov (United States)

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

Wodlinger, B.; Durand, D. M.

2011-10-01

126

Differential activation of nerve fibers with magnetic stimulation in humans  

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

Olree Kenneth S

2006-07-01

127

Liquiritin potentiate neurite outgrowth induced by nerve growth factor in PC12 cells  

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Neurite outgrowth and neuronal differentiation play a crucial role in the development of the nervous system. Understanding of neurotrophins induced neurite outgrowth was important to develop therapeutic strategy for axon regeneration in neurodegenerative diseases as well as after various nerve injuries. It has been reported that extension of neurite and differentiation of sympathetic neuron-like phenotype was modulated by nerve growth factor (NGF) in PC12 cells. In this study, NGF mediated ne...

Chen, Zheng-ai; Wang, Jun-long; Liu, Rui-ting; Ren, Jian-ping; Wen, Li-qing; Chen, Xiao-juan; Bian, Guang-xing

2009-01-01

128

Differential Gene Expression in Motor and Sensory Schwann Cells in the Rat Femoral Nerve  

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Phenotypic differences in Schwann cells (SCs) may help guide axonal regeneration down motor or sensory specific pathways following peripheral nerve injury. The goal of this study was to identify phenotypic markers for SCs harvested from the cutaneous (sensory) and quadriceps (motor) branches of the rat femoral nerve and to study the effects of expansion culture on the expression patterns of these motor or sensory phenotypic markers. RNA was extracted from SCs harvested from the motor and sens...

Jesuraj, Nithya J.; Nguyen, Peter K.; Wood, Matthew D.; Moore, Amy M.; Borschel, Gregory H.; Mackinnon, Susan E.; Sakiyama-elbert, Shelly E.

2012-01-01

129

Schwann cell mitochondrial metabolism supports long-term axonal survival and peripheral nerve function  

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Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produc...

2011-01-01

130

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

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

2011-01-01

131

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

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

1999-01-01

132

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

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

1999-01-01

133

Sciatic nerve regeneration by microporous nerve conduits seeded with glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor gene transfected neural stem cells.  

Science.gov (United States)

Neurotrophic factors such as the glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) promote nerve cell survival and regeneration, but their efficacy in repairing a longer gap defect of rat sciatic nerve (15 mm) has not been established. In this study, two recombinant mammalian vectors containing either rat GDNF gene or BDNF gene were constructed and each was transfected into neural stem cells (NSCs). It was found that the transfection of GDNF or BDNF gene into NSCs led to significantly enhanced expression of GDNF or BDNF mRNA. The amount of GDNF or BDNF protein secreted from the transfected NSCs showed a 3.3-fold or 2.5-fold increase than that from nontransfected NSCs, respectively. The regeneration capacity of rat sciatic nerve in a poly(D,L-lactide) conduit seeded with GDNF or BDNF-transfected NSCs was evaluated by the histology, functional gait, and electrophysiology after 8 weeks of implantation. It was observed that the degree of myelination and the size of regenerated tissue in the conduits seeded with GDNF- and BDNF-transfected NSCs were higher than those seeded with the nontransfected NSCs. Conduits seeded with GDNF-transfected NSCs had the greatest number of blood vessels. The functional recovery assessed by the functional gait and electrophysiology was significantly improved for conduits seeded with GDNF or BDNF-transfected NSCs. It was concluded that the genetically modified NSCs may have potential applications in promoting nerve regeneration and functional recovery. PMID:21314831

Fu, Keng-Yen; Dai, Lien-Guo; Chiu, Ing-Ming; Chen, Jeng-Rung; Hsu, Shan-hui

2011-04-01

134

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

Science.gov (United States)

Peripheral nerve injuries and neuropathies lead to profound functional deficits. Here, we have demonstrated that muscle-derived stem/progenitor cells (MDSPCs) isolated from adult human skeletal muscle (hMDSPCs) can adopt neuronal and glial phenotypes in vitro and ameliorate a critical-sized sciatic nerve injury and its associated defects in a murine model. Transplanted hMDSPCs surrounded the axonal growth cone, while hMDSPCs infiltrating the regenerating nerve differentiated into myelinating Schwann cells. Engraftment of hMDSPCs into the area of the damaged nerve promoted axonal regeneration, which led to functional recovery as measured by sustained gait improvement. Furthermore, no adverse effects were observed in these animals up to 18 months after transplantation. Following hMDSPC therapy, gastrocnemius muscles from mice exhibited substantially less muscle atrophy, an increase in muscle mass after denervation, and reorganization of motor endplates at the postsynaptic sites compared with those from PBS-treated mice. Evaluation of nerve defects in animals transplanted with vehicle-only or myoblast-like cells did not reveal histological or functional recovery. These data demonstrate the efficacy of hMDSPC-based therapy for peripheral nerve injury and suggest that hMDSPC transplantation has potential to be translated for use in human neuropathies. PMID:24642464

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

2014-04-01

135

Effect of genetically modified Schwann cells with increased motility in end-to-side nerve grafting.  

Science.gov (United States)

Taking into account that Schwann-cell (SC) motility is a prerequisite for myelination during peripheral nerve regeneration, the present study was designed with the intention to increase SC motility in vitro and to evaluate the effect of transduced SC on nerve regeneration in vivo, through silicone tubes after end-to-side nerve repair. Our in vitro study demonstrated that SC transduction with the pREV-HW3 retrovirus, encoding for sialyl-transferase-X (STX), significantly increased their motility compared to the control. In the in vivo study, 45 Wistar rats were randomized into three groups of 15 each. In all animals, the left peroneal nerve was severed, and a 10-mm segment was removed. The distal stump of the peroneal nerve was connected end-to-side to a perineurial window in the ipsilateral tibial nerve with either a silicone tube lined with SC (group A) or a silicone tube lined with STX-transduced SC (groups B and C). Fluorescence and light microscopy in group C showed that SCs were viable the first critical 15 postoperative days. After 90 days, light microscopy in group B demonstrated that STX-transduced SCs with increased motility ensured nerve regeneration, through silicone tubes, in all cases. Furthermore, STX-transduced SCs increased significantly fiber diameter and myelin thickness, and most importantly enhanced significantly the functional outcome compared to non-transduced SCs. PMID:16032724

Gravvanis, Andreas I; Lavdas, Alexandros; Papalois, Apostolos E; Franceschini, Isabelle; Tsoutsos, Dimosthenis A; Dubois-Dalcq, Monique; Matsas, Rebecca; Ioannovich, John D

2005-01-01

136

Regulation of neural cell adhesion molecule expression on cultured mouse Schwann cells by nerve growth factor.  

Science.gov (United States)

Schwann cells from early postnatal mouse sciatic nerve were obtained as a homogenous population and shown by indirect immunofluorescence to express the neural cell adhesion molecules L1, N-CAM and J1 and their common carbohydrate epitope L2/HNK-1. L1 and N-CAM are synthesized in molecular forms that are slightly different from those expressed by small cerebellar neurons or astrocytes. As in astrocytes, the J1 antigen is expressed by Schwann cells in multiple forms generally ranging from 160 to 230 kd in the reduced state. J1 is secreted by Schwann cells in a 230-kd mol. wt form. Expression of L1 by Schwann cells can be regulated by nerve growth factor (NGF). L1 expression on the cell surface is increased 1.6-fold in the presence of NGF after 3 days of maintenance in vitro and 3-fold after 16 days. NGF does not change expression of N-CAM. The glia-derived neurite-promoting factor (GdNPF) increases L1 expression by a factor of 1.9 and decreases N-CAM expression by a factor of 0.4 after 3 days in vitro. J1 expression on Schwann cell surfaces remains unchanged in the presence of NGF or GdNPF. Antibodies to NGF abolish the influence of NGF on L1 expression. Addition of NGF antibodies to the Schwann cell cultures without exogenously added NGF decreases L1 expression, indicating that Schwann cells secrete NGF that may influence L1 expression by an autocrine mechanism. Our experiments show for the first time that cell adhesion molecule expression on a non-neuronal cell, the Schwann cell, can be directly regulated by the neurotrophic factor NGF. These observations indicate a considerable degree of 'plasticity' of peripheral glia in regulating cell adhesion molecule expression. PMID:3608988

Seilheimer, B; Schachner, M

1987-06-01

137

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

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

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

2012-01-01

138

Effect of contraction intensity on sympathetic nerve activity to active human skeletal muscle  

Science.gov (United States)

The effect of contraction intensity on muscle sympathetic nerve activity (MSNA) to active human limbs has not been established. To address this, MSNA was recorded from the left peroneal nerve during and after dorsiflexion contractions sustained for 2 min by the left leg at ~10, 25, and 40% MVC. To explore the involvement of the muscle metaboreflex, limb ischemia was imposed midway during three additional contractions and maintained during recovery. Compared with total MSNA at rest (11.5 ± 4.1 mv.min?1), MSNA in the active leg increased significantly at the low (21.9 ± 13.6 mv.min?1), medium (30.5 ± 20.8 mv.min?1), and high (50.0 ± 24.5 mv.min?1) intensities. This intensity-dependent effect was more strongly associated with increases in MSNA burst amplitude than burst frequency. Total MSNA then returned to resting levels within the first minute of recovery. Limb ischemia had no significant influence on the intensity-dependent rise in MSNA or its decline during recovery in the active leg. These findings reveal intensity-dependent increases in total MSNA and burst amplitude to contracting human skeletal muscle that do not appear to involve the muscle metaboreflex.

Boulton, Daniel; Taylor, Chloe E.; Macefield, Vaughan G.; Green, Simon

2014-01-01

139

Mesenchymal stem cell differentiation to neuronal cells on electrospun nanofibrous substrates for nerve tissue engineering.  

Science.gov (United States)

Bone marrow Mesenchymal stem cells capable of differentiating into neuronal cells on engineered nanofibrous scaffolds have great potential for bionanomaterial-cell transplantation therapy of neurodegenerative diseases and injuries of the nervous system. MSCs have been the highlight of many tissue engineering studies mainly because of their multipotential properties. We investigated the potential of human bone marrow derived Mesenchymal stem cells (MSCs) for neuronal differentiation in vitro on poly(L-lactic acid)-co-poly-(3-caprolactone)/Collagen (PLCL/Coll) nanofibrous scaffolds. PLCL and PLCL/Coll nanofibrous scaffolds were fabricated by electrospinning process and their chemical and mechanical characterizations were carried out using SEM, contact angle, FTIR, and tensile instrument. The differentiation of MSCs was carried out using neuronal inducing factors including beta-mercaptoethanol, epidermal growth factor, nerve growth factor and brain derived growth factor in DMEM/F12 media. The proliferations of MSCs evaluated by MTS assay showed that the cells grown on PLCL/Coll nanofibrous scaffolds were comparatively higher (80%) than those on PLCL. Scanning electron microscopy results showed that MSCs differentiated on PLCL/Coll nanofibrous scaffolds showed neuronal morphology, with multipolar elongations and expressed neurofilament and nestin protein by immuno-fluorescent microscopy. Our studies on the differentiation of MSCs to neuronal cells on nanofibrous scaffolds suggest their potential application towards nerve regeneration. PMID:19539369

Prabhakaran, Molamma P; Venugopal, Jayarama Reddy; Ramakrishna, Seeram

2009-10-01

140

A Schwann cell-seeded intrinsic framework and its satisfactory biocompatibility for a bioartificial nerve graft.  

Science.gov (United States)

To optimize the internal environment of a collagen nerve tube, we designed a Schwann cell-seeded intrinsic framework and its biocompatibility was investigated. We fixed 6-0 polyglactin woven filaments (Vicryl) or polydioxanone monofilaments (PDS) on a silicone ring in a net fashion. It was coated with matrigel and then incubated with cultured newborn or adult Schwann cells. Furthermore, we implanted 1.5-cm-long filament-filled collagen tubes in a rat model. Using a live/dead fluorescent assay and electron microscopy, we found that adherent Schwann cells onto filaments remained viable and oriented longitudinally along filaments. The preliminary in vivo study indicated that a mild inflammatory reaction was present around the tube wall. However, nerve regeneration occurred around and between filaments. We concluded that the arrangement of Schwann cell columns onto filaments was achieved, mimicking Bünger bands. It was shown that the biomaterials did not impede nerve regeneration. PMID:11426639

Shen, Z L; Berger, A; Hierner, R; Allmeling, C; Ungewickell, E; Walter, G F

2001-01-01

 
 
 
 
141

Phylogenetically conserved antigen on nerve cells and lymphocytes resembles myelin-associated glycoprotein.  

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The HNK-1 (Leu 7) and NC-1 monoclonal antibodies, raised against a human T-cell line and against nerve cells of quail embryos, respectively, have been shown to bind to a shared epitope present on the surface of human large granular lymphocytes and on nerve cells in species ranging from amphibians to humans. We demonstrate that a related antigen is also expressed on the lymphocyte surface in the avian central lymphoid organs, thymus and bursa, and in the spleen during embryonic and adult life....

Peault, B.; Chen, C. L.; Cooper, M. D.; Barbu, M.; Lipinski, M.; Le Douarin, N. M.

1987-01-01

142

Laser-activated solder weld repair of the inferior alveolar nerve in rats  

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A new laser activated solder weld technique is described for the microsurgical repair of the inferior alveolar nerve in rats. The laser weld technique used an albumin based solder, containing indocyanine cardiogreen, plus an infrared diode laser. Seven animals had inferior alveolar nerve repairs performed using the laser weld technique and these were compared against corresponding unoperated controls plus three cases of nerve section without repair. Histochemical analysis was performed utilizing neuron counts and horseradish peroxidase tracer (HRP) uptake in the trigeminal ganglion following sacrifice and staining of frozen sections with cresyl violet and diaminobenzidene. The results of this analysis showed comparable mean neuron counts and mean HRP uptake by neurons for the unoperated control and laser weld groups with considerable reduction of mean values in cases of nerve section with no repair. Sections of the repaired inferior alveolar nerves, stained with Masson's trichrome, showed no adverse reactions by axons or epineurium to the coagulative repair with the solder and demonstrated regeneration of myelinated axons at the time of sacrifice. In summary a new technique of laser weld repair of the inferior alveolar nerve is described which, on initial analysis, appears to be a reliable alternative to traditional techniques.

Curtis, Nigel J.; Lauto, Antonio; Trickett, Rodney I.; Owen, Earl; Walker, D. M.

1997-05-01

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

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

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

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

2014-02-01

145

Role of acetylcholine in regulation of interaction between axon and Schwann cell during rhythmic excitation of nerve fibers.  

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Axon excitation increases the number of acetylcholine receptors (ACR) of the Schwann cell (SC) depending on the frequency of rhythmic excitation (RE) and on intercellular concentrations of K+, Ca2+, and acetylcholine. During RE, activity of axonal acetylcholine esterase is decreased, thus providing for high intercellular acetylcholine concentration. Increased intercellular concentration of acetylcholine activates phosphoinositide-specific phospholipase C (PIPLC) of the myelin nerve fiber. During RE, K+ depolarization and acetylcholine exocytosis can activate Ca2+ entry via Ca2+ channels, thus inducing SC ACR phosphorylation mediated by PIPLC stimulation. PMID:10810179

Maximov, G V; Revin, V V; Grunyushkin, I P; Kols, O R

2000-04-01

146

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.

Evan B. Stubbs

2013-02-01

147

Heterogeneous distribution of taste cells in facial and vagal nerve-innervated taste buds.  

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Input from the three gustatory nerves of vertebrates is used to evaluate the nutritional quality of food. In some species, these cranial nerves are modified to accomplish additional specific functions. For example, the facial nerve innervated taste buds distributed over the body surface of catfish aid food search. Physiological studies indicate that this extra-oral taste pathway is more sensitive to amino acids than either the glossopharyngeal or vagal systems of the oral cavity. The current investigation seeks to determine if differences in taste cell subtypes might contribute to the observed differences in sensitivity. The distributions of five low molecular weight metabolites, L-alanine, L-aspartate, L-glutamate, GABA, taurine and the tripeptide glutathione, were examined in 2118 individual taste cells innervated by either the facial or vagal nerve of the channel catfish, Ictalurus punctatus. The metabolite profiles of these cells were determined immunocytochemically and subjected to a k-means clustering algorithm. Fifteen cell classes with quantitatively different patterns of metabolite co-localization were identified. All but one small class of two cells were found in both facial and vagal nerve-innervated taste buds. Four classes (9% of the total cells) had high, two classes (17%) had intermediate and the remaining nine classes (74%) had low levels of GABA immunoreactivity. While the functional significance of differences in metabolite profile remains to be determined, taste cell classes were not uniformly distributed across vagal and facial nerve innervated taste buds and may provide an anatomical basis for previously reported differences in gustatory sensitivity. PMID:16387446

Eram, M; Michel, W C

2006-01-01

148

Understanding regulation of nerve cell death by mGluRs as a method for development of successful neuroprotective strategies.  

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A common cause of nerve cell death often leading to vascular dementia is ischemic stroke. Attempts to develop clinically effective stroke treatment and prevention strategies based on pharmacological manipulations of a single mechanism have not led to clinical success. Analysis of clinical neuroprotection trials suggests that combination treatments may be more effective. To identify optimal components for such treatment, N-methyl-d-aspartate receptor (NMDAR) activation-induced cell death in organotypic hippocampal preparations was studied as a model of neurodegeneration that occurs in association with stroke or vascular dementia. Pharmacological manipulation of metabotropic glutamate receptors mGluR1 and 5 resulted in significant reduction of nerve cell susceptibility to NMDA-induced injury, suggesting that these receptors may function as physiological regulators of neuronal vulnerability. cDNA microarray analysis of over 1000 brain-related genes performed after the neuroprotective activation of group I metabotropic glutamate receptors (mGluRs) revealed a complex pattern of activation and inactivation of seemingly unrelated genes responsible for regulation of neuronal excitability, inflammation, cell death pathways, cell adhesion and transcriptional activation. Combined pharmacological targeting of these processes may provide basis for clinical trials of effective neuroprotective compounds. PMID:15760640

Baskys, Andrius; Blaabjerg, Morten

2005-03-15

149

Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered trigeminal nerve stimulation.  

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Stimulation of the vagus nerve has become an effective method for desynchronizing the highly coherent neural activity typically associated with epileptic seizures. This technique has been used in several animal models of seizures as well as in humans suffering from epilepsy. However, application of this technique has been limited to unilateral stimulation of the vagus nerve, typically delivered according to a fixed duty cycle, independently of whether ongoing seizure activity is present. Here, we report that stimulation of another cranial nerve, the trigeminal nerve, can also cause cortical and thalamic desynchronization, resulting in a reduction of seizure activity in awake rats. Furthermore, we demonstrate that providing this stimulation only when seizure activity begins results in more effective and safer seizure reduction per second of stimulation than with previous methods. Seizure activity induced by intraperitoneal injection of pentylenetetrazole was recorded from microwire electrodes in the thalamus and cortex of awake rats while the infraorbital branch of the trigeminal nerve was stimulated via a chronically implanted nerve cuff electrode. Continuous unilateral stimulation of the trigeminal nerve reduced electrographic seizure activity by up to 78%, and bilateral trigeminal stimulation was even more effective. Using a device that automatically detects seizure activity in real time on the basis of multichannel field potential signals, we demonstrated that seizure-triggered stimulation was more effective than the stimulation protocol involving a fixed duty cycle, in terms of the percent seizure reduction per second of stimulation. In contrast to vagus nerve stimulation studies, no substantial cardiovascular side effects were observed by unilateral or bilateral stimulation of the trigeminal nerve. These findings suggest that trigeminal nerve stimulation is safe in awake rats and should be evaluated as a therapy for human seizures. Furthermore, the results demonstrate that seizure-triggered trigeminal nerve stimulation is technically feasible and could be further developed, in conjunction with real-time seizure-predicting paradigms, to prevent seizures and reduce exposure to nerve stimulation. PMID:11050139

Fanselow, E E; Reid, A P; Nicolelis, M A

2000-11-01

150

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

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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 ove...

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

2008-01-01

151

Nitric Oxide Signaling and Neural Stem Cell Differentiation in Peripheral Nerve Regeneration  

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Objective: The objective was to examine whether nitric oxide signaling plays a role in human embryonic stem cell differentiation into neural cells. This article reviews current literature on nitric oxide signaling and neural stem cell differentiation for potential therapeutic application to peripheral nerve regeneration. Methods: Human embryonic H9-stem cells were grown, maintained on mitomycin C–treated mouse embryonic fibroblast feeder layer, cultured on Matrigel to be feeder-free, and us...

2010-01-01

152

Diffuse large B-cell lymphoma of the nasal cavity presenting as abducens nerve palsy.  

Science.gov (United States)

An 87-year-old man presented with a 1-week history of transient facial numbness, followed by the onset of left diplopia 1 month later. In the neurological examination, he was found to have left abducens nerve palsy. A brain MRI showed an infiltrative lesion invading the left posterior nasal cavity and pterygopalatine fossa, and extending into the left paracavernous region. The histological diagnosis was diffuse large B-cell lymphoma. We report an unusual case of diffuse large B-cell lymphoma occurring in the sinonasal tract with unilateral abducens nerve palsy presenting as an early feature. PMID:24220442

Kang, Ju Wan; Kim, Jeong Hong

2013-11-01

153

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

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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 w...

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

2006-01-01

154

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.)

2007-12-01

155

Quantitative studies of rat carotid body type I cell nerve endings.  

Science.gov (United States)

The results of a stereological and morphometric analysis of rat carotid body type I cell nerve endings are described. 66.9% of endings possessed symmetrical junctions. Of the remaining endings, 3.6% were presynaptic and 26% were postsynaptic to type I cells; 3.6% of endings had a reciprocal configuration. Apart from membrane specialisations, no other ultrastructural criteria were found to distinguish the different types of endings. Ventilation with 100% and 10% oxygen showed that the hypoxic mixture reduced synaptic vesicle concentration in the nerve endings; this effect was independent of the innervation to the carotid body. PMID:3766102

Pallot, D J; Blakeman, N

1986-01-01

156

Fibrin conduit supplemented with human mesenchymal stem cells and immunosuppressive treatment enhances regeneration after peripheral nerve injury.  

Science.gov (United States)

To address the need for the development of bioengineered replacement of a nerve graft, a novel two component fibrin glue conduit was combined with human mesenchymal stem cells (MSC) and immunosupressive treatment with cyclosporine A. The effects of MSC on axonal regeneration in the conduit and reaction of activated macrophages were investigated using sciatic nerve injury model. A 10mm gap in the sciatic nerve of a rat was created and repaired either with fibrin glue conduit containing diluted fibrin matrix or fibrin glue conduit containing fibrin matrix with MSC at concentration of 80×10(6) cells/ml. Cells were labeled with PKH26 prior to transplantation. The animals received daily injections of cyclosporine A. After 3 weeks the distance of regeneration and area occupied by regenerating axons and ED1 positives macrophages was measured. MSC survived in the conduit and enhanced axonal regeneration only when transplantation was combined with cyclosporine A treatment. Moreover, addition of cyclosporine A to the conduits with transplanted MSC significantly reduced the ED1 macrophage reaction. PMID:22465323

McGrath, Aleksandra M; Brohlin, Maria; Kingham, Paul J; Novikov, Lev N; Wiberg, Mikael; Novikova, Liudmila N

2012-05-16

157

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

Science.gov (United States)

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

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

2014-02-01

158

The role of laminin, a component of Schwann cell basal lamina, in rat sciatic nerve regeneration within antiserum-treated nerve grafts.  

Science.gov (United States)

Regeneration of the sciatic nerve in transplanted nerve grafts in which laminin was inactivated was examined electron microscopically. Nerve grafts for transplantation were obtained from close cloned donor Wistar rats; 1-cm nerve segments of the sciatic nerve were frozen and thawed to kill the Schwann cells. Control recipient rats received grafts treated with normal rabbit serum to repair the artificially-made complete defect of the right sciatic nerve, and the experimental group of rats received grafts doubly treated with normal serum and rabbit anti-laminin antiserum. In the control grafts regenerating axons grew almost completely through the inside of the basal lamina scaffolds (92%) and adhered to the structure, while in the anti-laminin antiserum treated grafts the axons were present outside (52%) and inside (48%) the scaffolds simultaneously. In this case, the adhesion of axons to the scaffolds was obscure. Axons were associated with and without Schwann cells both inside and outside the basal lamina scaffolds. No unassociated Schwann cells were observed. The maximal number of axons in a 2 mm portion of the antiserum-treated grafts was approximately 250 axons per 100 x 100 microns square and 520 in the control at 15 days. At 30 days, almost the same number of axons was found at the distal (8 mm) portion of both groups. The growth in the former was delayed for 3 days. These results indicate that regenerating peripheral nerve axons may enter the basal lamina scaffolds and grow well because of the neurotrophic function of laminin present at the inner side of Schwann cell basal lamina. PMID:1617403

Wang, G Y; Hirai, K; Shimada, H

1992-01-20

159

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

Science.gov (United States)

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

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

2013-03-29

160

Goldfish brain extract induces aggregation of acetylcholine receptors on cultured myotubes: increased activity following optic nerve axotomy.  

Science.gov (United States)

Acetylcholine receptor aggregation-inducing factor(s) is found in goldfish brain extract. The specific activity of the factor(s) is increased during goldfish optic nerve regeneration and peaks at 8 days following the nerve axotomy. It is therefore speculated that this activity is associated with the goldfish visual system plasticity. PMID:7322451

Schwartz, M; Vogel, Z; Kalcheim, C

1981-12-11

 
 
 
 
161

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

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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, dendriti...

Lambrecht Bart N

2001-01-01

162

Active calcium responses recorded optically from nerve terminals of the frog neurohypophysis  

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Voltage-sensitive dyes were used to record by optical means membrane potential changes from nerve terminals in the isolated frog neurohypophysis. Following the block of voltage-sensitive Na+ channels by tetrodotoxin (TTX) and K+ channels by tetraethylammonium (TEA), direct electric field stimulation of the nerve terminals still evoked large active responses. These responses were reversibly blocked by the addition of 0.5 mM CdCl2. At both normal and low [Na+]o, the regenerative response appear...

1985-01-01

163

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

164

[An analysis of mediator secretion in the active zone of the motor nerve ending].  

Science.gov (United States)

The topography of transmitter release sites at the motor-nerve terminal of the cutaneous-pectoris frog muscle has been determined using three extracellular electrodes. It is shown that release sites are united in groups arranged transversally to the nerve endings and reflecting the transmitter release in the active zones (AZ) of the nerve terminal. The quantitative analysis of revealed groups has permitted concluding that the maximal level of secretion is at the centre of AZ, decreasing to the edge and aside from AZ. At the low extracellular Ca2+ concentration all the AZ take part in the spontaneous release process, while in the evoked one--only some of AZ. Advantages of the three-microelectrode method over the two-microelectrode one are analyzed. It is found that the transmitter secretion in spatially isolated AZ leads to the polymodality in uniquantal signal amplitude distribution at extracellular recording. The role of AZ in the transmitter release process is discussed. PMID:1975947

Zefirov, A L; Benish, T V; Fatkullin, N F; Cheranov, S Iu

1990-01-01

165

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

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

Al-Jashamy Karim

2011-01-01

166

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

Science.gov (United States)

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

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

1996-01-01

167

Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair  

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In future, adipose-derived stem cells (ASC) might be used to treat neurological disorders. In this study, the neurotrophic and angiogenic properties of human ASC were evaluated, and their effects in a peripheral nerve injury model were determined. In vitro growth factor stimulation of the cells resulted in increased secretion of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor-A (VEGF-A), and angiopoietin-1 proteins. C...

Kingham, Paul J.; Kolar, Mallappa K.; Novikova, Liudmila N.; Novikov, Lev N.; Wiberg, Mikael

2013-01-01

168

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

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

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

2012-01-01

169

Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves.  

Science.gov (United States)

A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK1)] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK1 receptor knockout (NK1-/-) mice. We now report that, in the complete absence of NK1 receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, number, and contact with nerve elements. For this purpose, mast cell-deficient Kit(W)/Kit(W-v) mice were reconstituted with wild-type or NK1-/- bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK1 receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK1 receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of Kit(W)/Kit(W-v) mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms. PMID:15458971

D'Andrea, Michael R; Saban, Marcia R; Gerard, Norma P; Wershil, Barry K; Saban, Ricardo

2005-02-01

170

Dimorphic myelin in the rat optic nerve as a result of retinal activity blockage by tetrodotoxin during early postnatal period  

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The effects of the retinal ganglion cell (RGC) activity blockage on the early myelination of the rat optic nerve (ON) were investigated at the light and ultrastructural levels. The blockage of the RGC action potential was attained by the use of tetrodotoxin (PX), a blocker of the voltage-sensitive sodium c h a ~ e i sT.T X was either infused directly into the left eye (TON) or injected systematically (SON). These two groups of ONs were compared with the untreat...

Crespo, D.; Verduga, R.; Villegas, J.; Ferna?ndez-viadero, C.

1995-01-01

171

Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors  

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Thyroid hormone (3,5,3?-triiodo-l-thyronine or T3) exerts a pleiotropic activity during central nervous system development. Hypothyroidism during the fetal and postnatal life results in an irreversible mental retardation syndrome. At the cellular level, T3 is known to act on neuronal and glial lineages and to control cell proliferation, apoptosis, migration, and differentiation. Oligodendrocyte precursor cells (OPC) found at birth in the optic nerves are self-renewing cells that normally di...

2002-01-01

172

Human Tryptase Cleaves Pro-Nerve Growth Factor (Pro-NGF): HINTS OF LOCAL, MAST CELL-DEPENDENT REGULATION OF NGF/PRO-NGF ACTION*  

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Several factors regulate nerve growth factor (NGF), which is formed from pro-NGF by intracellular and extracellular enzymatic cleavage. The close proximity between mast cells expressing the protease tryptase and NGF-producing smooth muscle-like peritubular cells in the testes of infertile patients led us to examine whether tryptase is among those factors. Human peritubular cells express functional tryptase receptors (PAR-2). Recombinant enzymatically active ?-tryptase increased NGF levels in...

Spinnler, Katrin; Fro?hlich, Thomas; Arnold, Georg J.; Kunz, Lars; Mayerhofer, Artur

2011-01-01

173

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

Science.gov (United States)

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

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

2013-04-01

174

Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma  

Science.gov (United States)

Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wlds allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.

Howell, Gareth R.; Libby, Richard T.; Jakobs, Tatjana C.; Smith, Richard S.; Phalan, F. Campbell; Barter, Joseph W.; Barbay, Jessica M.; Marchant, Jeffrey K.; Mahesh, Nagaraju; Porciatti, Vittorio; Whitmore, Alan V.; Masland, Richard H.; John, Simon W. M.

2007-01-01

175

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

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

Ribeiro M.M.

2001-01-01

176

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

Scientific Electronic Library Online (English)

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

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

177

Ocular hypertension impairs optic nerve axonal transport leading to progressive retinal ganglion cell degeneration.  

Science.gov (United States)

Ocular hypertension (OHT) is the main risk factor of glaucoma, a neuropathy leading to blindness. Here we have investigated the effects of laser photocoagulation (LP)-induced OHT, on the survival and retrograde axonal transport (RAT) of adult rat retinal ganglion cells (RGC) from 1 to 12 wks. Active RAT was examined with fluorogold (FG) applied to both superior colliculi (SCi) 1 wk before processing and passive axonal diffusion with dextran tetramethylrhodamine (DTMR) applied to the optic nerve (ON) 2 d prior to sacrifice. Surviving RGCs were identified with FG applied 1 wk pre-LP or by Brn3a immunodetection. The ON and retinal nerve fiber layer were examined by RT97-neurofibrillar staining. RGCs were counted automatically and color-coded density maps were generated. OHT retinas showed absence of FG+ or DTMR+RGCs in focal, pie-shaped and diffuse regions of the retina which, by two weeks, amounted to, approximately, an 80% of RGC loss without further increase. At this time, there was a discrepancy between the total number of surviving FG-prelabelled RGCs and of DMTR+RGCs, suggesting that a large proportion of RGCs had their RAT impaired. This was further confirmed identifying surviving RGCs by their Brn3a expression. From 3 weeks onwards, there was a close correspondence of DTMR+RGCs and FG+RGCs in the same retinal regions, suggesting axonal constriction at the ON head. Neurofibrillar staining revealed, in ONs, focal degeneration of axonal bundles and, in the retinal areas lacking backlabeled RGCs, aberrant staining of RT97 characteristic of axotomy. LP-induced OHT results in a crush-like injury to ON axons leading to the anterograde and protracted retrograde degeneration of the intraocular axons and RGCs. PMID:19835874

Salinas-Navarro, Manuel; Alarcón-Martínez, Luis; Valiente-Soriano, Francisco J; Jiménez-López, Manuel; Mayor-Torroglosa, Sergio; Avilés-Trigueros, Marcelino; Villegas-Pérez, María Paz; Vidal-Sanz, Manuel

2010-01-01

178

Increased cyclic AMP in in vitro regenerating frog sciatic nerves inhibits Schwann cell proliferation but has no effect on axonal outgrowth.  

Science.gov (United States)

In the present study the role of cAMP for axonal outgrowth and Schwann cell proliferation was studied using the cultured frog sciatic nerve. An intrinsic rise in nerve and ganglionic cAMP could be measured as a response to nerve injury, both in vitro and in vivo. Treatment with 0.1-1.0 microM forskolin, an activator of the cAMP-generating enzyme adenylyl cyclase, increased the cAMP content up to 13-fold, but was yet without effect on axonal outgrowth during an 8-day culturing period. HA-1004, an inhibitor of cAMP-dependent protein kinase, also lacked effect on the regeneration. In contrast, the proliferation of Schwann cells, measured as [3H]thymidine incorporation, was inhibited to about 70% of control by forskolin, whereas HA-1004 stimulated proliferation to approximately 130% of control. The results suggest that cAMP is involved in the injury-induced proliferation of Schwann cells of an adult peripheral nerve but that it lacks a central role in the regeneration of sensory axons of such nerves. PMID:8531226

Ekström, P A

1995-09-01

179

Afferent and efferent nerve activity of arterial baroreceptor reflex under nonpulsatile systemic circulation.  

Science.gov (United States)

We studied the changes in arterial baroreceptor reflex (ABR) afferent activity and efferent activity induced by nonpulsatile systemic circulation (NC) during total left heart bypass (TLHB) in rabbits. To evaluate the influence of the circuit priming fluid and exposure to NC, we directly measured aortic depressor nerve activity (ADNA) (n = 5) and renal sympathetic nerve activity (RSNA) (n = 5) before the start of partial left heart bypass (PLHB) (Before), after PHLB (After), and 5 min after the start of TLHB (During THLB) while maintaining the mean aortic pressure. The circuit priming fluid did not affect the ABR. ADNA exhibited periodic discharge at Before and After, but at During THLB, this periodic discharge transformed into a continuous discharge, and ADNA increased significantly. However, there were no significant differences in RSNA. Our results suggested that in the acute phase under NC, the ABR differed from that under natural circulation. PMID:10392276

Shomura, Y; Tanaka, K; Takabayashi, S; Hioki, I; Tenpaku, H; Maze, Y; Shimono, T; Shimpo, H; Yada, I

1999-06-01

180

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

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

HISAYOSHIMURAI

2012-05-01

 
 
 
 
181

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

Science.gov (United States)

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

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

2013-02-01

182

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

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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

2001-04-01

183

Stichopin-containing nerves and secretory cells specific to connective tissues of the sea cucumber.  

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Stichopin, a 17-amino acid peptide isolated from a sea cucumber, affects the stiffness change of the body-wall catch connective tissues and the contraction of the body-wall muscles. The localization of stichopin in sea cucumbers was studied by indirect immunohistochemistry using antiserum against stichopin. Double staining was performed with both stichopin antiserum and 1E11, the monoclonal antibody specific to echinoderm nerves. A stichopin-like immunoreactivity (stichopin-LI) was exclusively found in the connective tissues of various organs. Many fibres and cells with processes were stained by both the anti-stichopin antibody and 1E11. They were found in the body-wall dermis and the connective tissue layer of the cloacae and were suggested to be connective tissue-specific nerves. Oval cells with stichopin-LI (OCS) without processes were found in the body-wall dermis, the connective tissue sheath of the longitudinal body-wall muscles, the connective tissue layer of the tube feet and tentacles, and the connective tissue in the radial nerves separating the ectoneural part from the hyponeural part. Electron microscopic observations of the OCSs in the radial nerves showed that they were secretory cells. The OCSs were located either near the well-defined neural structures or near the water-filled cavities, such as the epineural sinus and the canals of the tube feet. The location near the water-filled cavities might suggest that stichopin was secreted into these cavities to function as a hormone. PMID:17623636

Tamori, Masaki; Saha, Apurba Kumar; Matsuno, Akira; Noskor, Sukumar Chandra; Koizumi, Osamu; Kobayakawa, Yoshitaka; Nakajima, Yoko; Motokawa, Tatsuo

2007-09-22

184

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

Science.gov (United States)

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

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

2010-07-01

185

Investigation of Schwann cell behaviour on RGD-functionalised bioabsorbable nanocomposite for peripheral nerve regeneration.  

Science.gov (United States)

Current commercially available nerve conduits fail to support nerve regeneration gaps larger than 30 mm in length due to the simple intra-luminal design of these conduits which are unable to biomimic the native neural environment. There is, therefore, a major clinical demand for new smart biomaterials, which can stimulate neuronal cell proliferation and migration, and facilitate nerve regeneration across these critical sized defects. In this study, we aimed to investigate Schwann cell (SC) behaviour seeded on the bioabsorbable version of the nanocomposite material, POSS modified poly (caprolactone) urea urethane (PCL), functionalised with arginine-glycine-aspartic acid (RGD) peptide. Successful synthesis of RGD peptide as well as the chemical structure of POSS-PCL nanocomposite film was investigated by Fourier transform infrared spectroscopy. Cell viability assay and morphological assessment were performed to investigate the cytocompatibility of the fabricated constructs. Successful immobilisation of RGD peptide onto the nanocomposite surface was confirmed by water contact angle, Brilliant Blue (BB) staining and thin layer chromatography. Both POSS-PCL and RGD-POSS-PCL nanocomposite scaffolds supported SC attachment, proliferation and morphological differentiation, important aspects for peripheral nerve regeneration. However, a significant increase in SC process length and morphological differentiation towards maturation was observed on the cells grown on RGD-POSS-PCL film. RGD-POSS-PCL nanocomposite demonstrated a significant improvement in SCs spreading and its integrin-dependent process outgrowth (P<0.05). Conduits made by POSS-nanocomposite may be suitable for the next generation of commercially available conduit required to meet current clinical demand in peripheral nerve regeneration and repair as they are currently undergoing in vivo preclinical study. PMID:24503165

Sedaghati, Tina; Jell, Gavin; Seifalian, Alexander

2014-05-25

186

Post-injury regeneration in rat sciatic nerve facilitated by neurotrophic factors secreted by amniotic fluid mesenchymal stem cells.  

Science.gov (United States)

Amniotic fluid mesenchymal stem cells have the ability to secrete neurotrophic factors that are able to promote neuron survival in vitro. The purpose of this study was to evaluate the effects of neurotrophic factors secreted by rat amniotic fluid mesenchymal stem cells on regeneration of sciatic nerve after crush injury. Fifty Sprague-Dawley rats weighing 250-300 g were used. The left sciatic nerve was crushed with a vessel clamp. Rat amniotic fluid mesenchymal stem cells embedded in fibrin glue were delivered to the injured nerve. Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect neurotrophic factors secreted by the amniotic fluid mesenchymal stem cells. Nerve regeneration was assessed by motor function, electrophysiology, histology, and immunocytochemistry studies. Positive CD29/44, and negative CD11b/45, as well as high levels of expression of brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor, ciliary neurotrophic factor (CNTF), nerve growth factor, and neurotrophin-3 (NT-3) were demonstrated in amniotic fluid mesenchymal stem cells. Motor function recovery, the compound muscle action potential, and nerve conduction latency showed significant improvement in rats treated with amniotic fluid mesenchymal stem cells. ELISA measurement in retrieved nerves displayed statistically significant elevation of CNTF and NT-3. The immunocytochemical studies demonstrated positive staining for NT-3 and CNTF in transplanted cells. The histology and immunocytochemistry studies revealed less fibrosis and a high level of expression of S-100 and glial fibrillary acid protein at the crush site. Rat amniotic fluid mesenchymal stem cells may facilitate regeneration in the sciatic nerve after crush injury. The increased nerve regeneration found in this study may be due to the neurotrophic factors secreted by amniotic fluid mesenchymal stem cells. PMID:17954375

Pan, Hung-Chuan; Cheng, Fu-Chou; Chen, Chun-Jung; Lai, Shu-Zhen; Lee, Chi-Wen; Yang, Dar-Yu; Chang, Ming-Hong; Ho, Shu-Peng

2007-11-01

187

The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells  

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Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP. To elucidate further the role of cAMP in NGF-induced neurite outgrowth we have used the adenylate cyclase activator forskolin, cAMP, and a set of chemically modified cAMP analogues, including the adenosine cyclic 3',5'-phosphorothioates (cAMPS) (Rp)-cAMPS and (Sp)-cAMPS. These diastereomers have differentia...

1986-01-01

188

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

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Abstract Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a ves...

Pan Hung-Chuan; Yang Dar-Yu; Ho Shu-Peng; Sheu Meei-Ling; Chen Chung-Jung; Hwang Shiaw-Min; Chang Ming-Hong; Cheng Fu-Chou

2009-01-01

189

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

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Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals ...

Pan, Hung-chuan; Yang, Dar-yu; Ho, Shu-peng; Sheu, Meei-ling; Chen, Chung-jung; Hwang, Shiaw-min; Chang, Ming-hong; Cheng, Fu-chou

2009-01-01

190

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

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

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

2007-01-01

191

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

2012-01-01

192

Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration  

Science.gov (United States)

This paper describes a novel biodegradable conduit that provides a combination of physical, chemical and biological cues at the cellular level to facilitate peripheral nerve regeneration. The conduit consists of a porous poly(D,L-lactic acid) (PDLLA) tubular support structure with a micropatterned inner lumen. Schwann cells were pre-seeded into the lumen to provide additional trophic support. Conduits with micropatterned inner lumens pre-seeded with Schwann cells (MS) were fabricated and compared with three types of conduits used as controls: M (conduits with micropatterned inner lumens without pre-seeded Schwann cells), NS (conduits without micropatterned inner lumens pre-seeded with Schwann cells) and N (conduits without micropatterned inner lumens, without pre-seeded Schwann cells). The conduits were implanted in rats with 1 cm sciatic nerve transections and the regeneration and functional recovery were compared in the four different cases. The number or size of regenerated axons did not vary significantly among the different conduits. The time of recovery, and the sciatic function index, however, were significantly enhanced using the MS conduits, based on qualitative observations as well as quantitative measurements using walking track analysis. This demonstrates that biodegradable micropatterned conduits pre-seeded with Schwann cells that provide a combination of physical, chemical and biological guidance cues for regenerating axons at the cellular level offer a better alternative for repairing sciatic nerve transactions than conventional biodegradable conduits.

Rutkowski, Gregory E.; Miller, Cheryl A.; Jeftinija, Srdija; Mallapragada, Surya K.

2004-09-01

193

Novel Adult Stem Cells for Peripheral Nerve Regeneration.  

Science.gov (United States)

Adult tissues have amazing regeneration potential. However, the cell sources involved in regeneration have not been clearly identified. Recently, we identified a novel type of multipotent stem cells from blood vessels, termed multipotent vascular stem cel...

S. Li

2012-01-01

194

A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA  

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The topology of signal transduction is particularly important for neurons. Neurotrophic factors such as nerve growth factor (NGF) interact with receptors at distal axons and a signal is transduced by retrograde transport to the cell body to ensure survival of the neuron. We have discovered an organelle that may account for the retrograde transport of the neurotrophin signal. This organelle is derived from endocytosis of the receptor tyrosine kinase for NGF, TrkA. In vitro reactions containing...

Grimes, Mark L.; Beattie, Eric; Mobley, William C.

1997-01-01

195

Nerve growth factor increases the sensitivity to zinc toxicity and induces cell cycle arrest in PC12 cells.  

Science.gov (United States)

Zinc is a basic trace element that plays important roles in brain and, consequently, its homeostasis needs to be critically controlled. High zinc concentrations in the interneuron synaptic space may induce neuronal death through mechanisms still partially solved. Undifferentiated pheochromocytoma (PC12) cells have been used to study zinc toxicity. As these cells can be differentiated into neuronal-like cells, the results obtained from differentiated cultures are more useful to understand zinc toxicity in neurons. In this paper, we show by flow cytometry that nerve growth factor (NGF) induces PC12 cells differentiation characterized by cell cycle arrest in the G1/G0 phase, similarly to that observed in serum-deprived cultures. Zinc induces cell death in NGF-differentiated PC12 cultures with an EC(50) value of 143+/-14 microM, which reveals a higher sensitivity with respect to undifferentiated PC12 cultures (EC(50), 308+/-32 microM) and a similar response to that obtained in hippocampal neurons (134+/-12 microM). Thus, the differentiation process appeared responsible for such increase in sensitivity. To further support this tenet, when the NGF differentiation was impaired in presence of 10 microM MK-801, a selective blocker of the N-methyl-d-aspartate (NMDA) receptor that plays a role in the differentiation process, the higher sensitivity to zinc was reverted to an EC(50) value of 241+/-26 microM. Flow cytometry experiments showed that NGF-differentiated PC12 cells in presence of zinc were positive for propidium iodide but not for annexin-V labeling. These results, together with data from fluorescent labeling of nuclear fragmentation, caspase-3 activation, and reactive oxygen species generation, support the view that zinc toxicity in NGF-differentiated PC12 cells takes place mainly through a necrotic process. PMID:19931600

Sánchez-Martín, Francisco J; Valera, Elvira; Casimiro, Ilda; Merino, Jaime M

2010-03-16

196

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

2013-08-16

197

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

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Interstitial cells of Cajal (ICC) have been shown to participate in nitrergic neurotransmission in various regions of the gastrointestinal (GI) tract. Recently, fibroblast-like cells, which are positive for platelet-derived growth factor receptor ? (PDGFR?+), have been suggested to participate additionally in inhibitory neurotransmission in the GI tract. The distribution of ICC and PDGFR?+ cell populations and their relationship to inhibitory nerves within the mouse internal anal sphincter...

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

2011-01-01

198

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

Directory of Open Access Journals (Sweden)

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

Christine Radtke

2012-10-01

199

Activation of the endocannabinoid system by organophosphorus nerve agents  

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?9-Tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana, exhibits useful medicinal properties, but also undesirable side-effects. The brain receptor for THC, CB1, is also activated by the endogenous cannabinoids anandamide and 2-arachidonylglycerol (2-AG). Augmentation of endocannabinoid signaling by blockade of their metabolism may offer a more selective pharmacological approach compared to CB1 agonists. Consistent with this premise, inhibitors of the anandamide-degrading en...

Nomura, Daniel K.; Blankman, Jacqueline L.; Simon, Gabriel M.; Fujioka, Kazutoshi; Issa, Roger S.; Ward, Anna M.; Cravatt, Benjamin F.; Casida, John E.

2008-01-01

200

Selectivity of Ca2+ channel blockers in inhibiting muscular and nerve activities in isolated colon.  

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1. Potency and efficacy of nifedipine, verapamil and diltiazem and of Bay K 8644 in modifying propulsion and nerve or smooth muscle activities have been compared in the guinea-pig isolated distal colon. Both the neuronal and muscular effects of Ca2+ channel blockers seem to develop at concentrations that are devoid of any significant effect apart from that on Ca2+ channels. 2. Nifedipine, verapamil and diltiazem were all able to impair propulsion, resting and stimulated acetylcholine (ACh) re...

Lecchini, S.; Marcoli, M.; Ponti, F.; Castelletti, C. A.; Frigo, G. M.

1991-01-01

 
 
 
 
201

Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.  

Science.gov (United States)

To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature. PMID:9950935

DiBona, G F; Sawin, L L

1999-02-01

202

Effect of pimobendan on cardiopulmonary baroreflex control of sympathetic nerve activity in healthy young men.  

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In order to determine the effect of pimobendan on sympathetic nerve activity and cardiopulmonary baroreflex (CPB), electrocardiogram, direct arterial pressure, central venous pressure (CVP) and cardiac output were recorded along with muscle sympathetic nerve activity (MSNA) in 8 healthy young men. CPB function was evaluated before and 60 min after oral administration of 5 mg pimobendan using the response of MSNA to lower body negative pressure (LBNP) of -5 and -10 mm Hg. The same protocol also was performed during handgrip exercise. Cardiac index, MSNA increased and CVP decreased significantly (ppimobendan administration. During LBNP, CVP decreased and MSNA increased significantly. CPB sensitivity was augmented from 5.53+/-0.75 to 8.59+/-0.78 burst incidence/mm Hg after pimobendan administration (pPimobendan did not alter the percentage increase of MSNA during handgrip exercise. In conclusion, pimobendan induces an increase in basal sympathetic nerve activity by decreasing CVP and augmenting CPB sensitivity without changing arterial pressure in healthy young men. PMID:16199209

Maruyama, Michiro; Takamura, Masayuki; Takata, Shigeo; Murai, Hisayoshi; Usui, Soichiro; Furusho, Hiroshi; Sakagami, Satoru; Yuasa, Toyoshi; Shimakura, Atsuhiro; Kaneko, Shuichi

2005-10-30

203

PACAP-38 activates parasympathetic nerves in isolated, blood-perfused dog atria.  

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A pituitary adenylate cyclase-activating polypeptide (PACAP) activates PACAP and vasoactive intestinal peptide (VIP) receptors. We investigated the effects of PACAP-38 on the sinus rate and atrial contractile force in isolated, blood-perfused dog heart preparations and the stimulation by PACAP-38 of the parasympathetic nerve fibers. PACAP-38 (3-1000 pmol) caused positive and/or negative chronotropic responses and it dose dependently increased atrial and ventricular contractile force. The positive cardiac responses to PACAP-38 unlike those to VIP were much less than the positive responses to norepinephrine. Atropine inhibited the negative chronotropic responses to PACAP-38 and augmented the positive chronotropic and inotropic responses. Physostigmine potentiated the negative cardiac responses to PACAP-38 and acetylcholine. After physostigmine treatment, additionally, tetrodotoxin blocked the negative cardiac responses to PACAP-38 and intracardiac parasympathetic nerve stimulation. Propranolol did not inhibit the positive cardiac responses to PACAP-38 in atropine-treated atria. PACAP-(6-38) (1 and 3 nmol), an antagonist of PACAP-38, did not affect the cardiac responses to 100 pmol of PACAP-38. These results suggest that (1) PACAP-38 directly increases sinus rate and atrial contractile force and (2) PACAP-38 activates parasympathetic nerves and causes negative chronotropic and inotropic responses in the dog heart. PMID:8982667

Yonezawa, T; Furukawa, Y; Lakhe, M; Nagashima, Y; Hirose, M; Chiba, S

1996-11-21

204

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

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

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

2010-01-01

205

In vivo introduction of transgenes into mouse sciatic nerve cells in situ using viral vectors.  

Science.gov (United States)

The myelin sheath is essential for the rapid and efficient propagation of action potentials. However, our understanding of the basic molecular mechanisms that regulate myelination, demyelination and remyelination is limited. Schwann cells produce myelin in the peripheral nervous system and remain associated with the axons of peripheral neurons throughout axonal migration to the target. Owing to the intimate relationship between these cell types it is difficult to fully reproduce their function in vitro. For this reason, we developed an approach based on the injection of an engineered virus into the sciatic nerve of mice to locally transduce peripheral nerve cells. This approach can be used as an alternative to germline transgenesis to facilitate the investigation of peripheral nerve biology in vivo. The detailed protocol, described here, requires 3 weeks to complete. In comparison with genetic modification strategies, this protocol is a fast, reproducible and straightforward method for introducing exogenous factors into myelinating Schwann cells and myelinated axons in vivo to investigate specific molecular mechanisms. PMID:24762783

Gonzalez, Sergio; Fernando, Ruani N; Perrin-Tricaud, Claire; Tricaud, Nicolas

2014-05-01

206

Diffuse traumatic axonal injury in the optic nerve does not elicit retinal ganglion cell loss.  

Science.gov (United States)

Much of the morbidity after traumatic brain injury (TBI) is associated with traumatic axonal injury (TAI). Although most TAI studies focus on corpus callosum white matter, the visual system has received increased interest. To assess visual system TAI, we developed a mouse model of optic nerve TAI. It is unknown, however, whether this TAI causes retinal ganglion cell (RGC) death. To address this issue, YFP (yellow fluorescent protein)-16 transgenic mice were subjected to mild TBI and followed from 2 to 28 days. Neither TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive or cleaved caspase-3-immunoreactive RGCs were observed from 2 to 28 days after TBI. Quantification of immunoreactivity of Brn3a, an RGC marker, demonstrated no RGC loss; parallel electron microscopic analysis confirmed RGC viability. Persistent RGC survival was also consistent with the finding of reorganization in the proximal axonal segments after TAI, wherein microglia/macrophages remained inactive. In contrast, activated microglia/macrophages closely enveloped the distal disconnected, degenerating axonal segments at 7 to 28 days after injury, thereby confirming that this model consistently evoked TAI followed by disconnection. Collectively, these data provide novel insight into the evolving pathobiology associated with TAI that will form a foundation for future studies exploring TAI therapy and its downstream consequences. PMID:23860030

Wang, Jiaqiong; Fox, Michael A; Povlishock, John T

2013-08-01

207

Expression of a conserved cell-type-specific protein in nerve terminals coincides with synaptogenesis.  

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Contact of axons with target territories results in the formation of synapses, specific junctional complexes that may represent a final stage of neuronal maturation. Synaptosomal-associated protein 25 (SNAP-25) is a component of particular nerve terminals recently identified in rodent brain. To evaluate the structure and regulation of molecular components of the synapse, we investigated the expression of SNAP-25 in the developing chicken nervous system. Analysis of SNAP-25 cDNA clones demonstrated that the chicken homologue is identical in amino acid sequence to the mouse protein. In chicken retina and neural tube, the onset of SNAP-25 mRNA and protein expression was found to correspond to the time of synaptogenesis. These results suggest that SNAP-25 plays a role in the physiology of mature nerve terminals and that its expression may be regulated by specific cell-cell interactions occurring during synapse formation. PMID:1992470

Catsicas, S; Larhammar, D; Blomqvist, A; Sanna, P P; Milner, R J; Wilson, M C

1991-02-01

208

The effect of collagen-binding NGF-beta on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model.  

Science.gov (United States)

Nerve growth factor plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical application. It has demonstrated in our previous work that the native human NGF-beta (NAT-NGF) fused with a collagen-binding domain (CBD) could bind to collagen specifically. Since collagen is the major component of nerve extracellular matrix, we speculated that the collagen-binding NGF would target to nerve cells and improve their regeneration. In this report, we found that the fusion protein could specifically bind to endogenous collagen of the rat sciatic nerves and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that collagen-binding NGF could be retained and concentrated at the nerve injured site to promote nerve repair and enhance function recovery following nerve damage. Thus, the collagen-binding NGF could improve the repair of peripheral nerve injury. PMID:19573907

Sun, Wenjie; Sun, Changkai; Lin, Hang; Zhao, Hui; Wang, Jingyu; Ma, Hui; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu

2009-09-01

209

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

Science.gov (United States)

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

Yosef, Nejla; Ubogu, Eroboghene E

2013-03-01

210

Gastric myoelectrical activity increases after moderate-intensity exercise with no meals under suppressed vagal nerve activity.  

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Postprandial gastric myoelectrical activity recorded by electrogastrogram (EGG) with the subject in a supine position has shown to be enhanced after moderate-intensity pedaling exercise in an upright seated position, despite the suppression of vagal nerve activity. However, it is still unknown whether the effect is due to the exercise itself and/or a meal or how the position change has influenced the effects. To address this, we used a position-controllable cycle ergometer to examine the effects of the moderate-intensity exercise on EGG activity and the high-frequency (HF) component of heart rate variability (HRV), an index of vagal nerve activity. To eliminate the effect of position change, we carried out the exercise and the EGG recording in the supine position. The peak amplitude of the EGG was enhanced by prior moderate-intensity exercise with a reduced HF component of HRV, which did not differ for postexercise conditions with or without a meal. The small amount of meal itself, however, enhanced both the peak amplitude of the EGG and the HF component of HRV. The peak frequency of EGG was reduced and the instability coefficient of EGG was increased only after the exercise itself. Taken together, these results suggest that the enhanced amplitude of gastric myoelectrical activity can be induced by moderate-intensity exercise itself, even with suppressed vagal nerve activity, and that the mechanism underlying the exercise effects would differ from that underlying the effect of a meal alone. PMID:15541200

Kato, M; Sakai, T; Yabe, K; Miyamura, M; Soya, H

2004-06-01

211

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

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

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

1980-01-01

212

Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma  

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Nerve growth factor (NGF) is overexpressed not only in nervous system, but also in several types of cancers. However, the role of NGF in oesophageal squamous cell carcinoma (OESCC) remains unclear. Here, we show the first evidence of NGF-TrkA autocrine loop and clinical significance of NGF overexpression in OESCC. Immunohistochemical study of 109 OESCC specimens revealed that NGF overexpression, found in 63 out of 109 patients (57.8%), was associated with lymph node metastasis, distant metast...

2006-01-01

213

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

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

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

2014-05-15

214

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

Science.gov (United States)

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. PMID:21544670

Harreby, Kristian R; Sevcencu, Cristian; Struijk, Johannes J

2011-09-01

215

Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans  

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We sought to determine whether carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) was altered during dynamic exercise. In five men and three women, 23.8 +/- 0.7 (SE) yr of age, CBR function was evaluated at rest and during 20 min of arm cycling at 50% peak O(2) uptake using 5-s periods of neck pressure and neck suction. From rest to steady-state arm cycling, mean arterial pressure (MAP) was significantly increased from 90.0 +/- 2.7 to 118.7 +/- 3.6 mmHg and MSNA burst frequency (microneurography at the peroneal nerve) was elevated by 51 +/- 14% (P < 0.01). However, despite the marked increases in MAP and MSNA during exercise, CBR-Delta%MSNA responses elicited by the application of various levels of neck pressure and neck suction ranging from +45 to -80 Torr were not significantly different from those at rest. Furthermore, estimated baroreflex sensitivity for the control of MSNA at rest was the same as during exercise (P = 0.74) across the range of neck chamber pressures. Thus CBR control of sympathetic nerve activity appears to be preserved during moderate-intensity dynamic exercise.

Fadel, P. J.; Ogoh, S.; Watenpaugh, D. E.; Wasmund, W.; Olivencia-Yurvati, A.; Smith, M. L.; Raven, P. B.

2001-01-01

216

Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia.  

Science.gov (United States)

Familial dysautonomia (Riley-Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

2013-02-01

217

Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown. Methods Using the rat spared nerve injury (SNI model, we investigated the expression of PAF synthases (LPCAT1 and 2 and PAF receptor (PAFr mRNAs in the spinal cord. Reverse transcription polymerase chain reaction (RT-PCR and double-labeling analysis of in situ hybridization histochemistry (ISHH with immunohistochemistry (IHC were employed for the analyses. Pain behaviors were also examined with PAFr antagonist (WEB2086. Results RT-PCR showed that LPCAT2 mRNA was increased in the ipsilateral spinal cord after injury, but not LPCAT1 mRNA. Double-labeling of ISHH with IHC revealed that LPCAT1 and 2 mRNAs were constitutively expressed by a subset of neurons, and LPCAT2 mRNA was increased in spinal microglia after nerve injury. RT-PCR showed that PAFr mRNA was dramatically increased in the ipsilateral spinal cord after nerve injury. Double-labeling analysis of ISHH with IHC revealed that after injury PAFr mRNA was predominantly colocalized with microglia in the spinal cord. Continuous intrathecal administration of the PAFr antagonist suppressed mechanical allodynia following peripheral nerve injury. Delayed administration of a PAFr antagonist did not reverse the mechanical allodynia. Conclusions Our data show the histological localization of PAF synthases and its receptor in the spinal cord following peripheral nerve injury, and suggest that PAF/PAFr signaling in the spinal cord acts in an autocrine or paracrine manner among the activated microglia and neurons, thus contributing to development of neuropathic pain.

Okubo Masamichi

2012-02-01

218

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

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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...

Lorber, Barbara; Tassoni, Alessia; Bull, Natalie D.; Moschos, Marilita M.; Martin, Keith R.

2012-01-01

219

The fusion of bone-marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy  

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Diabetic neuropathy is the most common microvascular complication of diabetes. Here we show that, in streptozotocin-induced diabetic rodents with neuropathy, a subpopulation of bone-marrow-derived cells marked by proinsulin expression migrates to and fuses with neurons in the sciatic nerve and dorsal root ganglion (DRG), resulting in neuronal dysfunction and accelerated apoptosis. The absence or presence of proinsulin expression, which identifies the fusion cells, and not the disease state (n...

2005-01-01

220

Degenerative Nerve Diseases  

Science.gov (United States)

Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

 
 
 
 
221

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

Science.gov (United States)

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test hybrid chitosan membranes to use in peripheral nerve reconstruction, either alone or enriched with N1E-115 neural cells. Hybrid chitosan membranes were tested in vitro, to assess their ability in supporting N1E-115 cell survival and differentiation, and in vivo to assess biocompatibility as well as to evaluate their effects on nerve fiber regeneration and functional recovery after a standardized rat sciatic nerve crush injury. Functional recovery was evaluated using the sciatic functional index (SFI), the static sciatic index (SSI), the extensor postural thrust (EPT), the withdrawal reflex latency (WRL) and ankle kinematics. Nerve fiber regeneration was assessed by quantitative stereological analysis and electron microscopy. All chitosan membranes showed good biocompatibility and proved to be a suitable substrate for plating the N1E-115 cellular system. By contrast, in vivo nerve regeneration assessment after crush injury showed that the freeze-dried chitosan type III, without N1E-115 cell addition, was the only type of membrane that significantly improved posttraumatic axonal regrowth and functional recovery. It can be thus suggested that local enwrapping with this type of chitosan membrane may represent an effective approach for the improvement of the clinical outcome in patients receiving peripheral nerve surgery. PMID:18723219

Amado, S; Simões, M J; Armada da Silva, P A S; Luís, A L; Shirosaki, Y; Lopes, M A; Santos, J D; Fregnan, F; Gambarotta, G; Raimondo, S; Fornaro, M; Veloso, A P; Varejão, A S P; Maurício, A C; Geuna, S

2008-11-01

222

Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury  

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Abstract Background Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown.

Okubo Masamichi; Yamanaka Hiroki; Kobayashi Kimiko; Kanda Hirosato; Dai Yi; Noguchi Koichi

2012-01-01

223

Induction of parathyroid hormone-related peptide following peripheral nerve injury: role as a modulator of Schwann cell phenotype.  

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Parathyroid hormone-related peptide (PTHrP) is widely distributed in the rat nervous system, including the peripheral nervous system, where its function is unknown. PTHrP mRNA expression has recently been shown to be significantly elevated following axotomy of sympathetic ganglia, although the role of PTHrP was not investigated. The role of PTHrP in peripheral nerve injury was investigated in this study using the sciatic nerve injury model and dorsal root ganglion (DRG) explant model of nerve regeneration. We find that PTHrP is a constitutively secreted peptide of proliferating Schwann cells and that the PTHrP receptor (PTH1R) mRNA is expressed in isolated DRG and in sciatic nerve. Using the sciatic nerve injury model, we show that PTHrP is significantly upregulated in DRG and in sciatic nerve. In addition, in situ hybridization revealed significant localization of PTHrP mRNA to Schwann cells in the injured sciatic nerve. We also find that PTHrP causes a dramatic increase in the number of Schwann cells that align with and bundle regrowing axons in explants, characteristic of immature, dedifferentiated Schwann cells. In addition to stimulating migration of Schwann cells along the axonal membrane, PTHrP also stimulates migration on a type 1 collagen matrix. Furthermore, treatment of purified Schwann cell cultures with PTHrP results in the rapid phosphorylation of the cAMP response element protein, CREB. We propose that PTHrP acts by promoting the dedifferentiation of Schwann cells, a critical requirement for successful nerve regeneration and an effect consistent with known PTHrP functions in other cellular differentiation programs. PMID:16470617

Macica, Carolyn M; Liang, Guoying; Lankford, Karen L; Broadus, Arthur E

2006-04-15

224

Combination of G-CSF administration and human amniotic fluid mesenchymal stem cell transplantation promotes peripheral nerve regeneration.  

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Amniotic fluid mesenchymal stem cells (AFS) harbor the potential to improve peripheral nerve injury by inherited neurotrophic factor secretion, but present the drawback of the short-term survival after transplantation. Granulocyte-colony stimulating factor (G-CSF) has a diversity of functions, including anti-inflammatory and anti-apoptotic effects. This study was conducted to evaluate whether G-CSF could augment the neuroprotective effect of transplanted AFS against peripheral nerve injury. The potential involvement of anti-inflammation/anti-apoptosis effect was also investigated. Peripheral nerve injury was produced in Sprauge-Dawley rats by crushing left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. G-CSF (50 microg/kg) was administrated by intra-peritoneal injection for 7 consecutive days. Cell apoptosis, inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. Crush injury induced inflammatory response, disrupted nerve integrity, and impaired nerve function in sciatic nerve. Crush injury-provoked inflammation was attenuated in groups receiving G-CSF but not in AFS only group. In transplanted AFS, marked apoptosis was detected and this event was reduced by G-CSF treatment. Increased nerve myelination and improved motor function were observed in AFS transplanted, G-CSF administrated, and AFS/G-CSF combined treatment groups. Significantly, the combined treatment showed the most beneficial effect. In conclusion, the concomitant treatment of AFS with G-CSF augments peripheral nerve regeneration which may involve the suppression of apoptotic death in implanted AFS and the attenuation of inflammatory response. PMID:18690534

Pan, Hung-Chuan; Chen, Chung-Jung; Cheng, Fu-Chou; Ho, Shu-Pen; Liu, Mu-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Wang, Yeou-Chih

2009-03-01

225

Normal molecular repair mechanisms in regenerative peripheral nerve interfaces allow recording of early spike activity despite immature myelination.  

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Clinical use of neurally controlled prosthetics has advanced in recent years, but limitations still remain, including lacking fine motor control and sensory feedback. Indwelling multi-electrode arrays, cuff electrodes, and regenerative sieve electrodes have been reported to serve as peripheral neural interfaces, though long-term stability of the nerve-electrode interface has remained a formidable challenge. We recently developed a regenerative multi-electrode interface (REMI) that is able to record neural activity as early as seven days post-implantation. While this activity might represent normal neural depolarization during axonal regrowth, it can also be the result of altered nerve regeneration around the REMI. This study evaluated high-throughput expression levels of 84 genes involved in nerve injury and repair, and the histological changes that occur in parallel to this early neural activity. Animals exhibiting spike activity increased from 29% to 57% from 7 to 14 days following REMI implantation with a corresponding increase in firing rate of 113%. Two weeks after implantation, numbers of neurofilament-positive axons in the control and REMI implanted nerves were comparable, and in both cases the number of myelinated axons was low. During this time, expression levels of genes related to nerve injury and repair were similar in regenerated nerves, both in the presence or absence of the electrode array. Together, these results indicate that the early neural activity is intrinsic to the regenerating axons, and not induced by the REMI neurointerface. PMID:22203723

Seifert, Jennifer L; Desai, Vidhi; Watson, Robert C; Musa, Tabassum; Kim, Young-tae; Keefer, Edward W; Romero, Mario I

2012-03-01

226

In vivo effects of leptin on autonomic nerve activity and lipolysis in rats.  

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Leptin, a 16-kDa protein, is produced by white adipose tissue (WAT), and is thought to serve as a feedback signal indicating the size of fat stores. Considerable amount of data have shown that leptin can mediate lipid metabolism. However, its possible direct effects on the metabolism of lipids in vivo and the mechanisms involved have not been fully characterized. In this study, we investigated the in vivo effects of leptin on the autonomic nerve activity and lipolysis. We found that intravenous administration of leptin (10 microg/rat) excited the sympathetic nerves innervating WAT, and this effect was abolished by the pretreatment with diphenhydramine, a histamine H(1) receptor antagonist. Moreover, intraperitoneal administration of leptin (130 microg/kg) elevated the levels of plasma glycerol and free fatty acid (FFA). The effect of leptin on plasma FFA was eliminated by pretreatment with diphenhydramine and propranolol, a beta-adrenergic receptor blocker, and disappeared in suprachiasmatic nucleus (SCN)-lesioned rats. Our results suggest that leptin might regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nerves, driven by histamine neurons through the H(1) receptor, and a beta-adrenergic receptor, probably the beta(3)-receptor, is involved in the lipolytic response to leptin. The actions of leptin in this study are supposed to be controlled by the SCN. PMID:17306457

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

2007-04-12

227

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

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

Gemes Geza

2012-06-01

228

Comparison of beneficial effects of undifferentiated cultured bone marrow stromal cells and omental adipose-derived nucleated cell fractions on sciatic nerve regeneration.  

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Adipose tissue is a good source for isolation of cells with stem-cell-like properties. The effects of undifferentiated cultured bone marrow stromal cells (BMSCs) and omental adipose-derived nucleated cells (OADNCs) on peripheral nerve regeneration were compared in a rat nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a vein graft. In one group, the vein was filled with BMSCs and in the other group with OADNCs. Functional study, morphometric indices, and immunohistochemistry indicated there was no significant difference (P > 0.05) between groups in recovery of regenerated axons at 4, 8, and 12 weeks after surgery. OADNCs enhanced regeneration similar to undifferentiated BMSCs. These observations suggest OADNCs represent an effective and cost-saving cell population due to the shortened time interval from tissue collection to cell injection as well as procedural simplicity. This approach is clinically translatable toward new methods for enhanced peripheral nerve repair without the limitations of BMSC. PMID:21254077

Mohammadi, Rahim; Azizi, Saeed; Delirezh, Nowruz; Hobbenaghi, Rahim; Amini, Keyvan

2011-02-01

229

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

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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. PMID:22869011

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

2012-10-01

230

Recovery of baroreflex control of renal sympathetic nerve activity after spinal lesions in the rat.  

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Spinal cord injury (SCI) has serious long-term consequences on sympathetic cardiovascular regulation. Orthostatic intolerance results from insufficient baroreflex regulation (BR) of sympathetic outflow to maintain proper blood pressure upon postural changes. Autonomic dysreflexia occurs due to insufficient inhibition of spinal sources of sympathetic activity. Both of these conditions result from the inability to control sympathetic activity caudal to SCI. It is well established that limited motor ability recovers after incomplete SCI. Therefore, the goal of this study was to determine whether recovery of BR occurs after chronic, left thoracic spinal cord hemisection at either T(3) or T(8). Baroreflex tests were performed in rats by measuring the reflex response of left (ipsilateral) renal sympathetic nerve activity to decreases and increases in arterial pressure produced by ramped infusions of sodium nitroprusside and phenylephrine, respectively. One week after a T(3) left hemisection, BR function was modestly impaired. However, 8 wk after a T(3) left hemisection, BR function was normal. One week after a T(8) left hemisection, BR function was significantly impaired, and 8 wk after a T(8) left hemisection, BR function was significantly improved. These results indicate that BR of renal sympathetic nerve activity in rats may partially recover after spinal cord hemisections, becoming normal by 8 wk after a T(3) lesion, but not after a T(8) lesion. The nature of the spinal cord and/or brain stem reorganization that mediates this recovery remains to be determined. PMID:21900643

Zahner, Matthew R; Kulikowicz, Ewa; Schramm, Lawrence P

2011-11-01

231

Possible genetic influence on the strength of human muscle nerve sympathetic activity at rest.  

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Large reproducible interindividual differences in the strength of human muscle nerve sympathetic activity have been demonstrated previously without satisfactory explanation. We undertook the present study to investigate whether a genetic influence may be a factor of importance. Microneurographic recordings of sympathetic impulse traffic were made in the peroneal nerve in nine pairs of monozygotic male twins and eight pairs of age-matched male subjects without family relationship. The strength of the sympathetic activity was quantitated as number of sympathetic bursts per 100 heart beats and bursts per minute. Group mean values of muscle sympathetic activity, heart rate, and blood pressure were similar in the two groups. Intrapair differences (mean +/- SEM) of sympathetic activity were 5.4 +/- 1.7 bursts per 100 heart beats (1.7 +/- 0.5 bursts per minute) for the twins and 19.4 +/- 3.2 bursts per 100 heart beats (11.8 +/- 2.5 bursts per minute) for the control subjects (P < .01 for both). The degree of reproducibility between twins is similar to that reported previously between repeated recordings in the same subject. The finding may indicate that the strength of sympathetic outflow to muscle is controlled genetically. If so, we speculate that this may contribute to the heritability of blood pressure in both normotensive and hypertensive subjects. PMID:8349319

Wallin, B G; Kunimoto, M M; Sellgren, J

1993-09-01

232

Abnormal intracellular calcium homeostasis associated with vulnerability in the nerve cells from heroin-dependent rat.  

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The cellular mechanisms by which opiate addiction develops with repetitive use remain largely unresolved. Intercellular calcium homeostasis is one of the most critical elements to determine neuroadaptive changes and neuronal fate. Heroin, one of the most addictive opiates, may induce neurotoxicity potentially inducing brain impairment, especially for those chronic users who get an overdose. Here we examined changes in intracellular calcium concentration ([Ca(2+)]i) after repeated exposure to heroin using cultured cerebral cortical neurons. Dynamic changes in [Ca(2+)]i indicated by fluo-3-AM were monitored using confocal laser scan microscopy, followed by cytotoxicity assessments. It showed that the cells dissociated from heroin-dependent rats had a smaller depolarization-induced [Ca(2+)]i responses, and a higher elevation in [Ca(2+)]i when challenged with a high concentration of heroin (500?M). The restoration ability to remove calcium after washout of these stimulants was impaired. Calcium channel blocker verapamil inhibited the heroin-induced [Ca(2+)]i elevations as well as the heroin-induced cell damage. The relative [Ca(2+)]i of the nerve cells closely correlated with the number of damaged cells induced by heroin. These results demonstrate that nerve cells from heroin-dependent rats manifest abnormal [Ca(2+)]i homeostasis, as well as vulnerability to heroin overdose, suggesting involvement of [Ca(2+)]i regulation mechanisms in heroin addiction and neurotoxicity. PMID:24854119

Liu, Xiaoshan; Wang, Guangyong; Pu, Hongwei; Jing, Hualan

2014-07-14

233

Mast cell activation disorders.  

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Disorders associated with mast cell activation range from relatively common IgE-mediated disease and chronic urticaria to rarer conditions such as mastocytosis or monoclonal mast cell activation disorder. Mast cell activation disorders can be mechanistically classified into primary (associated with abnormal production of mast cells that carry pathologic markers of clonality), secondary (normal mast cells activated in reaction to a microenvironmental trigger), and idiopathic (no etiology is found). Clinical presentations, diagnostic criteria as well as general principles of a stepwise therapy approach are discussed. PMID:24811013

Akin, Cem

2014-01-01

234

Autoimmune T cells retard the loss of function in injured rat optic nerves.  

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We recently demonstrated that autoimmune T cells protect neurons from secondary degeneration after central nervous system (CNS) axotomy in rats. Here we show, using both morphological and electrophysiological analyses, that the neuroprotection is long-lasting and is manifested functionally. After partial crush injury of the rat optic nerve, systemic injection of autoimmune T cells specific to myelin basic protein significantly diminished the loss of retinal ganglion cells and conducting axons, and significantly retarded the loss of the visual response evoked by light stimulation. These results support our challenge to the traditional concept of autoimmunity as always harmful, and suggest that in certain situations T cell autoimmunity may actually be beneficial. It might be possible to employ T cell intervention to slow down functional loss in the injured CNS. PMID:10814797

Moalem, G; Yoles, E; Leibowitz-Amit, R; Muller-Gilor, S; Mor, F; Cohen, I R; Schwartz, M

2000-07-01

235

Biphasic effects of orexin-A on autonomic nerve activity and lipolysis.  

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Previously, we showed that orexin-A, a 33-aa peptide, influences renal sympathetic nerve activity. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of orexin-A on the sympathetic nerve activity innervating white adipose tissue (WAT-SNA) and lipolysis. We found that intracerebroventricular (icv) administration of orexin-A at doses of 1 microg/rat and 10 ng/rat elevated and suppressed WAT-SNA, respectively. The effect of the high dose of orexin-A (1 microg/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of the low dose of orexin-A (10 ng/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, icv administration of 1 microg/rat and 10 ng/rat of orexin-A increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The effect of 1 microg/rat of orexin-A on plasma FFA was eliminated by propranolol hydrochloride, a beta-adrenergic receptor blocker, and also by diphenhydramine. The effect of orexin-A at dose of 10 ng/rat disappeared by pretreatment with atropine sulfate, a muscarinic receptor blocker, and thioperamide maleate salt. Our results suggest that high doses of orexin-A may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H(1) receptor, and that the beta(3)-receptor may be involved in this enhanced lipolytic response. Low doses of orexin-A, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H(3)-receptor, and the muscarinic receptor may be related to this response. PMID:18755242

Shen, Jiao; Tanida, Mamoru; Yao, Jia-Fei; Niijima, Akira; Nagai, Katsuya

2008-10-24

236

Selective electrical stimulation of the auditory nerve activates a pathway specialized for high temporal acuity.  

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Deaf people who use cochlear implants show surprisingly poor sensitivity to the temporal fine structure of sounds. One possible reason is that conventional cochlear implants cannot activate selectively the auditory-nerve fibers having low characteristic frequencies (CFs), which, in normal hearing, phase lock to stimulus fine structure. Recently, we tested in animals an alternative mode of auditory prosthesis using penetrating auditory-nerve electrodes that permit frequency-specific excitation in all frequency regions. We present here measures of temporal transmission through the auditory brainstem, from pulse trains presented with various auditory-nerve electrodes to phase-locked activity of neurons in the central nucleus of the inferior colliculus (ICC). On average, intraneural stimulation resulted in significant ICC phase locking at higher pulse rates (i.e., higher "limiting rates") than did cochlear-implant stimulation. That could be attributed, however, to the larger percentage of low-CF neurons activated selectively by intraneural stimulation. Most ICC neurons with limiting rates >500 pulses per second had CFs <1.5 kHz, whereas neurons with lower limiting rates tended to have higher CFs. High limiting rates also correlated strongly with short first-spike latencies. It follows that short latencies correlated significantly with low CFs, opposite to the correlation observed with acoustical stimulation. These electrical-stimulation results reveal a high-temporal-acuity brainstem pathway characterized by low CFs, short latencies, and high-fidelity transmission of periodic stimulation. Frequency-specific stimulation of that pathway by intraneural stimulation might improve temporal acuity in human users of a future auditory prosthesis, which in turn might improve musical pitch perception and speech reception in noise. PMID:20130202

Middlebrooks, John C; Snyder, Russell L

2010-02-01

237

Adenoviral-mediated glial cell line-derived neurotrophic factor gene transfer has a protective effect on sciatic nerve following constriction-induced spinal cord injury.  

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Neuropathic pain due to peripheral nerve injury may be associated with abnormal central nerve activity. Glial cell-line-derived neurotrophic factor (GDNF) can help attenuate neuropathic pain in different animal models of nerve injury. However, whether GDNF can ameliorate neuropathic pain in the spinal cord dorsal horn (SCDH) in constriction-induced peripheral nerve injury remains unknown. We investigated the therapeutic effects of adenoviral-mediated GDNF on neuropathic pain behaviors, microglial activation, pro-inflammatory cytokine expression and programmed cell death in a chronic constriction injury (CCI) nerve injury animal model. In this study, neuropathic pain was produced by CCI on the ipsilateral SCDH. Mechanical allodynia was examined with von Frey filaments and thermal sensitivity was tested using a plantar test apparatus post-operatively. Target proteins GDNF-1, GDNFRa-1, MMP2, MMP9, p38, phospho-p38, ED1, IL6, IL1?, AIF, caspase-9, cleaved caspase-9, caspase-3, cleaved caspase-3, PARP, cleaved PARP, SPECTRIN, cleaved SPECTRIN, Beclin-1, PKC?, PKC?, iNOS, eNOS and nNOS were detected. Microglial activity was measured by observing changes in immunoreactivity with OX-42. NeuN and TUNEL staining were used to reveal whether apoptosis was attenuated by GDNF. Results showed that administrating GDNF began to attenuate both allodynia and thermal hyperalgesia at day 7. CCI-rats were found to have lower GDNF and GDNFRa-1 expression compared to controls, and GDNF re-activated their expression. Also, GDNF significantly down-regulated CCI-induced protein expression except for MMP2, eNOS and nNOS, indicating that the protective action of GDNF might be associated with anti-inflammation and prohibition of microglia activation. Immunocytochemistry staining showed that GDNF reduced CCI-induced neuronal apoptosis. In sum, GDNF enhanced the neurotrophic effect by inhibiting microglia activation and cytokine production via p38 and PKC signaling. GDNF could be a good therapeutic tool to attenuate programmed cell death, including apoptosis and autophagy, consequent to CCI-induced peripheral nerve injury. PMID:24642655

Chou, An-Kuo; Yang, Ming-Chang; Tsai, Hung-Pei; Chai, Chee-Yin; Tai, Ming-Hong; Kwan, Aij-Li; Hong, Yi-Ren

2014-01-01

238

Calcineurin controls nerve activity-dependent specification of slow skeletal muscle fibers but not muscle growth  

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Nerve activity can induce long-lasting, transcription-dependent changes in skeletal muscle fibers and thus affect muscle growth and fiber-type specificity. Calcineurin signaling has been implicated in the transcriptional regulation of slow muscle fiber genes in culture, but the functional role of calcineurin in vivo has not been unambiguously demonstrated. Here, we report that the up-regulation of slow myosin heavy chain (MyHC) and a MyHC-slow promoter induced by slow motor neurons in regener...

Serrano, Antonio L.; Murgia, Marta; Pallafacchina, Giorgia; Calabria, Elisa; Coniglio, Patrizia; Lømo, Terje; Schiaffino, Stefano

2001-01-01

239

Pinched Nerve  

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

240

Regional venous outflow, blood volume, and sympathetic nerve activity during severe hypoxia.  

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We examined the dynamic changes in venous outflow from the splanchnic, coronary, and remaining other vascular beds and changes in systemic blood volume (SBV) in response to severe hypoxia (PO2 = 17 mmHg) in dogs using cardiopulmonary bypass and a reservoir. Splanchnic venous outflow, which also includes renal outflow in this study, decreased by 40%, and coronary venous outflow increased by 400% at 3.5 min after initiating severe hypoxia. Severe hypoxia caused a marked decrease in SBV of 23 +/- 1 and 9 +/- 2 ml/kg in spleen-intact and splenectomized dogs, respectively. The decrease in SBV was attenuated by 60 (P less than 0.01) and 83% (P less than 0.01) after the carotid and aortic chemoreceptor denervation (which was accompanied by baroreceptor denervation) and after hexamethonium infusion (10 mg/kg), respectively. Sympathetic efferent nerve activity revealed a tremendous augmentation, which began to rise at a PO2 of 40 mmHg before chemoreceptor denervation and at a PO2 of 22 mmHg after denervation. These results show that severe hypoxia causes a marked decrease in SBV, 60% of which is caused by active splenic contraction, and suggest that the sympathetic efferent nerve activity, which is augmented by the stimulation of chemoreceptors as well as the central nervous system, contributes greatly to those hypoxic changes. PMID:2912179

Hoka, S; Bosnjak, Z J; Arimura, H; Kampine, J P

1989-01-01

 
 
 
 
241

Channels Active in the Excitability of Nerves and Skeletal Muscles across the Neuromuscular Junction: Basic Function and Pathophysiology  

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Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the…

Goodman, Barbara E.

2008-01-01

242

Three-dimensional alignment of schwann cells using hydrolysable microfiber scaffolds: strategies for peripheral nerve repair.  

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Injuries to the peripheral nervous system affect 1 in 1,000 individuals each year. The implication of sustaining such an injury is considerable with loss of sensory and/or motor function. The economic implications too are extensive running into millions of pounds (or dollars) annually for provision and support. The natural regrowth of peripheral nerves is possible for small gap injuries (of approximately 1-2 mm). However, patients with larger gap injuries require surgical intervention. The "gold standard" for repairing gap injuries is autografting; however, there are problems associated with this approach, and so, the use of nerve guidance conduits (NGC) is a realistic alternative. We outline in this chapter the development of an NGC that incorporates aligned poly-L-lactide fibres for supporting the growth of organised Schwann cells within a three-dimensional scaffold in vitro. A closed loop bioreactor for growing cells within NGC scaffolds is described together with a method of plasma deposition for modifying the microfibre surface chemistry (which improves the ability of Schwann cells to attach) and confocal microscopy for measuring cell viability and alignment within 3D constructs. PMID:21042971

Murray-Dunning, Celia; McArthur, Sally L; Sun, Tao; McKean, Rob; Ryan, Anthony J; Haycock, John W

2011-01-01

243

Endopeptidase-24.11 is suppressed in myelin-forming but not in non-myelin-forming Schwann cells during development of the rat sciatic nerve.  

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Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukemia antigen (CALLA), is a cell surface zinc metalloprotease that has the ability to hydrolyse a variety of physiologically active peptides. Interest in this enzyme is based on the view that it may play a role in the regulation of peptide signals in different tissues, including the nervous and immune systems. We have previously shown that endopeptidase-24.11 is present in Schwann cells in the peripheral nervous system of newborn pigs [Kioussi C. and Matsas R. (1991) J. Neurochem. 57, 431-440]. In the present study we have investigated the developmental expression of the endopeptidase by Schwann cells in the rat sciatic nerve, from embryonic day 16 to maturity. Endopeptidase-24.11 was monitored enzymatically as well as by immunoblotting and immunocytochemistry using the monoclonal anti-endopeptidase antibody 23B11. We found an age-dependent decline in both the enzyme activity and the levels of immunoreactive protein. Endopeptidase-24.11 was first detected at embryonic day 18 and was present in all neonatal and early postnatal Schwann cells. However, as myelination proceeded the endopeptidase was gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. At this stage, only very few large diameter myelinated fibers expressed weakly endopeptidase-24.11. Schwann cells dissociated from postnatal day 5 nerves and cultured up to one week in the absence of axons expressed endopeptidase-24.11. These results show that the endopeptidase has a distinct developmental profile in the rat sciatic nerve, similar to that of a group of other Schwann cell surface antigens, including the cell adhesion molecules N-CAM and L1 and the nerve growth factor receptor. We suggest that, as is the case with these antigens, endopeptidase-24.11 may play a role in nerve development and/or regeneration. In addition, persistence of endopeptidase-24.11 in a minority of adult myelin-forming Schwann cells suggests a possible role for the enzyme in axon-myelin apposition and maintenance, especially of larger diameter axons. PMID:1407560

Kioussi, C; Crine, P; Matsas, R

1992-09-01

244

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

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

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

2014-01-01

245

Role of S-100 Immunostaining in Demonstration of Nerve Changes and Quantification of Dendritic Cells in Leprosy  

Science.gov (United States)

Background: A definitive diagnosis of leprosy is based on a demonstration of either acid-fast bacilli or nerve elements within the granulomas. On routine hematoxylin and eosin stains, the nerve fibers are not easily identifiable. In this study, S-100 immunostain is used to highlight the nerve elements and to demonstrate and compare the nerve changes in spectrum of leprosy including reactions. Aim: To demonstrate the nerve changes in spectrum of leprosy using S-100 immunostaining so as to categorize them for the purpose of early diagnosis and treatment. We also want to demonstrate and quantify the dendritic cells in lepromatous spectrum of leprosy using S-100 immunostain. Materials and Methods: Twenty consecutive skin biopsy specimens from patients with histopathological diagnosis of leprosy in the year 2012 were studied. Of these 20 cases, 13 were Borderline Tuberculoid, 1 was of indeterminate leprosy, 1 Borderline Lepromatous, 2 cases of Lepromatous Lep-rosy , 1 case of Type 1 reac-tion and 2 cases of Type 2 reaction. Stains used were Hematoxylin and Eosin stain for the histopathological diagnosis, Fites stain for Bacillary index and S-100 immunoperoxidase staining for nerve changes. 5 cases of granulomatous dermatosis of skin other than leprosy (5 cases of lupus vulgaris) were included as controls. Results: On Hematoxylin and Eosin staining, the nerve fibers showed vertical orientation in relation to epidermis in Borderline Tuberculoid leprosy. In addition , the nerve fibers showed rounded contour in Tuberculoid leprosy. The entire spectrum of leprosy showed evidence of nerve damage in S-100 immunostaining which was categorized in 4 patterns 1. Absent, 2. Fragmented, 3. Discontinuous and 4. Intact. The majority of Borderline Tuberculoid leprosy cases showed absent pattern of nerve damage. Dendritic cells were also positive for S-100 immunostaining with granular positivity in Borderline Tuberculoid Leprosy cases and membranous positivity in Lepromatous spectrum. Conclusion: Nerve damage is seen across the entire spectrum of leprosy and the early identification of this nerve damage using S-100 immunostaining, helps to differentiate between Lepromatous and Tuberculoid leprosy, especially in the borderline and indeterminate forms.

Mohanraj, Anand; Srinivasan, Sowmya

2014-01-01

246

Effects of culture supernatant from Lactobacillus pentosus strain S-PT84 on autonomic nerve activity in rats.  

Science.gov (United States)

Intestinal administration of various lactobacilli has been reported to affect autonomic neurotransmission, blood pressure, blood glucose, and body weight in rats, however, the mechanisms of action of the lactobacilli remain to be clarified. Therefore, the effect of the culture supernatant of Lactobacillus pentosus strain S-PT84 on the autonomic nerve activity in urethane-anesthetized rats was investigated. Intraduodenal injection of the low-molecular-weight (LMW) fraction (molecules less than 10,000 Da) of the S-PT84 culture supernatant elevated the brown adipose tissue sympathetic nerve activity and reduced the gastric vagal nerve activity. Moreover, intraoral administration of this LMW fraction increased the body temperature of rats above the interscapular brown adipose tissue. These results suggest that the LMW fraction of the S-PT84 culture supernatant affects the autonomic nerve activity and thermogenesis, and that the change in thermogenesis may be caused by the change in the sympathetic nerve activity of brown adipose tissue. PMID:22523286

Beppu, Yoshinori; Izumo, Takayuki; Horii, Yuko; Shen, Jiao; Fujisaki, Yoshiyuki; Nakashima, Toshihiro; Tsuruoka, Nobuo; Nagai, Katsuya

2012-01-01

247

Changes in sensory activity of ocular surface sensory nerves during allergic keratoconjunctivitis.  

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Peripheral neural mechanisms underlying the sensations of irritation, discomfort, and itch accompanying the eye allergic response have not been hitherto analyzed. We explored this question recording the changes in the electrical activity of corneoconjunctival sensory nerve fibers of the guinea pig after an ocular allergic challenge. Sensitization was produced by i.p. ovalbumin followed by repeated application in the eye of 10% ovalbumin on days 14 to 18. Blinking and tearing rate were measured. Spontaneous and stimulus-evoked (mechanical, thermal, chemical) impulse activity was recorded from mechanonociceptor, polymodal nociceptor and cold corneoscleral sensory afferent fibers. After a single (day 14) or repeated daily exposures to the allergen during the following 3 to 4days, tearing and blinking rate increased significantly. Also, sensitization was observed in mechanonociceptors (transient reduction of mechanical threshold only on day 14) and in polymodal nociceptors (sustained enhancement of the impulse response to acidic stimulation). In contrast, cold thermoreceptors showed a significant decrease in basal ongoing activity and in the response to cooling. Treatment with the TRPV1 and TRPA1 blockers capsazepine and HC-030031 reversed the augmented blinking. Only capsazepine attenuated tearing rate increase and sensitization of the polymodal nociceptors response to CO2. Capsazepine also prevented the decrease in cold thermoreceptor activity caused by the allergic challenge. We conclude that changes in nerve impulse activity accompanying the ocular allergic response, primarily mediated by activation of nociceptor's TRPV1 and to a lesser degree by activation of TRPA1 channels, explain the eye discomfort sensations accompanying allergic episodes. PMID:23867735

Acosta, M Carmen; Luna, Carolina; Quirce, Susana; Belmonte, Carlos; Gallar, Juana

2013-11-01

248

Functional recoveries of sciatic nerve regeneration by combining chitosan-coated conduit and neurosphere cells induced from adipose-derived stem cells.  

Science.gov (United States)

Suboptimal repair occurs in a peripheral nerve gap, which can be partially restored by bridging the gap with various biosynthetic conduits or cell-based therapy. In this study, we developed a combination of chitosan coating approach to induce neurosphere cells from human adipose-derived stem cells (ASCs) on chitosan-coated plate and then applied these cells to the interior of a chitosan-coated silicone tube to bridge a 10-mm gap in a rat sciatic nerve. Myelin sheath degeneration and glial scar formation were discovered in the nerve bridged by the silicone conduit. By using a single treatment of chitosan-coated conduit or neurosphere cell therapy, the nerve gap was partially recovered after 6 weeks of surgery. Substantial improvements in nerve regeneration were achieved by combining neurosphere cells and chitosan-coated conduit based on the increase of myelinated axons density and myelin thickness, gastrocnemius muscle weight and muscle fiber diameter, and step and stride lengths from gait analysis. High expressions of interleukin-1? and leukotriene B4 receptor 1 in the intra-neural scarring caused by using silicone conduits revealed that the inflammatory mechanism can be inhibited when the conduit is coated with chitosan. This study demonstrated that the chitosan-coated surface performs multiple functions that can be used to induce neurosphere cells from ASCs and to facilitate nerve regeneration in combination with a cells-assisted coated conduit. PMID:24360575

Hsueh, Yuan-Yu; Chang, Ya-Ju; Huang, Tzu-Chieh; Fan, Shih-Chen; Wang, Duo-Hsiang; Chen, Jia-Jin Jason; Wu, Chia-Ching; Lin, Sheng-Che

2014-02-01

249

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

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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 B...

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

2013-01-01

250

Primary CD56-positive NK/T-cell lymphoma of median nerve: a case report.  

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Primary extranodal lymphomas of the central nervous system constitute 2% of all malignant lymphomas. The involvement of the peripheral nervous system is very rare. A solitary primary CD56-positive NK/T-cell lymphoma of the median nerve is described in a 70-year-old woman. On physical examination, a rubbery hard mass measuring 2.0 cm in diameter was palpated on the volar aspect of second to third finger of left hand. Excisional biopsy was performed. Under the fascia, a large fusiform tumor of ...

Kim, J.; Kim, Y. S.; Lee, E. J.; Kang, C. S.; Shim, S. I.

1998-01-01

251

[Changes in the excitability of central endings of the superior laryngeal nerve following activation of the respiratory center].  

Science.gov (United States)

Changes in polarization of central afferent terminals of the superior laryngeal nerve with variations in the level of the respiratory generator activity evoked by a short (up to 1 min) asphyxia were investigated in experiments on anesthetized and paralyzed rabbits using Wall's method. Antidromic responses decreased up to 5-20% of the control level during activation of the respiratory generator with an increase in frequency and amplitude of rhythmic discharges in the phrenic nerve evoked by a short asphyxia. It is supposed that the primary afferent polarization depends not only on the level of afferent inflow but also on the activity of the central respiratory generator. PMID:7442870

Baev, K V; Shapovalov, A V; Preobrazhenski?, N N; Esipenko, V B

1980-01-01

252

Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury  

Science.gov (United States)

Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (?)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/?)-, (+)-, or (?)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/?)- or (?)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies.

Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

2013-01-01

253

Neuroprotective activity of thioctic acid in central nervous system lesions consequent to peripheral nerve injury.  

Science.gov (United States)

Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (-)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/-)-, (+)-, or (-)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/-)- or (-)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

Tomassoni, Daniele; Amenta, Francesco; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Nwankwo, Innocent E; Pacini, Alessandra; Tayebati, Seyed Khosrow

2013-01-01

254

Liquiritin potentiate neurite outgrowth induced by nerve growth factor in PC12 cells.  

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Neurite outgrowth and neuronal differentiation play a crucial role in the development of the nervous system. Understanding of neurotrophins induced neurite outgrowth was important to develop therapeutic strategy for axon regeneration in neurodegenerative diseases as well as after various nerve injuries. It has been reported that extension of neurite and differentiation of sympathetic neuron-like phenotype was modulated by nerve growth factor (NGF) in PC12 cells. In this study, NGF mediated neurite outgrowth was investigated in PC12 cells after liquiritin exposure. Liquiritin is a kind of flavonoids that is extracted from Glycyrrhizae radix, which is frequently used to treat injury or swelling for its life-enhancing properties as well as detoxification in traditional Oriental medicine. The result showed that liquiritin significantly promotes the neurite outgrowth stimulated by NGF in PC12 cells in dose dependant manners whereas the liquiritin alone did not induce neurite outgrowth. Oligo microarray and RT-PCR analysis further clarified that the neurotrophic effect of liquiritin was related to the overexpression of neural related genes such as neurogenin 3, neurofibromatosis 1, notch gene homolog 2, neuromedin U receptor 2 and neurotrophin 5. Thus, liquiritin may be a good candidate for treatment of various neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. PMID:19789989

Chen, Zheng-Ai; Wang, Jun-Long; Liu, Rui-Ting; Ren, Jian-Ping; Wen, Li-Qing; Chen, Xiao-Juan; Bian, Guang-Xing

2009-07-01

255

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

256

Activation of the phospholipase C signaling pathway in nerve growth factor-treated neurons by carbon nanotubes.  

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Low concentrations of carbon nanotubes (CNTs) promoted the number of nerve growth factor (NGF)-treated neurons with neurite outgrowth by activating extracellular signal-regulated kinase (ERK), even when MEK inhibitor was added to the neuron culture medium. We speculated that CNTs may activate ERK through the phospholipase C (PLC) signaling pathway independent of the Ras/Raf/MEK cascade involved in the ERK signaling pathway. CNTs enhanced phosphorylation of PLC-?1 in NGF-treated neurons but failed to increase the number and length of neurites of NGF-treated neurons with neurite outgrowth when a PLC inhibitor, an inositol triphosphate receptor (IP3R) inhibitor, or an inhibitor of protein kinase C (PKC) in the PLC signaling pathway were added to the neuron culture medium. Furthermore, intracellular Ca(++) levels of cells treated with CNTs+NGF were higher than those of cells treated with NGF alone. Although the combination of CNTs and NGF increased the concentration of phosphorylated ERK (p-ERK) in MEK inhibitor-treated neurons, CNTs did not induce phosphorylation of ERK in PLC inhibitor-treated neurons. These data suggest that PKC in the PLC signaling pathway may activate ERK independent of the Ras/Raf/MEK cascade. In summary, we identified a role of PLC signaling in mediating neurite outgrowth of NGF-treated neurons in the presence of CNTs. PMID:23669261

Matsumoto, Kotaro; Shimizu, Norio

2013-08-01

257

Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling.  

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The growth of a panel of 22 different human tumor, leukemia, and lymphoma cell lines was examined in a human tumor cloning assay in agar or methylcellulose and a tritiated thymidine uptake assay. The cultures were performed in the absence or presence of increasing concentrations (0.5-500 ng/ml) of nerve growth factor (NGF). The growth of 17 of the 22 cell lines was not significantly and reproducibly affected by NGF. There was minor (1.2-fold) but reproducible stimulation of clonal growth in one glioblastoma cell line (86-HG-39) by NGF, but in this cell line NGF induced no growth modulation in a tritiated thymidine uptake assay. However, clonal growth of another glioblastoma cell line (87-HG-31) and all three lung cancer cell lines tested (HTB 119, HTB 120, CCL 185) could be stimulated up to 3-fold by NGF with a dose-response relationship for the growth factor. Growth stimulation by NGF could be completely reversed by neutralizing anti-NGF antibody and by the tyrosine kinase inhibitor genistein. Evaluation of secondary plating efficiency revealed the stimulation of colony formation as representing self-renewal and not terminal differentiation. Reverse transcriptase-PCR experiments in the five responding cell lines showed expression of both low-affinity NGF receptor (glycoprotein 75) and c-trk transcripts on the mRNA level. Of the five responding cell lines, only 86-HG-39, the cell line with the lowest responsiveness, revealed low-affinity NGF receptor on the protein level; the other four cell lines with high responsiveness, including the three lung cancer cell lines, expressed no low-affinity NGF receptor as shown by fluorescence-activated cell sorter analysis and immunoprecipitation using the ME 20.4 antibody. Immunoprecipitation using anti-trk antibodies was negative in all five responding cell lines. However, binding studies with iodinated NGF showed only low-affinity binding on the 86-HG-39 cell line and only high-affinity binding on the high-responder cell lines CCL 185 and 87-HG-31. In summary, our data suggest that NGF can be operative in stimulation of clonal growth of malignant tumor cells. High-affinity but not low-affinity binding sites mediate signal transduction for clonal growth and signaling involves tyrosine kinase activity. PMID:7538048

Oelmann, E; Sreter, L; Schuller, I; Serve, H; Koenigsmann, M; Wiedenmann, B; Oberberg, D; Reufi, B; Thiel, E; Berdel, W E

1995-05-15

258

Structural insights into the dual activities of the nerve agent degrading organophosphate anhydrolase/prolidase.  

Science.gov (United States)

The organophosphate acid anhydrolase (OPAA) is a member of a class of bimetalloenzymes that hydrolyze a variety of toxic acetylcholinesterase-inhibiting organophosphorus compounds, including fluorine-containing chemical nerve agents. It also belongs to a family of prolidases, with significant activity against various Xaa-Pro dipeptides. Here we report the X-ray structure determination of the native OPAA (58 kDa mass) from Alteromonas sp. strain JD6.5 and its cocrystal with the inhibitor mipafox [N,N'-diisopropyldiamidofluorophosphate (DDFP)], a close analogue of the nerve agent organophosphate substrate diisopropyl fluorophosphate (DFP). The OPAA structure is composed of two domains, amino and carboxy domains, with the latter exhibiting a "pita bread" architecture and harboring the active site with the binuclear Mn(2+) ions. The native OPAA structure revealed unexpectedly the presence of a well-defined nonproteinaceous density in the active site whose identity could not be definitively established but is suggestive of a bound glycolate, which is isosteric with a glycine (Xaa) product. All three glycolate oxygens coordinate the two Mn(2+) atoms. DDFP or more likely its hydrolysis product, N,N'-diisopropyldiamidophosphate (DDP), is present in the cocrystal structure and bound by coordinating the binuclear metals and forming hydrogen bonds and nonpolar interactions with active site residues. An unusual common feature of the binding of the two ligands is the involvement of only one oxygen atom of the glycolate carboxylate and the product DDP tetrahedral phosphate in bridging the two Mn(2+) ions. Both structures provide new understanding of ligand recognition and the prolidase and organophosphorus hydrolase catalytic activities of OPAA. PMID:20000741

Vyas, Nand K; Nickitenko, Alexei; Rastogi, Vipin K; Shah, Saumil S; Quiocho, Florante A

2010-01-26

259

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

International Nuclear Information System (INIS)

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

2007-03-01

260

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

Science.gov (United States)

Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crude homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC(50) of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds. PMID:17207828

Moretto, A; Nicolli, A; Lotti, M

2007-03-01

 
 
 
 
261

Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells.  

Science.gov (United States)

Bone marrow stromal cells (MSCs) are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. We now demonstrate that MSCs can be induced to differentiate into cells with Schwann cell characteristics, capable of eliciting peripheral nervous system regeneration in adult rats. MSCs treated with beta-mercaptoethanol followed by retinoic acid and cultured in the presence of forskolin, basic-FGF, PDGF and heregulin, changed morphologically into cells resembling primary cultured Schwann cells and expressing p75, S-100, GFAP and O4. The MSCs were genetically engineered by transduction with retrovirus encoding green fluorescent protein (GFP), and then differentiated by treatment with factors described above. They were transplanted into the cut ends of sciatic nerves, which then responded with vigorous nerve fibre regeneration within 3 weeks of the operation. Myelination of regenerated fibers by GFP-expressing MSCs was recognized using confocal and immunoelectron microscopy. The results suggest that MSCs are able to differentiate into myelinating cells, capable of supporting nerve fibre re-growth, and they can therefore be applied to induce nerve regeneration. PMID:11860471

Dezawa, M; Takahashi, I; Esaki, M; Takano, M; Sawada, H

2001-12-01

262

Concentration of extracellular L-glutamate released from cultured nerve cells measured with a small-volume online sensor.  

Science.gov (United States)

An online sensor with a low detection limit for L-glutamate was developed in order to monitor the change in the extracellular L-glutamate concentration as a result of stimulated release from cultured nerve cells. The sensor consisted of a microdialysis (MD) probe fixed at the manipulator, a small-volume L-glutamate oxidase enzymatic reactor (0.75 mm i.d. and 2.5 cm long), and an electrochemical detector in a thin-layer radial flow cell with an active volume of 70-340 nL. Glassy carbon bulk or carbon film ring-disk electrodes were used as detectors by modifying them with Os poly(vinylpyridine) mediator containing horseradish peroxidase. The overall efficiency of L-glutamate detection with the sensor is 94% under optimum conditions, due to an efficient enzymatic reaction in the reactor and a high conversion efficiency in the radial flow cell. As a result, we achieved a sensitivity of 24.3 nA/muM and a detection limit of 7.2 nM (S/N = 3). The effect of interferents such as L-ascorbic acid can be minimized effectively by applying a low potential to the electrode for hydrogen peroxide detection (O mV) and via the ring-disk electrode geometry by using the disk for preoxidation. In the in vitro experiment, an MD probe for sampling was connected to a manipulator that controls distance between the probe and the stimulated cells. The cells were stimulated by KCl in a glass capillary or electrically with microarray film electrodes fabricated on a substrate. By using the sensor, we can monitor L-glutamate concentration changes at the submicromolar level caused by KCl stimulation of a single nerve cell and micromolar L-glutamate concentration increases caused by electrical stimulation of a brain slice. An increase in L-glutamate concentration can also be measured by positioning the probe near the cell that is connected synaptically to the stimulated cell. PMID:8686911

Niwa, O; Torimitsu, K; Morita, M; Osborne, P; Yamamoto, K

1996-06-01

263

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

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

Dwaipayan Sen

2013-10-01

264

SOD1(G93A) transgenic mouse CD4(+) T cells mediate neuroprotection after facial nerve axotomy when removed from a suppressive peripheral microenvironment.  

Science.gov (United States)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving motoneuron (MN) axonal withdrawal and cell death. Previously, we established that facial MN (FMN) survival levels in the SOD1(G93A) transgenic mouse model of ALS are reduced and nerve regeneration is delayed, similar to immunodeficient RAG2(-/-) mice, after facial nerve axotomy. The objective of this study was to examine the functionality of SOD1(G93A) splenic microenvironment, focusing on CD4(+) T cells, with regard to defects in immune-mediated neuroprotection of injured MN. We utilized the RAG2(-/-) and SOD1(G93A) mouse models, along with the facial nerve axotomy paradigm and a variety of cellular adoptive transfers, to assess immune-mediated neuroprotection of FMN survival levels. We determined that adoptively transferred SOD1(G93A) unfractionated splenocytes into RAG2(-/-) mice were unable to support FMN survival after axotomy, but that adoptive transfer of isolated SOD1(G93A) CD4(+) T cells could. Although WT unfractionated splenocytes adoptively transferred into SOD1(G93A) mice were able to maintain FMN survival levels, WT CD4(+) T cells alone could not. Importantly, these results suggest that SOD1(G93A) CD4(+) T cells retain neuroprotective functionality when removed from a dysfunctional SOD1(G93A) peripheral splenic microenvironment. These results also indicate that the SOD1(G93A) central nervous system microenvironment is able to re-activate CD4(+) T cells for immune-mediated neuroprotection when a permissive peripheral microenvironment exists. We hypothesize that a suppressive SOD1(G93A) peripheral splenic microenvironment may compromise neuroprotective CD4(+) T cell activation and/or differentiation, which, in turn, results in impaired immune-mediated neuroprotection for MN survival after peripheral axotomy in SOD1(G93A) mice. PMID:24911596

Mesnard-Hoaglin, Nichole A; Xin, Junping; Haulcomb, Melissa M; Batka, Richard J; Sanders, Virginia M; Jones, Kathryn J

2014-08-01

265

Improvement of Sciatic Nerve Regeneration Using Laminin-Binding Human NGF-?  

Science.gov (United States)

Background Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-? could target to nerve cells and improve nerve regeneration. Methods Laminin-binding assay and sustained release assay of NGF-? fused with NtA (LBD-NGF) from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested. Findings LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages. Conclusion Fused with NtA, NGF-? could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries.

Sun, Wenjie; Sun, Changkai; Zhao, Hui; Lin, Hang; Han, Qianqian; Wang, Jingyu; Ma, Hui; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu

2009-01-01

266

Role of potassium channels in the frequency-dependent activity of regenerating nerves.  

Science.gov (United States)

After a peripheral nerve injury, ion channel organization and the electrical properties of nerve fibers drastically change during the regeneration process. The present study was designed to compare the frequency-dependent characteristics of regenerating nerves in the presence of 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The results showed that increasing the stimulus frequency produced a greater impulse blockade (frequency-dependent block--FDB) and distinct hyperpolarizing afterpotentials (HAPs) in regenerating nerves. In particular, regenerating sciatic nerves 15 days post-crush (dpc) were more sensitive to the frequency-dependent stimulations than 38-dpc and intact nerves in the presence or absence of drugs. The frequency-dependent effects of TEA on the compound action potentials (CAPs) appeared when TEA was applied to 4-AP-treated nerves. This shows that TEA-sensitive channels may not be masked by the myelin. 4-AP was here found to have more pronounced frequency-dependent effects on regenerating nerves than on intact nerves. Delayed depolarization (in 38-dpc: 22.6 +/- 1.3 mV and 47.52 +/- 3.63 ms, in intact: 12.0 +/- 1.9 mV and 88.51 +/- 4.72 ms) elicited by 4-AP resulted in an increase in FDBs and HAP amplitudes. These results suggest that 4-AP-sensitive channels may play important roles in frequency-dependent nerve conduction. Consequently, regenerating or myelin damaged nerves are more sensitive to repetitive firing with or without drug. An understanding of the frequency-dependent properties of regenerating nerves may be of value in the treatment of the nerve diseases. PMID:15452364

Mert, Tufan; Gunay, Ismail; Daglioglu, Yusuf Kenan

2004-11-01

267

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

268

s-Methyl cysteine enhanced survival of nerve growth factor differentiated PC12 cells under hypoxic conditions.  

Science.gov (United States)

A nerve growth factor-differentiated PC12 cell line was used to investigate the protective effects of s-methyl cysteine (SMC) at 1, 2, 4, and 8 ?M under oxygen-glucose deprivation (OGD) conditions. OGD decreased the cell viability. However, SMC pre-treatments at 2, 4 and 8 ?M improved the cell viability, decreased cleaved caspase-3 and Bax expression, and reserved Bcl-2 expression. Furthermore, SMC maintained the mitochondrial membrane potential, lowered the intracellular Ca(2+) concentration and DNA fragmentation, and decreased the activity and expression of caspase-3 and caspase-8. OGD increased the reactive oxygen species (ROS) and 3-nitrotyrosine production, decreased glutathione peroxide (GPX) and glutathione reductase (GR) activities and the expression, enhanced nitric oxide synthase (NOS) activity and inducible NOS (iNOS) expression. SMC pre-treatments at 2, 4 and 8 ?M lowered the ROS and 3-nitrotyrosine formation, maintained GPX and GR activities and expression, and decreased NOS activity and iNOS expression. OGD up-regulated hypoxia-inducible factor (HIF)-1?, nuclear transcription factor kappa (NF-?) B p50, NF-?B p65 and p-p38 expression. SMC pre-treatments at 1-8 ?M lowered HIF-1? expression and decreased p38 phosphorylation. SMC at 2, 4 and 8 ?M suppressed the protein expression of NF-?B p50 and NF-?B p65. When YC-1 (HIF-1? inhibitor), pyrrolidine dithiocarbamate (NF-?B inhibitor) or SB203580 (p38MAPK inhibitor) were used to block the activation of HIF-1?, NF-?B and p38, SMC pre-treatments did not affect the protein expression of HIF-1?, NF-?B and p-p38. These results indicated that SMC was a potent neuro-protective agent. PMID:24710107

Liu, Chun-Lin; Hsia, Te-Chun; Yin, Mei-Chin

2014-06-28

269

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

Scientific Electronic Library Online (English)

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

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

270

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

Scientific Electronic Library Online (English)

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

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

2014-05-30

271

Axons regulate the expression of Shaker-like potassium channel genes in Schwann cells in peripheral nerve.  

Science.gov (United States)

We examined potassium channel gene expression of two members of the Shaker subfamily, MK1 and MK2, in sciatic nerves from rats and mice. In Northern blot analysis, MK1 and MK2 probes detected single transcripts of approximately 8 kb and approximately 9.5 kb, respectively, in sciatic nerve and brain from both species. Polymerase chain reaction amplification of a cDNA library of cultured rat Schwann cells using MK1- and MK2- specific primers produced DNA fragments that were highly homologous to MK1 and MK2. To determine whether these channel genes were axonally regulated, we performed Northern blot analysis of developing, permanently transected, and crushed rat sciatic nerves. The mRNA levels for both MK1 and MK2 increased from P1 to P15 and then declined modestly. Permanent nerve transection in adult animals resulted in a dramatic and permanent reduction in the mRNA levels for both MK1 and MK2, whereas normal levels of MK1 and MK2 were restored when regeneration was allowed to occur following crush injury. In all cases, MK1 and MK2 mRNA levels paralleled that of the myelin gene P0. Elevating the cAMP in cultured Schwann cells by forskolin, which mimics axonal contact but not myelination, did not induce detectable levels of MK1 and MK2 mRNA by Northern blot analysis. Further, the level of MK1 mRNA in the vagus nerve, which contains relatively fewer myelinating Schwann cells and relatively more non-myelinating Schwann cells than the sciatic nerve, is reduced relative to the sciatic nerve. In conclusion, we have identified two Shaker-like potassium channel genes in sciatic nerves whose expressions are regulated by axons. We suggest that MK1 and MK2 mRNA are expressed in high levels only in myelinating Schwann cells and that these Shaker-like potassium channel genes have specialized roles in these cells. PMID:7843783

Chiu, S Y; Scherer, S S; Blonski, M; Kang, S S; Messing, A

1994-09-01

272

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2002-01-01

273

The apolipoprotein A-I gene is actively expressed in the rapidly myelinating avian peripheral nerve  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The expression of the apolipoprotein A-I (apo A-I) gene was investigated in the myelinating sciatic nerve. Hybridization analysis with an apo A-I cDNA probe obtained from a cDNA library of mRNA isolated from rapidly myelinating chick sciatic nerve indicated that apo A-I coding transcripts increase during development in the chick sciatic nerve in parallel with the increase of myelin lamellae. Substantial apo A-I-like immunoreactivity in chick sciatic nerve homogenates was detected by Western b...

1989-01-01

274

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

International Nuclear Information System (INIS)

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

1982-01-01

275

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

LENUS (Irish Health Repository)

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

Griffin, K M

2011-08-01

276

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

International Nuclear Information System (INIS)

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

2011-08-01

277

Therapeutic effect of myogenic cells modified to express neurotrophic factors in a rat model of sciatic nerve injury.  

Science.gov (United States)

Sciatic nerve injury may cause neurological deficits, particularly muscle weakness. Previous studies have shown that administration of neurotrophic factors (NTFs), naturally occurring proteins that support the development and survival of neurons, partially protected the damaged motor neuron in the injured sciatic nerve. In the current study, we have examined whether the administration of various combinations of transfected muscle progenitor cells (MPCs) populations, each expressing a single NTF (BDNF, GDNF, IGF-1 or VEGF) or conditioned media of such culture are capable of rescuing motor neurons in culture or in vivo. We have found that the mixture of conditioned media collected from cultured myogenic cells (MPCs- MIX(+)) alleviated the toxic effect of exposure of the motor neuron cell line NSC34 to hypoxic environment. Furthermore, NTFs secreting cells transplantation, protected motor neurons in a unilateral rat sciatic nerve injury model: One day after the crush, rats underwent transplantation at the lesion site with rat myogenic cells expressing one of the four NTFs; a mixture of cells expressing all four NTFs (MPCs- MIX(+)), MPCs-GFP or PBS. We found that in rats injected with MPCs- MIX(+) the motor function was markedly preserved, compared to groups injected with cells secreting a single NTF, GFP or PBS. Transplantation of the MPCs- MIX(+) significantly inhibited the degeneration of the neuromuscular junctions and enhanced the survival of the myelinated motor axons. The injection of MPCs- MIX(+) preserved the compound muscle action potential (CMAP) as was demonstrated by motor nerve conduction studies. Our findings suggest that MPCs induced to secrete several NTFs can synergistically alleviate symptoms of sciatic nerve injury and perhaps other motor neuron disorders.. PMID:24693189

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

2012-01-01

278

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device, capable of local delivery of NGF. The clinical device, named NsG0202, houses an NGF-secreting cell line (NGC-0295), which is derived from a human retinal pigment epithelial (RPE) cell line, stably geneti...

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

2010-01-01

279

Nerve growth factor induces neuron-like differentiation of an insulin-secreting pancreatic beta cell line.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Nerve growth factor (NGF) is the best understood of a class of trophic proteins that are important for the survival of neurons and the elaboration of their characteristic processes. Here we demonstrate that RINm5F, a rat insulinoma cell line representing an early stage in pancreatic beta cell differentiation, expresses both the Trk and p75 NGF receptors and responds to NGF by extending neurite-like (neurofilament-containing) processes. NGF treatment of RINm5F cells also induces the expression...

Polak, M.; Scharfmann, R.; Seilheimer, B.; Eisenbarth, G.; Dressler, D.; Verma, I. M.; Potter, H.

1993-01-01

280

Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers.  

Science.gov (United States)

In an axonal variant of Guillain-Barré syndrome (GBS) associated with Campylobacter jejuni (C. jejuni) enteritis, the mechanism underlying axonal damage is obscure. We purified and characterized a DNA-binding protein from starved cells derived from C. jejuni (C-Dps). This C-Dps protein has significant homology with Helicobacter pylori neutrophil-activating protein (HP-NAP), which is chemotactic for human neutrophils through binding to sulfatide. Because sulfatide is essential for paranodal junction formation and for the maintenance of ion channels on myelinated axons, we examined the in vivo effects of C-Dps. First, we found that C-Dps specifically binds to sulfatide by ELISA and immunostaining of thin-layer chromatograms loaded with various glycolipids. Double immunostaining of peripheral nerves exposed to C-Dps with anti-sulfatide antibody and anti-C-Dps antibody revealed co-localization of them. When C-Dps was injected into rat sciatic nerves, it densely bound to the outermost parts of the myelin sheath and nodes of Ranvier. Injection of C-Dps rapidly induced paranodal myelin detachment and axonal degeneration; this was not seen following injection of PBS or heat-denatured C-Dps. Electron microscopically, C-Dps-injected nerves showed vesiculation of the myelin sheath at the nodes of Ranvier. Nerve conduction studies disclosed a significant reduction in compound muscle action potential amplitudes in C-Dps-injected nerves compared with pre-injection values, but not in PBS-, heat-denatured C-Dps-, or BSA-injected nerves. However, C-Dps did not directly affect Na(+) currents in dissociated hippocampal neurons. Finally, when C-Dps was intrathecally infused into rats, it was deposited in a scattered pattern in the cauda equina, especially in the outer part of the myelin sheath and the nodal region. In C-Dps-infused rats, but not in BSA-infused ones, a decrease in the number of sodium channels, vesiculation of the myelin sheath, axonal degeneration and infiltration of Iba-1-positive macrophages were observed. Thus, we consider that C-Dps damages myelinated nerve fibers, possibly through interference with paranodal sulfatide function, and may contribute to the axonal pathology seen in C. jejuni-related GBS. PMID:19880143

Piao, Hua; Minohara, Motozumi; Kawamura, Nobutoshi; Li, Wei; Mizunoe, Yoshimitsu; Umehara, Fujio; Goto, Yoshinobu; Kusunoki, Susumu; Matsushita, Takuya; Ikenaka, Kazuhiro; Maejima, Takashi; Nabekura, Jun-ichi; Yamasaki, Ryo; Kira, Jun-ichi

2010-01-15

 
 
 
 
281

BioPEGylation of polyhydroxybutyrate promotes nerve cell health and migration.  

Science.gov (United States)

This study reports on the superior suitability of Polyhydroxybutyrate-polyethylene glycol hybrid polymers biosynthesised by Cupriavidus necator over PHB as biomaterials for tissue engineering. Incorporation of PEG106 (DEG) during PHB biosynthesis reduced crystallinity, molecular weight, and hydrophobicity while improving mechanical properties. In vitro olfactory ensheathing cell (OEC) proliferation was enhanced by cultivation on PHB-b-DEG films. Cultivation on PHB and PHB-b-DEG films showed no cytotoxic responses and cell viability and membrane integrity was sustained. PHB-b-DEG films promoted OECs entering into the DNA replication (S) phase and mitotic (G2-M) phase during the cell growth cycle and apoptosis was low. This study also confirmed an association between the level of neurite-outgrowth inhibitory protein (Nogo) and receptor pair Ig-like receptor B (PirB) expression and cell proliferation, both being down-regulated in cells grown on hybrid films when compared with PHB and asynchronous growth. Thus, DEG-terminated PHB-based biomaterials have great potential as biological scaffolds supporting nerve repair. PMID:24299034

Chan, Rodman T H; Russell, Robert A; Marçal, Helder; Lee, Terry H; Holden, Peter J; Foster, L John R

2014-01-13

282

Altered nerve growth factor in fibroblasts from patients with familial dysautonomia.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Nerve growth factor was measured in cultured human skin fibroblasts from controls and from patients with familial dysautonomia and dystonia musculoram deformans. Cells from these sources grown over a range of cell densities contained similar levels of beta-nerve growth factor as measured by radioimmunoassay. Results of bioassay demonstrated that the nerve growth factor from dysautonomic cells was only approximately 10% as active per ng of immunoreactive protein as that from control and dyston...

1980-01-01

283

Percutaneous recording of muscle nerve sympathetic activity during propofol, nitrous oxide, and isoflurane anesthesia in humans.  

Science.gov (United States)

The effects of propofol, nitrous oxide, and/or isoflurane on efferent activity of sympathetic muscle nerve fibers (MSA) were studied using percutaneous microneurographic recordings from the peroneal nerve. Eight ASA Physical Status 1 patients (30-70 yr of age) scheduled for otorhinolaryngeal surgery entered the study. The effects of propofol (2-2.5 mg.kg-1.min-1) induction, tracheal intubation, and maintenance of anesthesia with isoflurane (0.3%, 0.6%, and 1.2% end-tidal concentrations) and/or 70% nitrous oxide were studied with respect to MSA, arterial blood pressure, heart rate, and indices of skin blood flow (laser doppler photometry and finger pulse plethysmography). Induction of anesthesia with propofol decreased MSA to 34 +/- 2% (mean +/- SEM) (P less than 0.05), and subsequent tracheal intubation increased MSA rapidly to 151 +/- 23% (P less than 0.05) of the control level. Isoflurane administration both with and without nitrous oxide led to a decrease of MSA (P less than 0.05). However, during nitrous oxide/isoflurane anesthesia (1.0 MAC) MSA was 76 +/- 38% higher than when isoflurane was used alone, although this implied a decrease in anesthetic depth to 0.5 MAC. This indicates that nitrous oxide and isoflurane have opposite effects on sympathetic outflow. During undisturbed propofol, nitrous oxide, and/or isoflurane administration (up to 1.0 MAC), MSA retained its normal pulse synchronous pattern, indicating that modulation of sympathetic outflow from arterial baroreceptors was still present. Skin blood flow increased sevenfold to tenfold in association with propofol induction (P less than 0.05) and was maintained at an 11- to 19-fold increase during nitrous oxide and/or isoflurane anesthesia, without any difference between the two anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2360736

Sellgren, J; Pontén, J; Wallin, B G

1990-07-01

284

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2011-01-01

285

Squamous cell carcinoma and suspect peripheral nerve sheath tumor in a 10-year-old Paint horse  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A round mass 4 cm in diameter was present on the proximal rostro-lateral border of the right pinna of a 10-year-old, gelded, Paint horse. A preliminary histopathological diagnosis of a potential squamous cell carcinoma and peripheral nerve sheath tumor was made, and the lesion was resected at the base of the lateral edge of the ear.

2009-01-01

286

Structural requirement of TAG-1 for retinal ganglion cell axons and myelin in the mouse optic nerve.  

Science.gov (United States)

White matter axons organize into fascicles that grow over long distances and traverse very diverse environments. The molecular mechanisms preserving this structure of white matter axonal tracts are not well known. Here, we used the optic nerve as a model and investigated the role of TAG-1, a cell adhesion molecule expressed by retinal axons. TAG-1 was first expressed in the embryonic retinal ganglion cells (RGCs) and later in the postnatal myelin-forming cells in the optic nerve. We describe the consequences of genetic loss of Tag-1 on the developing and adult retinogeniculate tract. Tag-1-null embryos display anomalies in the caliber of RGC axons, associated with an abnormal organization of the astroglial network in the optic nerve. The contralateral projections in the lateral geniculate nucleus are expanded postnatally. In the adult, Tag-1-null mice show a loss of RGC axons, with persistent abnormalities of axonal caliber and additional cytoskeleton and myelination defects. Therefore, TAG-1 is an essential regulator of the structure of RGC axons and their surrounding glial cells in the optic nerve. PMID:18650339

Chatzopoulou, Elli; Miguez, Andrés; Savvaki, Maria; Levasseur, Grégoire; Muzerelle, Aude; Muriel, Marie-Paule; Goureau, Olivier; Watanabe, Kazutada; Goutebroze, Laurence; Gaspar, Patricia; Zalc, Bernard; Karagogeos, Domna; Thomas, Jean-Léon

2008-07-23

287

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

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

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

2009-06-03

288

Increases in muscle sympathetic nerve activity, heart rate, respiration and skin blood flow during passive viewing of exercise  

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Full Text Available The cardiovascular and respiratory effects of exercise have been widely studied, as have the autonomic effects of imagined and observed exercise. However, the effects of observed exercise in the first person have not been documented, nor have direct recordings of muscle sympathetic nerve activity (MSNA been obtained during observed or imagined exercise. The aim of the current study was to measure blood pressure, heart rate, respiration, skin blood flow, sweat release and muscle sympathetic nerve activity (via microelectrodes inserted into the common peroneal nerve, during observation of exercise from the first person point of view. It was hypothesised that the moving stimuli would produce robust compensatory increases in the above-mentioned parameters as effectively as those generated by mental imagery and - to a lesser extent - actual exercise. Nine subjects watched a first-person running video, allowing them to view the action from the perspective of the runner rather than viewing someone else perform the exercise. On average, statistically significant increases from baseline during the running phase were seen in heart rate, respiratory rate, skin blood flow and burst amplitude of muscle sympathetic nerve activity. These results suggest that observation of exercise in the first person is a strong enough stimulus to evoke “physiologically appropriate” autonomic responses that have a purely psychogenic origin.

RachaelBrown

2013-06-01

289

Production of nerve growth-stimulating factor(s) from chick embryo heart cells. Use of Cytodex 3 microcarriers and serum-free media.  

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Medium conditioned by embryonic chick heart cells is known to support extensive neurite outgrowth from autonomic and sensory neurons. In the present report we describe the use of microcarrier cell culture with serum-free media to scale up the production of the nerve growth-stimulating factors. A growth medium composed of DME /F10 supplemented with insulin, transferrin, human serum albumin and fibronectin in combination with a low molecular weight (MW) fraction of fetal calf serum (FCS) or a mixture of FGF, dexamethasone, calmodulin and thrombin supported the heart cell proliferation at a rate similar to that of medium with 10% FCS. Furthermore, the level of successively accumulated nerve growth activity measured in a bioassay with sympathetic ganglia proved to be nearly equivalent to what was obtained when cells were grown in medium containing serum. The results confirm the potential of microcarrier cell culture in serum-free media for the production and subsequent recovery of a specific cell product. PMID:6723797

Norrgren, G; Ebendal, T; Wikström, H

1984-06-01

290

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

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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.

Dahlin Lars B

2008-09-01

291

Peripheral chemoreflex sensitivity and sympathetic nerve activity are normal in apnea divers during training season.  

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Apnea divers are exposed to repeated massive arterial oxygen desaturation, which could perturb chemoreflexes. An earlier study suggested that peripheral chemoreflex regulation of sympathetic vasomotor tone and ventilation may have recovered 4 or more weeks into the off season. Therefore, we tested the hypothesis that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is present during the training season. We determined ventilation, heart rate, blood pressure, cardiac stroke volume, and muscle sympathetic nerve activity (MSNA) during isocapnic hypoxia in 10 breath hold divers and 11 matched control subjects. The study was carried out at the end of the season of intense apnea trainings. Baseline MSNA frequency was 30+/-4bursts/min in control subjects and 25+/-4bursts/min in breath hold divers (P=0.053). During hypoxia burst frequency and total sympathetic activity increased similarly in both groups. Sympathetic activity normalized during the 30-minute recovery. Hypoxia-induced stimulation of minute ventilation was similar in both groups, although in divers it was maintained by higher tidal volumes and lower breathing frequency compared with control subjects. In both groups, hypoxia increased heart rate and cardiac output whereas total peripheral resistance decreased. Blood pressure remained unchanged. We conclude that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is paradoxically preserved in apnea divers, both, during the off and during the training season. The observation suggests that repeated arterial oxygen desaturation may not be sufficient explaining sympathetic reflex abnormalities similar to those in obstructive sleep apnea patients. PMID:19926535

Breskovic, Toni; Ivancev, Vladimir; Banic, Ivana; Jordan, Jens; Dujic, Zeljko

2010-04-19

292

Characteristics of muscle nerve sympathetic activity during general anaesthesia in humans.  

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General anaesthesia influences the cardiovascular system at different levels. To increase our knowledge of how sympathetic outflow is affected by anaesthetic interventions, we used direct microelectrode recordings of muscle sympathetic activity (MSA) in the peroneal nerve in 18 patients scheduled for ENT-surgery. During induction of anaesthesia (propofol 2.1 mg/kg or methohexitone 1.4 mg/kg), all patients showed reductions in MSA (from 41 +/- 4 to 20 +/- 4 bursts/min). With endotracheal intubation there was a sudden increase of activity and in several patients the normal pulse-synchrony of MSA was lost temporarily. Maintenance of anaesthesia with nitrous oxide (n = 12) increased MSA and methohexitone (n = 2), propofol (n = 3) and isoflurane (n = 8) decreased MSA, while the effect of halothane (n = 3) varied. Baroreflex mechanisms were still operative but seemed to be depressed in relation to anaesthetic agent and depth. Laryngeal and surgical stimuli caused increases in MSA and blood pressure, lasting several minutes after the stimulation. It is concluded that the strength of MSA is profoundly influenced by the choice of anaesthetic agent. A suppression of activity is more common than an increase. Qualitatively, several sympathetic reflexes operate in a similar way during light anaesthesia as in awake subjects, but are depressed or absent during deep anaesthesia. PMID:1595340

Sellgren, J; Pontén, J; Wallin, B G

1992-05-01

293

Substances originating from the optic nerve of neonatal rabbit induce regeneration-associated response in the injured optic nerve of adult rabbit.  

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We have recently shown that cell bodies of an injured optic nerve of adult rabbit can be induced to express regeneration-associated response by external signals derived from nonneuronal cells of regenerating nerves of lower vertebrates. In this study it is shown that even substances derived from a nonregenerating mammalian system also can trigger such a regenerative response. Thus, substances derived from intact nerves of neonatal rabbits and of adult rabbits, to a lesser extent, were active ...

Hadani, M.; Harel, A.; Solomon, A.; Belkin, M.; Lavie, V.; Schwartz, M.

1984-01-01

294

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

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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

2008-01-01

295

Use of dexamethasone with TTX block of nerve conduction shows that muscle membrane properties are fully controlled by evoked activity.  

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This paper provides further evidence that motorneurons control extrajunctional properties of skeletal muscles through the activity evoked in the muscle fibres. The experiments compare the amount of action potential resistance to tetrodotoxin (TTX resistance) in denervated soleus muscle with that in soleus whose nerve was crushed and then allowed to regenerate in the presence of a block of the sciatic impulse conduction. Measurements were taken after about 2-3 weeks to allow full reinnervation and recovery of trophic regulation by the nerve. Blocking sciatic impulse conduction with TTX solutions containing low doses of the anti-inflammatory drug dexamethasone induced values of extrajunctional TTX resistance identical to those caused by denervation. In contrast lower levels of TTX resistance were obtained with dexamethasone-free solutions or when the drug was administered through the systemic path rather than topically applied to the nerve. These results indicate that physiological neural regulatory signals other than activity do not participate to the regulation of extrajunctional properties of skeletal muscles. Furthermore the low levels of TTX resistance measured with dexamethasone-free blocks confirm our previous experiments indicating that reported differences between denervation and pure inactivity are attributable to incomplete suppression of nerve impulse conduction. PMID:9372225

Pasino, E; Buffelli, M; Busetto, G; Cangiano, A

1997-10-01

296

Dissociation of muscle sympathetic nerve activity and leg vascular resistance in humans  

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We examined the hypothesis that the increase in inactive leg vascular resistance during forearm metaboreflex activation is dissociated from muscle sympathetic nerve activity (MSNA). MSNA (microneurography), femoral artery mean blood velocity (FAMBV, Doppler), mean arterial pressure (MAP), and heart rate (HR) were assessed during fatiguing static handgrip exercise (SHG, 2 min) followed by posthandgrip ischemia (PHI, 2 min). Whereas both MAP and MSNA increase during SHG, the transition from SHG to PHI is characterized by a transient reduction in MAP but sustained elevation in MSNA, facilitating separation of these factors in vivo. Femoral artery vascular resistance (FAVR) was calculated (MAP/MBV). MSNA increased by 59 +/- 20% above baseline during SHG (P < 0.05) and was 58 +/- 18 and 78 +/- 18% above baseline at 10 and 20 s of PHI, respectively (P < 0.05 vs. baseline). Compared with baseline, FAVR increased 51 +/- 22% during SHG (P < 0.0001) but returned to baseline levels during the first 30 s of PHI, reflecting the changes in MAP (P < 0.005) and not MSNA. It was concluded that control of leg muscle vascular resistance is sensitive to changes in arterial pressure and can be dissociated from sympathetic factors.

Shoemaker, J. K.; Herr, M. D.; Sinoway, L. I.

2000-01-01

297

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis.  

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Effective treatment of sepsis remains a significant challenge in intensive care units. During sepsis, there is widespread activation of the sympathetic nervous system, which is thought to have both beneficial and detrimental effects. The sympathoexcitation is thought to be partly due to the developing hypotension, but may also be a response to the inflammatory mediators released. Thus, we investigated whether intracarotid infusion of prostaglandin E2 (PGE2) induced similar cardiovascular changes to those caused by intravenous infusion of Escherichia coli in sheep and whether inhibition of prostaglandin synthesis, with the nonselective cyclooxygenase inhibitor indomethacin, administered at 2 and 8 h after the onset of sepsis, reduced sympathetic nerve activity (SNA), and heart rate (HR). Studies were performed in conscious sheep instrumented to measure mean arterial pressure (MAP), HR, cardiac SNA (CSNA), and renal SNA (RSNA). Intracarotid infusion of PGE2 (50 ng·kg(-1)·min(-1)) increased temperature, CSNA, and HR, but not MAP or RSNA. Sepsis, induced by infusion of E. coli, increased CSNA, but caused an initial, transient inhibition of RSNA. At 2 h of sepsis, indomethacin (1.25 mg/kg bolus) increased MAP and caused reflex decreases in HR and CSNA. After 8 h of sepsis, indomethacin did not alter MAP, but reduced CSNA and HR, without altering baroreflex control. These findings indicate an important role for prostaglandins in mediating the increase in CSNA and HR during the development of hyperdynamic sepsis, whereas prostaglandins do not have a major role in determining the early changes in RSNA. PMID:24789991

Booth, Lindsea C; Ramchandra, Rohit; Calzavacca, Paolo; May, Clive N

2014-07-01

298

Alteration of binding properties and cytoskeletal attachment of nerve growth factor receptors in PC12 cells by wheat germ agglutinin  

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Incubation of PC12 cells preloaded with 125I-nerve growth factor (NGF) reveals rapidly and slowly dissociating binding components indicative of a heterogeneous population of receptors. If the cells are previously exposed to wheat germ agglutinin (WGA) for 30 min, NGF now binds to an apparently homogeneous receptor population which exhibit slow dissociation kinetics. Total binding is also reduced by 50%. If WGA is added subsequent to 125I-NGF, total binding is not diminished, but rapidly disso...

1982-01-01

299

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

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

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

2010-03-01

300

Perspectives of employing mesenchymal stem cells from the Wharton's jelly of the umbilical cord for peripheral nerve repair.  

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Mesenchymal stem cells (MSCs) from Wharton's jelly present high plasticity and low immunogenicity, turning them into a desirable form of cell therapy for the injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue. Great concern has been dedicated to the collection, preservation, and transport protocols of the umbilical cord after the parturition to the laboratory in order to obtain samples with higher number of viable MSCs without microbiological contamination. Different biomaterials like chitosan-silicate hybrid, collagen, PLGA90:10, poly(DL-lactide-?-caprolactone), and poly(vinyl alcohol) loaded with electrical conductive materials, associated to MSCs have also been tested in the rat sciatic nerve in axonotmesis and neurotmesis lesions. The in vitro studies of the scaffolds included citocompatibility evaluation of the biomaterials used and cell characterization by imunocytochemistry, karyotype analysis, differentiation capacity into neuroglial-like cells, and flow cytometry. The regeneration process follow-up has been performed by functional analysis and the repaired nerves processed for stereological studies permitted the morphologic regeneration evaluation. The MSCs from Wharton's jelly delivered through tested biomaterials should be regarded a potentially valuable tool to improve clinical outcome especially after trauma to sensory nerves. In addition, these cells represent a noncontroversial source of primitive mesenchymal progenitor cells, which can be harvested after birth, cryogenically stored, thawed, and expanded for therapeutic uses. The importance of a longitudinal study concerning tissue engineering of the peripheral nerve, which includes a multidisciplinary team able to develop biomaterials associated to cell therapies, to perform preclinical trials concerning animal welfare and the appropriate animal model is here enhanced. PMID:24083432

Ribeiro, Jorge; Gartner, Andrea; Pereira, Tiago; Gomes, Raquel; Lopes, Maria Ascensão; Gonçalves, Carolina; Varejão, Artur; Luís, Ana Lúcia; Maurício, Ana Colette

2013-01-01

 
 
 
 
301

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

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

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

2010-07-16

302

Prostaglandin E2 induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves  

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BACKGROUND AND PURPOSE The acute effects of PGE2 on bladder smooth muscle and nerves were examined to determine the origin of PGE2-induced spontaneous rhythmic contractions. EXPERIMENTAL APPROACH Contraction studies, confocal Ca(2+) imaging and electrophysiological recordings in strips of mouse urinary bladder were used to differentiate the effects of PGE(2) on bladder smooth muscle and efferent nerves. KEY RESULTS PGE(2) (50 mu M) increased the tone and caused phasic contractions of detrusor...

Kobayter, S.; Young, J. S.; Brain, K. L.

2012-01-01

303

Frequency-dependent modulation of renal blood flow by renal nerve activity in conscious rabbits.  

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To examine the influence of the various frequency components of renal sympathetic nerve activity (RSNA) on renal blood flow (RBF) dynamics, a Doppler flow probe and renal nerve electrode were implanted on the left renal artery of 10 rabbits. Experiments were performed 4-9 days after surgery. Physiological changes in RSNA were induced by subjecting the rabbits to periods of breathing hypoxic gas mixtures. Signals were sampled at 1 kHz and analyzed by spectral analysis. During moderate hypoxia (arterial PO2 = 44 +/- 1 mmHg), arterial pressure and heart rate did not change, averaged RSNA increased by 90 +/- 7%, and RBF fell by 18 +/- 3%. In a separate group of renal-denervated rabbits (n = 6), no changes in RBF occurred during hypoxia. In intact rabbits, 53 +/- 4% of spectral density power of RSNA was found at the cardiac frequency and the remainder was predominantly coupled to respiration (approximately 0.9 Hz). During moderate hypoxia the amplitude of the RSNA oscillations increased 17 +/- 6 times at the cardiac frequency and 10 +/- 3 times at the respiration-related frequency. Modulation of RBF variability by the fluctuations of RSNA at the cardiac- and respiration-related frequency was, however, small. The normalized transfer gain between RSNA and RBF was approximately 0.1 at > 0.5 Hz. This means that, at > 0.5 Hz, maximally 10% of the amplitude of the RSNA oscillations is transmitted to corresponding RBF fluctuations. These transfer properties did not change during hypoxia. At oscillations of RSNA and RBF were found. In renal-denervated rabbits, 0.3-Hz oscillations in RBF were absent. Thus the renal vasculature was able to follow relatively low-frequency (oscillations in RBF. In contrast, the renal vasculature responded with increased constriction at the high-frequency (> 0.5-Hz) fluctuations of RSNA. These findings suggest that, in conscious rabbits, high-frequency oscillations of RSNA contribute to the vasoconstrictor tone, whereas the lower frequencies of RSNA contribute to the variability of RBF. PMID:9277544

Janssen, B J; Malpas, S C; Burke, S L; Head, G A

1997-08-01

304

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

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

A. M. Durigon

2005-03-01

305

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

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Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 min of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts, -2.9 ± 1.1%; and multiple bursts, -11.0 ± 1.4%; both, P humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts, an effect that was absent for cardiac cycles without MSNA bursts. PMID:23292718

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

2013-03-01

306

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

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

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

1999-01-01

307

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

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

RachaelBrown

2014-03-01

308

Inhibition of NO synthesis does not potentiate dynamic cardiovascular response to sympathetic nerve activity.  

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We examined whether the inhibition of nitric oxide (NO) synthesis potentiates the dynamic sympathetic regulation of the cardiovascular system through the baroreflex. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses to evoke random changes in sympathetic nerve activity (SNA). We estimated the transfer functions from SNA to both aortic pressure (AoP) and heart rate (HR). The inhibition of NO synthesis by NG-monomethyl-L-arginine (L-NMMA, 40 mg/ kg) altered neither the transfer function from SNA to AoP nor that from SNA to HR. In contrast, sodium nitroprusside (3-6 micrograms.kg-1.min-1) significantly decreased the steady-state gain (40.3 +/- 11.7% of the control, P < 0.05) of the transfer function from SNA to AoP without affecting the HR responses. We conclude that the basal release of NO may have a role in the tonic blood pressure regulation, whereas it may not be involved in the dynamic sympathetic regulation of AoP or HR through the baroreflex. PMID:9249472

Miyano, H; Kawada, T; Sugimachi, M; Shishido, T; Sato, T; Alexander, J; Sunagawa, K

1997-07-01

309

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

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

Alessandra Deise Sebben

2011-01-01

310

Protease activity in brain, nerve, and muscle of hens given neuropathy-inducing organophosphates and a calcium channel blocker.  

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Activity of calcium-activated neutral protease (CANP or calpain), an enzyme responsible for degradation of axonal and muscle cytoskeletal elements, was determined in brain, sciatic nerve, and gastrocnemius muscle of hens given tri-ortho-tolyl phosphate (TOTP, 360 mg/kg po) or active congener phenyl saligenin phosphate (PSP, 2.5 mg/kg im) with and without a calcium channel blocker which ameliorated clinical signs of organophosphate-induced delayed neuropathy (nifedipine 1 mg/kg/day x 5). Calcium channel blocker administration was initiated 1 day prior to administration of organophosphate (OP). OP administration caused an increase in CANP activity in brain within 4 days and in sciatic nerve and gastrocnemius muscle within 2 days of administration. This increase did not occur if nifedipine was administered to PSP-treated hens. Total sciatic nerve calcium concentrations were also increased by PSP, but not until OP-treated hens were no longer being administered calcium blockers. This indicates that calcium channel blockers may contribute to amelioration of organophosphate-induced delayed neuropathy by attenuation of calcium-mediated disruption of axonal and muscle cytoskeletal homeostasis. PMID:2156356

el-Fawal, H A; Correll, L; Gay, L; Ehrich, M

1990-03-15

311

Sulindac derivatives inhibit cell growth and induce apoptosis in primary cells from malignant peripheral nerve sheath tumors of NF1-patients  

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Full Text Available Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs are neoplasms leading to death in most cases. Patients with Neurofibromatosis type 1 have an increased risk of developing this malignancy. The metabolites of the inactive prodrug Sulindac, Sulindac Sulfide and Sulindac Sulfone (Exisulind are new chemopreventive agents that show promising results in the treatment of different cancer types. In this study we examined the antineoplastic effect of these compounds on primary cells derived from two MPNSTs of Neurofibromatosis type 1 patients. Results Exisulind and Sulindac Sulfide showed a dramatic time- and dose-dependent growth inhibitory effect with IC50-values of 120 ?M and 63 ?M, respectively. The decrease in viability of the tested cells correlated with induction of apoptosis. Treatment with 500 ?M Exisulind and 125 ?M Sulindac Sulfide for a period of 2 days increased the rate of apoptosis 21-27-fold compared to untreated cells. Reduced expression of RAS-GTP and phosphorylated ERK1/2 was detected in treated MPNST cells. Moreover, elevated levels of phosphorylated SAPK/JNK were found after drug treatment, and low activation of cleaved caspase-3 was seen. Conclusions Our results suggest that this class of compounds may be of therapeutic benefit for Neurofibromatosis type 1 patients with MPNST.

Friedrich Reinhard E

2004-05-01

312

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

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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, may modulate the activity of the sympathetic nervous system. The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS. In a randomized controlled trial, 20 women with PCOS were randomly allocated to one of three groups: low-frequency EA (n = 9), physical exercise (n = 5), or untreated control (n = 6) during 16 wk. Direct recordings of multiunit efferent postganglionic MSNA in a muscle fascicle of the peroneal nerve before and following 16 wk of treatment. Biometric, hemodynamic, endocrine, and metabolic parameters were measured. Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared with the untreated control group. The low-frequency EA group reduced sagittal diameter (P = 0.001), while the physical exercise group reduced body weight (P = 0.004) and body mass index (P = 0.004) compared with the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P correlation was found for body mass index and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine, and metabolic variables. 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. PMID:19494176

Stener-Victorin, Elisabet; Jedel, Elizabeth; Janson, Per Olof; Sverrisdottir, Yrsa Bergmann

2009-08-01

313

The acute effect of atrioventricular pacing on sympathetic nerve activity in patients with normal and depressed left ventricular function  

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Although modest elevations in pacing rate improve cardiac output and induce reflex sympathoinhibition, the threshold rate above which hemodynamic perturbations induce reflex sympathoexcitation remains unknown. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP) and sympathetic nerve activity (SNA) were measured during normal sinus rhythm (NSR) and atrioventricular (AV) sequential pacing in 25 patients. Pacing was performed at 100, 120, and 140 beat...

Segerson, Nathan M.; Wasmund, Stephen L.; Daccarett, Marcos; Fabela, Manuel L.; Hammond, Christopher H.; Stoddard, Gregory; Smith, Michael L.; Hamdan, Mohamed H.

2008-01-01

314

Desynchronization of electrically evoked auditory-nerve activity by high-frequency pulse trains of long durationa)  

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Rubinstein et al. [Hear. Res. 127, 108–118 (1999)] suggested that the neural representation of the waveforms of electric stimuli might be improved by introducing an ongoing, high-rate, desynchronizing pulse train (DPT). A DPT may desynchronize neural responses to electric stimulation in a manner similar to spontaneous activity in a healthy ear. To test this hypothesis, responses of auditory-nerve fibers (ANFs) to 10-min-long electric pulse trains (5 kpps) were recorded from acutely deafened...

Litvak, Leonid M.; Smith, Zachary M.; Delgutte, Bertrand; Eddington, Donald K.

2003-01-01

315

P2Y2 receptor activates nerve growth factor/TrkA signaling to enhance neuronal differentiation  

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Neurotrophins are essential for neuronal differentiation, but the onset and the intensity of neurotrophin signaling within the neuronal microenvironment are poorly understood. We tested the hypothesis that extracellular nucleotides and their cognate receptors regulate neurotrophin-mediated differentiation. We found that 5?-O-(3-thio)triphosphate (ATP?S) activation of the G protein-coupled receptor P2Y2 in the presence of nerve growth factor leads to the colocalization and association of ty...

Arthur, David B.; Akassoglou, Katerina; Insel, Paul A.

2005-01-01

316

Human Schwann Cells Seeded on a Novel Collagen-Based Microstructured Nerve Guide Survive, Proliferate, and Modify Neurite Outgrowth  

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A variety of new bioartificial nerve guides have been tested preclinically for their safety and nerve regeneration supporting properties. So far, only a limited number of biomaterials have been tested in humans since the step from preclinical work to a clinical application is challenging. We here present an in vitro model with human Schwann cells (hSCs) as an intermediate step towards clinical application of the nerve guide Perimaix, a collagen-based microstructured 3D scaffold containing numerous longitudinal guidance channels for directed axonal growth. hSCs were seeded onto different prototypes of Perimaix and cultivated for 14 days. hSC adhered to the scaffold, proliferated, and demonstrated healthy Schwann cell morphology (spindle shaped cell bodies, bipolar oriented processes) not only at the surface of the material, but also in the deeper layers of the scaffold. The general well-being of the cells was quantitatively confirmed by low levels of lactate dehydrogenase release into the culture medium. Moreover, conditioned medium of hSCs that were cultivated on Perimaix was able to modify neurite outgrowth from sensory dorsal root ganglion neurons. Overall these data indicate that Perimaix is able to provide a matrix that can promote the attachment and supports process extension, migration, and proliferation of hSC.

van Neerven, Sabien G. A.; Haastert-Talini, Kirsten; Tolba, Rene H.; Pallua, Norbert; Bozkurt, Ahmet

2014-01-01

317

p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination.  

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Physical damage to the peripheral nerves triggers Schwann cell injury response in the distal nerves in an event termed Wallerian degeneration: the Schwann cells degrade their myelin sheaths and dedifferentiate, reverting to a phenotype that supports axon regeneration and nerve repair. The molecular mechanisms regulating Schwann cell plasticity in the PNS remain to be elucidated. Using both in vivo and in vitro models for peripheral nerve injury, here we show that inhibition of p38 mitogen-activated protein kinase (MAPK) activity in mice blocks Schwann cell demyelination and dedifferentiation following nerve injury, suggesting that the kinase mediates the injury signal that triggers distal Schwann cell injury response. In myelinating cocultures, p38 MAPK also mediates myelin breakdown induced by Schwann cell growth factors, such as neuregulin and FGF-2. Furthermore, ectopic activation of p38 MAPK is sufficient to induce myelin breakdown and drives differentiated Schwann cells to acquire phenotypic features of immature Schwann cells. We also show that p38 MAPK concomitantly functions as a negative regulator of Schwann cell differentiation: enforced p38 MAPK activation blocks cAMP-induced expression of Krox 20 and myelin proteins, but induces expression of c-Jun. As expected of its role as a negative signal for myelination, inhibition of p38 MAPK in cocultures promotes myelin formation by increasing the number as well as the length of individual myelin segments. Altogether, our data identify p38 MAPK as an important regulator of Schwann cell plasticity and differentiation. PMID:22623660

Yang, David P; Kim, Jihyun; Syed, Neeraja; Tung, Young-John; Bhaskaran, Ambily; Mindos, Thomas; Mirsky, Rhona; Jessen, Kristjan R; Maurel, Patrice; Parkinson, David B; Kim, Haesun A

2012-05-23

318

Nestin-expressing stem cells from the hair follicle can differentiate into motor neurons and reduce muscle atrophy after transplantation to injured nerves.  

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We have previously shown that nestin-expressing hair follicle stem cells from the mouse and human are multipotent and can differentiate into many cell types, including neurons and glial cells. The nestin-expressing hair follicle stem cells can effect nerve and spinal cord repair upon transplantation in mouse models. In the present study, nestin-expressing hair follicle stem cells expressing red fluorescent protein (RFP) were induced by retinoic acid and fetal bovine serum to differentiate and then transplanted together with Matrigel into the transected distal sciatic or tibial nerve stump of transgenic nude mice ubiquitously expressing green fluorescent protein (GFP). Control mice were transplanted with Matrigel only. The transplanted cells appeared neuron like, with large round nuclei and long extensions. Immunofluorescence staining showed that some of the transplanted cells in the distal nerve stump expressed the neuron marker Tuj1 as well as motor neuron markers Isl 1/2 and EN1. These transplanted cells contacted each other as well as host nerve fibers. Two weeks post-transplantation, nerve fibers in the distal sciatic nerve stump of the transplanted mice had greater expression of motor neuron markers and neurotrophic factor-3 than those in the Matrigel-only transplanted mice. Muscle fiber areas in the nestin-expressing stem cell plus Matrigel-transplanted animals were much bigger than that in the Matrigel-only transplanted animals after 4 weeks. The present results suggest that transplanted nestin-expressing hair follicle stem cells can differentiate into motor neurons and reduce muscle atrophy after sciatic nerve transection. This study demonstrates a new and accessible neuron source to reduce muscle atrophy after nerve injury. PMID:24020586

Liu, Fang; Zhang, Chuansen; Hoffman, Robert M

2014-02-01

319

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

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

MasashiIchinose

2012-08-01

320

Calcium dependence of the priming, activation and inactivation of ryanodine receptors in frog motor nerve terminals.  

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We studied the effects of varying extracellular Ca(2+) ([Ca(2+) ](o) ) and Ca(2+) channel density and intracellular loading of Ca(2+) chelators on stimulation-induced rises in intracellular Ca(2+) ([Ca(2+) ](i) ) in frog motor nerve terminals with Ca(2+) imaging. The slowly waxing and waning components of rises in [Ca(2+) ](i) induced by repetitive tetani were suppressed by blockers of Ca(2+) pumps of the endoplasmic reticulum (thapsigargin and cyclopiazonic acid) and a blocker of ryanodine receptors [8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride] without affecting the initial quickly-rising component, thus reflecting the priming (and then subsequent rapid activation) and inactivation phases of Ca(2+) -induced Ca(2+) release (CICR) from the endoplasmic reticulum. A short tetanus-induced rise in [Ca(2+) ](i) was proportional to [Ca(2+) ](o) , whereas the component of CICR was non-linearly related to [Ca(2+) ](o) with saturation at 0.9?mm. The progressive blockade of Ca(2+) channels by ?-conotoxin GVIA caused proportional decreases in CICR and short tetanus-induced [Ca(2+) ](i) rises. Intracellular loading of BAPTA and EGTA reduced the magnitude of CICR as well as short tetanus-induced rises in [Ca(2+) ](i) with a greater effect of BAPTA than EGTA on CICR. The time to peak and the half decay time of CICR were prolonged by a low [Ca(2+) ](o) or Ca(2+) channel blocker or [Ca(2+) ](i) chelators. These results suggest that ryanodine receptors sense the high [Ca(2+) ](i) transient following single action potentials for triggering CICR, whereas the priming and inactivation processes of CICR sense a slower, persisting rise in [Ca(2+) ](i) during and after action potential trains. A model is presented that includes CICR activation in elementary units. PMID:20796022

Soga-Sakakibara, Satoko; Kubota, Masakazu; Suzuki, Sinichi; Akita, Tenpei; Narita, Kazuhiko; Kuba, Kenji

2010-09-01

 
 
 
 
321

Cdc42 GTPases facilitate TNF-?-mediated secretion of CCL2 from peripheral nerve microvascular endoneurial endothelial cells.  

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Trafficking of autoreactive leukocytes across the blood-nerve barrier and into peripheral nerves is an early pathological hallmark of Guillain-Barré syndrome (GBS). Tumor necrosis factor-? (TNF-?), a proinflammatory cytokine, promotes transendothelial migration by upregulating endothelial expression of inflammatory mediators, including CCL2, a chemokine implicated in GBS. We sought to determine the mechanism by which TNF-? induces expression and secretion of CCL2 from peripheral nerve microvascular endoneurial endothelial cells (PNMECs). Expression of CCL2 mRNA and protein in quiescent PNMEC cultures was minimal. In contrast, cultures treated with TNF-? exhibited increased CCL2 mRNA and protein content, as well as protein secretion. Simvastatin significantly attenuated TNF-?-induced CCL2 secretion without affecting CCL2 mRNA or protein expression. Co-incubation with geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, prevented the effect of simvastatin. By comparison, inhibiting protein isoprenylation with GGTI-298, but not FTI-277, mimicked the effect of simvastatin and significantly attenuated transendothelial migration in vitro. Inhibition of the monomeric GTPase Cdc42, but not Rac1 or RhoA-C, attenuated TNF-?-mediated CCL2 secretion. TNF-?-mediated trafficking of autoreactive leukocytes into peripheral nerves during GBS may proceed by a mechanism that involves Cdc42-facilitated secretion of CCL2. PMID:24028188

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

2013-09-01

322

Hydrogen-Rich Saline Promotes Survival of Retinal Ganglion Cells in a Rat Model of Optic Nerve Crush  

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Objective To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC). Methods We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) could be protected by H2. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated. Results H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H2 group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR. Conclusion These results demonstrated that H2 protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.

Zuo, Qiao; Wang, Ruo-bing; Qi, Ai-qing; Cao, Wen-luo; Sun, Ai-jun; Sun, Xue-jun; Xu, Jiajun

2014-01-01

323

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

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

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

2011-07-01

324

Effects of Yiqi Huayu Recipe on neural cell adhesion molecule in rats with lumbar nerve root compression  

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Full Text Available Objective: To study the effects of Yiqi Huayu Recipe on neural cell adhesion molecule (N-CAM in neuromuscular junctions during nerve regeneration in rats with lumbar nerve root compression. Methods: The rats with lumbar nerve root compression were given Yiqi Huayu Recipe for 10, 20 and 30 days respectively. The distribution of N-CAM in neuromuscular junctions of soleus muscle in rats was examined with immunohistochemical method and confocal laser scanning microscopy technique. The acetylcholine receptor (AChR was visualized with fluorescein-conjugated ?-bungarotoxin (?-BTX. The overlap areas of N-CAM and AChR sites were measured with NIH image technique.Results: The aggregates, sprouts and extensions of N-CAM in the neuromuscular junctions and the overlap areas of N-CAM and AChR sites in the Yiqi Huayu Recipe-treated group were all better improved than those in the untreated group. Conclusion: The expression of N-CAM is regulated according to the state of innervation for muscles. Yiqi Huayu Recipe may accelerate this nerve regeneration process.

Chong-Jian ZHOU

2006-03-01

325

Inner ester derivatives of gangliosides protect autonomic nerves of alloxan-diabetic rats against Na+, K(+)-ATPase activity defects.  

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Bovine brain gangliosides have been shown to prevent decay in Na+,K(+)-ATPase activity in sciatic and optic nerves of alloxan- and streptozotocin-diabetic rats. In the search for a drug with greater bioavailability and increased incorporation into neural tissue, ganglioside inner ester derivatives (AGF1) were recently developed. We evaluated the effect of AGF1 treatment on Na+,K(+)-ATPase activity in homogenates of vagus nerve from alloxan-diabetic rats (100 mg/kg s.c.). Animals were treated with AGF1: 10 mg/kg 6 days/week i.p., or 30 mg/kg biweekly i.p. Treatment began 10 d post-alloxan and continued for 8 consecutive weeks. Normal age- and sex-matched rats were used as controls. Alloxan intoxication produced a 39% decrease in Na+,K(+)-ATPase activity of the vagus nerve, which was completely restored (96-97% recovery) by both AGF1 regimes. Results suggest that ganglioside inner ester derivatives may be used in the clinical setting for the management of diabetic autonomic neuropathy. PMID:1652421

Bianchi, R; Triban, C; Marini, P; Figliomeni, B; Paro, M; Italiano, G; Prosdocimi, M; Fiori, M G

1991-05-01

326

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

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

RachaelBrown

2012-10-01

327

Challenges and opportunities in processing muscle sympathetic nerve activity with wavelet denoising techniques: detecting single action potentials in multiunit sympathetic nerve recordings in humans.  

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An important issue in analysis of muscle sympathetic nerve activity (MSNA), particularly those measures made in humans, is the problem that background noise of varying levels from recording to recording may interfere with accurate assessment of neural discharge patterns and overall activity. In this study, the utility of wavelet denoising approaches for processing MSNA signals was examined with emphasis on 1) determining whether this approach could improve the signal-to-noise (SNR) in the integrated neurogram, and 2) detecting intra-burst single action potential spikes. The utility of wavelet denoising was examined in simulated data and in original human data with three recordings of varying SNR (low, moderate and high) obtained from two healthy individuals. Only in the high SNR signal was the noise removed without concurrent loss of signal. Using a threshold-detecting algorithm individual depolarization spikes were detected in denoised recordings of high original SNR (>3:1) from four individuals and the interspike interval characteristics of these were quantified on a burst-by-burst basis. Compared with baseline (15+/-1 spikes/burst) a reflexive increase in spike count (29+/-4 spikes/burst) was observed during a held maximal inspiration (Pdenoising to enhance detection of neural bursts in the integrated neurogram of MSNA. However, opportunities exist with this approach to detect variations in action potential contributions within each burst of MSNA. This latter observation suggests that this denoising approach provides a new probe to explore MSNA discharge patterns. PMID:17412648

Zhang, Qing; Liu, Yinchun; Brown, L; Shoemaker, J Kevin

2007-07-31

328

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

Science.gov (United States)

Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat. PMID:20149260

Amado, Sandra; Rodrigues, Jorge M; Luís, Ana L; Armada-da-Silva, Paulo A S; Vieira, Márcia; Gartner, Andrea; Simões, Maria J; Veloso, António P; Fornaro, Michele; Raimondo, Stefania; Varejão, Artur S P; Geuna, Stefano; Maurício, Ana C

2010-01-01

329

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

International Nuclear Information System (INIS)

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

2005-07-01

330

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

Directory of Open Access Journals (Sweden)

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

Herold, Christian

2013-10-01

331

Neurotensin receptor involvement in the rise of extracellular glutamate levels and apoptotic nerve cell death in primary cortical cultures after oxygen and glucose deprivation.  

Science.gov (United States)

In view of the ability of neurotensin (NT) to increase glutamate release, the role of NT receptor mechanisms in oxygen-glucose deprivation (OGD)-induced neuronal degeneration in cortical cultures has been evaluated by measuring lactate dehydrogenase (LDH) levels, mitochondrial dehydrogenase activity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide levels, and microtubule-associated protein 2 (MAP2) immunoreactivity. Apoptotic nerve cell death was analyzed measuring chromatin condensation with Hoechst 33258, annexin V staining, and caspase-3 activity. Furthermore, the involvement of glutamate excitotoxicity in the neurodegeneration-enhancing actions of NT was analyzed by measurement of extracellular glutamate levels. NT enhanced the OGD-induced increase of LDH, endogenous extracellular glutamate levels, and apoptotic nerve cell death. In addition, the peptide enhanced the OGD-induced loss of mitochondrial functionality and increase of MAP2 aggregations. These effects were blocked by the neurotensin receptor 1 (NTR1) antagonist SR48692. Unexpectedly, the antagonist at 100 nM counteracted not only the NT effects but also some OGD-induced biochemical and morphological alterations. These results suggest that NTR1 receptors may participate in neurodegenerative events induced by OGD in cortical cultures, used as an in vitro model of cortical ischemia. The NTR1 receptor antagonists could provide a new tool to explore the clinical possibilities and thus to move from chemical compound to effective drug. PMID:18063561

Antonelli, Tiziana; Tomasini, Maria C; Fournier, Jacqueline; Mazza, Roberta; Tanganelli, Sergio; Pirondi, Stefania; Fuxe, Kjell; Ferraro, Luca; Luca, Ferraro

2008-08-01

332

Hepatocytes Express Nerve Growth Factor during Liver Injury : Evidence for Paracrine Regulation of Hepatic Stellate Cell Apoptosis  

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A key feature of recovery from liver fibrosis is hepatic stellate cell (HSC) apoptosis, which serves the dual function of removing the major source of neomatrix and tissue inhibitors of metalloproteinases thereby facilitating matrix degradation. The mechanisms regulating HSC apoptosis remain undefined but may include the interaction of nerve growth factor (NGF) with its receptor, p75, on HSC. In this study, by TaqMan polymerase chain reaction in situ hybridization and immunohistochemistry, we...

Oakley, Fiona; Trim, Nathan; Constandinou, Christothea M.; Ye, Weilan; Gray, Alane M.; Frantz, Gretchen; Hillan, Kenneth; Kendall, Tim; Benyon, R. Christopher; Mann, Derek A.; Iredale, John P.

2003-01-01

333

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

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Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve growth factor (NGF) could induce expression of the delta opioid receptor gene (Oprd1, dor), mainly through PI3K/Akt/NF-?B signaling in PC12h cells. In this study, using two NGF-responsiv...

Dwaipayan Sen; Michael Huchital; Chen, Yulong L.

2013-01-01

334

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

Science.gov (United States)

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

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

2010-07-01

335

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

Directory of Open Access Journals (Sweden)

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

Pan Hung-Chuan

2009-08-01

336

Nerve biopsy  

Science.gov (United States)

Abnormal results may be due to: Amyloidosis (sural nerve biopsy is most often used) Demyelination Inflammation of the nerve Leprosy Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis

337

Desynchronization of electrically evoked auditory-nerve activity by high-frequency pulse trains of long duration  

Science.gov (United States)

Rubinstein et al. [Hear. Res. 127, 108-118 (1999)] suggested that the neural representation of the waveforms of electric stimuli might be improved by introducing an ongoing, high-rate, desynchronizing pulse train (DPT). A DPT may desynchronize neural responses to electric stimulation in a manner similar to spontaneous activity in a healthy ear. To test this hypothesis, responses of auditory-nerve fibers (ANFs) to 10-min-long electric pulse trains (5 kpps) were recorded from acutely deafened, anesthetized cats. Stimuli were delivered via an intracochlear electrode, and their amplitude was chosen to elicit a response in most ANFs. Responses to pulse trains showed pronounced adaptation during the first 1-2 min, followed by either a sustained response or cessation of spike discharges for the remainder of the stimulus. The adapted discharge rates showed a broad distribution across the ANF population like spontaneous activity. However, a higher proportion of fibers (46%) responded to the DPT at rates below 5 spikes/s than for spontaneous activity, and 12% of the fibers responded at higher rates than any spontaneously active fiber. Interspike interval histograms of sustained responses for some fibers had Poisson-like (exponential) shapes, resembling spontaneous activity, while others exhibited preferred intervals and, occasionally, bursting. Simultaneous recordings from pairs of fibers revealed no evidence of correlated activity, suggesting that the DPT does desynchronize the auditory nerve activity. Overall, these results suggest that responses to an ongoing DPT resemble spontaneous activity in a normal ear for a substantial fraction of the ANFs.

Litvak, Leonid M.; Smith, Zachary M.; Delgutte, Bertrand; Eddington, Donald K.

2003-10-01

338

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

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

Oskar Grau Kaufmann

2009-12-01

339

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

Science.gov (United States)

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

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

2014-05-01

340

Effect of acute hypoxia on regional cerebral blood flow: effect of sympathetic nerve activity.  

Science.gov (United States)

We examined 1) whether global cerebral blood flow (CBF) would increase across a 6-h bout of normobaric poikilocapnic hypoxia and be mediated by a larger increase in blood flow in the vertebral artery (VA) than in the internal carotid artery (ICA); and 2) whether additional increases in global CBF would be evident following an ?1-adrenergic blockade via further dilation of the ICA and VA. In 11 young normotensive individuals, ultrasound measures of ICA and VA flow were obtained in normoxia (baseline) and following 60, 210, and 330 min of hypoxia (FiO2 = 0.11). Ninety minutes prior to final assessment, participants received an ?1-adrenoreceptor blocker (prazosin, 1 mg/20 kg body mass) or placebo. Compared with baseline, following 60, 220, and 330 min of hypoxia, global CBF [(ICAFlow + VAFlow) ? 2] increased by 160 ± 52 ml/min (+28%; P = 0.05), 134 ± 23 ml/min (+23%; P = 0.02), and 113 ± 51 (+19%; P = 0.27), respectively. Compared with baseline, ICAFlow increased by 23% following 60 min of hypoxia (P = 0.06), after which it progressively declined. The percentage increase in VA flow was consistently larger than ICA flow during hypoxia by ?20% (P = 0.002). Compared with baseline, ICA and VA diameters increased during hypoxia by ?9% and ?12%, respectively (P ? 0.05), and were correlated with reductions in SaO2. Flow and diameters were unaltered following ?1 blockade (P ? 0.10). In conclusion, elevations in global CBF during acute hypoxia are partly mediated via greater increases in VA flow compared with ICA flow; this regional difference was unaltered following ?1 blockade, indicating that a heightened sympathetic nerve activity with hypoxia does not constrain further dilation of larger extracranial blood vessels. PMID:24610534

Lewis, Nia C S; Messinger, Laura; Monteleone, Brad; Ainslie, Philip N

2014-05-01

 
 
 
 
341

p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination  

Science.gov (United States)

Physical damage to the peripheral nerves triggers Schwann cell injury response in the distal nerves in an event termed Wallerian degeneration: the Schwann cells degrade their myelin sheaths and de-differentiate, reverting to a phenotype that supports axon regeneration and nerve repair. The molecular mechanisms regulating Schwann cell plasticity in the PNS remain to be elucidated. Using both in vivo and in vitro models for peripheral nerve injury, here we show that inhibition of p38 MAPK activity in mice blocks Schwann cell demyelination and de-differentiation following nerve injury, suggesting that the kinase mediates the injury signal that triggers distal Schwann cell injury response. In myelinating co-cultures, p38 MAPK also mediates myelin breakdown induced by Schwann cell growth factors, such as neuregulin and FGF-2. Furthermore, ectopic activation of p38 MAPK is sufficient to induce myelin breakdown and drives differentiated Schwann cells to acquire phenotypic features of immature Schwann cells. We also show that p38 MAPK concomitantly functions as a negative regulator of Schwann cell differentiation: enforced p38 MAPK activation blocks cAMP-induced expression of Krox 20 and myelin proteins, but induces expression of c-Jun. As expected of its role as a negative signal for myelination, inhibition of p38 MAPK in co-cultures promotes myelin formation by increasing the number as well as the length of individual myelin segments. Altogether, our data identify p38 MAPK as an important regulator of Schwann cell plasticity and differentiation.

Yang, David P.; Kim, Jihyun; Syed, Neeraja; Tung, Young-john; Bhaskaran, Ambily; Mindos, Thomas; Mirsky, Rhona; Jessen, Kristjan R.; Maurel, Patrice; Parkinson, David B.; Kim, Haesun A.

2012-01-01

342

Biological Activity of Nerve Growth Factor Precursor Is Dependent upon Relative Levels of Its Receptors*  

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Nerve growth factor (NGF) is produced as a precursor called pro-nerve growth factor (proNGF), which is secreted by many tissues and is the predominant form of NGF in the central nervous system. In Alzheimer disease brain, cholinergic neurons degenerate and can no longer transport NGF as efficiently, leading to an increase in untransported NGF in the target tissue. The protein that accumulates in the target tissue is proNGF, not the mature form. The role of this precursor is controversial, and...

Masoudi, Raheleh; Ioannou, Maria S.; Coughlin, Michael D.; Pagadala, Promila; Neet, Kenneth E.; Clewes, Oliver; Allen, Shelley J.; Dawbarn, David; Fahnestock, Margaret

2009-01-01

343

Chronic variable stress activates hematopoietic stem cells.  

Science.gov (United States)

Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex. It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the ?3-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe(-/-) mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans. PMID:24952646

Heidt, Timo; Sager, Hendrik B; Courties, Gabriel; Dutta, Partha; Iwamoto, Yoshiko; Zaltsman, Alex; von Zur Muhlen, Constantin; Bode, Christoph; Fricchione, Gregory L; Denninger, John; Lin, Charles P; Vinegoni, Claudio; Libby, Peter; Swirski, Filip K; Weissleder, Ralph; Nahrendorf, Matthias

2014-07-01

344

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

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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 cel...

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

2002-01-01

345

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

Science.gov (United States)

The nervous and endocrine systems jointly control intestinal movements, secretions of their glands and also participate of the processes of nutrient digestion and absorption. Therefore, the central objective of this study was to verify the existence of a possible relationship between the number of nervous cells and ganglia of the submucosal and myenteric plexuses and the number of endocrine cells in the small intestine of adult D. aurita. The utilized staining techniques were Grimelius, modified Masson-Fontana, direct immunoperoxidase and H-E. Argyrophillic, argentaffin and insulin immunoreactive endocrine cells do not numerically vary between the initial, mid and final regions of the duodenum, jejunum and ileum (P>0.05), except for argyrophillic cells in the jejunum (P>0.05). No numerical relationship has yet been verified between the number of nerve ganglia and endocrine cells, and also between nervous and endocrine cells. We recommended the use of new immunohistochemical techniques to confirm the numerical correlation between the nervous and endocrine systems in the small intestine. The morphology and distribution of endocrine cells and the nerve ganglia studied were similar to those encountered in eutherian mammals. PMID:22801379

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

2012-09-01

346

Enhancement of peripheral nerve regeneration by pharmacological activation of the cyclic AMP second messenger system.  

Science.gov (United States)

This paper reviews the history of attempts to study peripheral nerve regeneration, focusing upon pharmacologic agents that may prove to be useful clinically. In particular, forskolin is described as a model for such an agent, and its mechanism of action, as a stimulator of the cyclic AMP second messenger system, is described. PMID:2549330

Klein, H W; Kilmer, S; Carlsen, R C

1989-01-01

347

Perineural spread of cutaneous basal and squamous cell carcinomas. The clinical appearance of spread into the trigeminal and facial nerves.  

Science.gov (United States)

Five patients were studied in whom a trigeminal or facial neuropathy resulted from perineural spread of basal or squamous cell carcinomas arising in the skin of the face. The cause of the neuropathy was not immediately apparent because there was no evidence of local skin recurrence in any of the patients after the onset of their neurologic symptoms. Pain was a prominent feature in those patients with trigeminal involvement. Radiologic investigations were helpful in only one patient. The diagnosis should be suspected when symptoms and signs are confined initially to superficial branches of the trigeminal or facial nerves and later extend to more central branches in the order in which they arise. Confirmation can be made by microscopic examination of the nerves involved. PMID:6860179

Morris, J G; Joffe, R

1983-07-01

348

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

LENUS (Irish Health Repository)

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

Irnaten, Mustapha

2009-01-01

349

Macular Retinal Ganglion Cell Complex Thickness and Its Relationship to the Optic Nerve Head Topography in Glaucomatous Eyes with Hemifield Defects  

Science.gov (United States)

Purpose. To evaluate the relationship between the macular ganglion cell complex (mGCC) thickness, which is the sum of the retinal nerve fiber, ganglion cell, and inner plexiform layers, measured with a spectral-domain optical coherence tomograph and the optic nerve head topography measured with a confocal scanning laser ophthalmoscope in glaucomatous eyes with visual field defects localized predominantly to either hemifield. Materials and Methods. The correlation between the mGCC thickness in hemispheres corresponding to hemifields with and without defects (damaged and intact hemispheres, respectively) and the optic nerve head topography corresponding to the respective hemispheres was evaluated in 18 glaucomatous eyes. Results. The mGCC thickness was significantly correlated with the rim volume, mean retinal nerve fiber layer thickness, and cross-sectional area of the retinal nerve fiber layer in both the intact and the damaged hemispheres (P < .05). Discussion. For detecting very early glaucomatous damage of the optic nerve, changes in the thicknesses of the inner retina in the macular area and peripapillary RNFL as well as rim volume changes in the optic nerve head are target parameters that should be carefully monitored.

Takagi, Seiji T.; Kita, Yoshiyuki; Takeyama, Asuka; Tomita, Goji

2011-01-01

350

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 rats and the proportions of surviving and neurite-extending cells were determined after 8 days in culture. In the presence of C6-CM virtually all seeded cells survived and 50% developed neuritic proce...

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

1984-01-01

351

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

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

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

1996-01-01

352

Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.  

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Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites...

1991-01-01

353

Mindfulness meditation lowers muscle sympathetic nerve activity and blood pressure in African-American males with chronic kidney disease.  

Science.gov (United States)

Mindfulness meditation (MM) is a stress-reduction technique that may have real biological effects on hemodynamics but has never previously been tested in chronic kidney disease (CKD) patients. In addition, the mechanisms underlying the potential blood pressure (BP)-lowering effects of MM are unknown. We sought to determine whether MM acutely lowers BP in CKD patients, and whether these hemodynamic changes are mediated by a reduction in sympathetic nerve activity. In 15 hypertensive African-American (AA) males with CKD, we conducted a randomized, crossover study in which participants underwent 14 min of MM or 14 min of BP education (control intervention) during two separate random-order study visits. Muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, heart rate (HR), and respiratory rate (RR) were continuously measured at baseline and during each intervention. A subset had a third study visit to undergo controlled breathing (CB) to determine whether a reduction in RR alone was sufficient in exacting hemodynamic changes. We observed a significantly greater reduction in systolic BP, diastolic BP, mean arterial pressure, and HR, as well as a significantly greater reduction in MSNA, during MM compared with the control intervention. Participants had a significantly lower RR during MM; however, in contrast to MM, CB alone did not reduce BP, HR, or MSNA. MM acutely lowers BP and HR in AA males with hypertensive CKD, and these hemodynamic effects may be mediated by a reduction in sympathetic nerve activity. RR is significantly lower during MM, but CB alone without concomitant meditation does not acutely alter hemodynamics or sympathetic activity in CKD. PMID:24829497

Park, Jeanie; Lyles, Robert H; Bauer-Wu, Susan

2014-07-01

354

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

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

A.L.R. Oliveira

2001-03-01

355

A mouse model of Schwartz-Jampel syndrome reveals myelinating Schwann cell dysfunction with persistent axonal depolarization in vitro and distal peripheral nerve hyperexcitability when perlecan is lacking.  

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Congenital peripheral nerve hyperexcitability (PNH) is usually associated with impaired function of voltage-gated K(+) channels (VGKCs) in neuromyotonia and demyelination in peripheral neuropathies. Schwartz-Jampel syndrome (SJS) is a form of PNH that is due to hypomorphic mutations of perlecan, the major proteoglycan of basement membranes. Schwann cell basement membrane and its cell receptors are critical for the myelination and organization of the nodes of Ranvier. We therefore studied a mouse model of SJS to determine whether a role for perlecan in these functions could account for PNH when perlecan is lacking. We revealed a role for perlecan in the longitudinal elongation and organization of myelinating Schwann cells because perlecan-deficient mice had shorter internodes, more numerous Schmidt-Lanterman incisures, and increased amounts of internodal fast VGKCs. Perlecan-deficient mice did not display demyelination events along the nerve trunk but developed dysmyelination of the preterminal segment associated with denervation processes at the neuromuscular junction. Investigating the excitability properties of the peripheral nerve suggested a persistent axonal depolarization during nerve firing in vitro, most likely due to defective K(+) homeostasis, and excluded the nerve trunk as the original site for PNH. Altogether, our data shed light on perlecan function by revealing critical roles in Schwann cell physiology and suggest that PNH in SJS originates distally from synergistic actions of peripheral nerve and neuromuscular junction changes. PMID:22449950

Bangratz, Marie; Sarrazin, Nadège; Devaux, Jérôme; Zambroni, Désirée; Echaniz-Laguna, Andoni; René, Frédérique; Boërio, Delphine; Davoine, Claire-Sophie; Fontaine, Bertrand; Feltri, Maria Laura; Benoit, Evelyne; Nicole, Sophie

2012-05-01

356

Best1 is a gene regulated by nerve injury and required for Ca2+-activated Cl? current expression in axotomized sensory neurons  

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We investigated the molecular determinants of Ca2+-activated chloride current (CaCC) expressed in adult sensory neurons following a nerve injury. Dorsal root ganglia express the transcripts of three gene families known to induce CaCCs in heterologous systems: bestrophin, tweety and TMEM16. We found with quantitative transcriptional analysis and in situ hybridization that nerve injury induced upregulation of solely bestrophin-1 transcripts in sensory neurons. Gene screening with RNA interferen...

Boudes, Mathieu; Sar, Chamroeun; Menigoz, Aure?lie; Hilaire, Ce?cile; Pe?quignot, Marie; Kozlenkov, Alexei; Marmorstein, Alan; Carroll, Patrick; Valmier, Jean; Scamps, Fre?de?rique

2009-01-01

357

Prosaposin facilitates sciatic nerve regeneration in vivo.  

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Prosaposin, a multifunctional protein, is the precursor of saposins, which activate sphingolipid hydrolases. In addition to acting as a precursor for saposins, prosaposin has been shown to rescue hippocampal CA1 neurons from lethal ischemic damage in vivo and to promote neurite extension of neuroblastoma cells in vitro. Here we show that prosaposin, when added to a collagen-filled nerve guide after sciatic nerve transection in guinea pigs, increased dramatically the number of regenerating nerve fibers within the guide. To identify the target neurons of prosaposin during peripheral nerve regeneration, we determined the degree of atrophy and chromatolysis of neurons in the spinal anterior horn and dorsal root ganglia on the prosaposin-treated and untreated side. The effect of prosaposin on large spinal neurons and small neurons of the dorsal root ganglion was more conspicuous. Subsequent immunohistochemistry demonstrated that the atrophy of cholinergic large neurons in the anterior horn is prevented to significant extent by prosaposin treatment. These findings suggest that prosaposin promotes peripheral nerve regeneration by acting on alpha-motor neurons in the anterior horn and on small sensory neurons in the dorsal root ganglion. The present study raises the possibility of using prosaposin as a tool for the treatment of peripheral nerve injuries. PMID:8780031

Kotani, Y; Matsuda, S; Sakanaka, M; Kondoh, K; Ueno, S; Sano, A

1996-05-01

358

Neuroactive conducting scaffolds: nerve growth factor conjugation on active ester-functionalized polypyrrole  

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Electrically conductive and biologically active scaffolds are desirable for enhancing adhesion, proliferation and differentiation of a number of cell types such as neurons. Hence, the incorporation of neuroactive molecules into electroconductive polymers via a specific and stable method is essential for neuronal tissue engineering applications. Traditional conjugation approaches dramatically impair conductivities and/or stabilities of the scaffolds and ligands. In this study, we developed cop...

Lee, Jae Young; Lee, Joo-woon; Schmidt, Christine E.

2009-01-01

359

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

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Although coordinated actions of several areas within the hypothalamus are involved in the secretion of gonadotropin releasing hormone (GnRH), the median eminence of the hypothalamus, where the nerve terminals are located, plays a particularly critical role in the release of GnRH. In adult females, prior to the preovulatory surge of GnRH, the retraction of specialized ependymoglial cells lining the floor of the third ventricle named tanycytes allows for the juxtaposition of GnRH nerve terminal...

2010-01-01

360

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

Although coordinated actions of several areas within the hypothalamus are involved in the secretion of gonadotrophin-releasing hormone (GnRH), the median eminence of the hypothalamus, where the nerve terminals are located, plays a particularly critical role in the release of GnRH. In adult females, prior to the preovulatory surge of GnRH, the retraction of specialised ependymoglial cells lining the floor of the third ventricle named tanycytes allows for the juxtaposition of GnRH nerve termina...

2010-01-01