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Schwann cell metabolic activity in various short term holding conditions: implications for improved nerve graft viability  

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Strategies for improvement of nerve regeneration and optimal conditions to prevent Schwann cell (SC) loss within a nerve transplant procedure are critical. The purpose of this study was to examine SC viability, which plays an important role in peripheral nerve regeneration, under various incubation conditions up to three hours. To address this issue, Schwann cell metabolic activity was determined using different independent test methods. The following experimental conditions were compared: SC...

Insa Janssen; Kerstin Reimers; Christina Allmeling; Stella Matthes; Vogt, Peter M.; Christine Radtke

2012-01-01

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Stem Cell Transplantation for Auditory Nerve Replacement  

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The successful function of cochlear prostheses depends on activation of auditory nerve. The survival of auditory nerve neurons, however, can vary widely in candidates for cochlear implants and influence implant efficacy. Stem cells offer the potential for improving the function of cochlear prostheses and increasing the candidate pool by replacing lost auditory nerve. The first phase of studies for stem cell replacement of auditory nerve has examined the in vitro survival and differentiation a...

Altschuler, Richard A.; O’shea, K. Sue; Miller, Josef M.

2008-01-01

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Effect of experimental diabetes on Na/K-ATPase activity in red blood cells, peripheral nerve and kidney.  

Science.gov (United States)

A decrease in Na/K-ATPase activity is probably involved in the pathogenesis of diabetic neuropathy. In human diabetes, Na/K-ATPase activity is almost always studied in red blood cells, readily accessible, and it could represent a marker of predisposition to diabetic neuropathy. But, we wanted to establish whether diabetes induced similar changes of Na/K-ATPase activity in erythrocytes, and in other tissues, especially the peripheral nerve and the kidney. So, we compared Na/K-ATPase activity measured in the erythrocyte, sciatic nerve and kidney of rats with streptozotocin-induced diabetes after 8 weeks (n = 9) and normal rats (n = 9). Na/K-ATPase activity was 39-44% lower in the RBC, sciatic nerve and kidney of diabetic rats compared to controls (RBC: 229 +/- 79 vs. 413 +/- 102 p diabetes induces a parallel decrease in Na/K-ATPase activity in the red cell, sciatic nerve and kidney. The levels of this enzyme activity are significantly correlated in the red cell and sciatic nerve so that diabetes-induced changes of Na/K-ATPase activity in the erythrocyte seem to reflect those in the peripheral nerve. PMID:8001715

Raccah, D; Lamotte-Jannot, M F; Issautier, T; Vague, P

1994-01-01

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

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Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (Pmodel of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-?, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible. PMID:25010326

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

2014-09-01

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Stem cell transplantation for auditory nerve replacement.  

Science.gov (United States)

The successful function of cochlear prostheses depends on activation of auditory nerve. The survival of auditory nerve neurons, however, can vary widely in candidates for cochlear implants and influence implant efficacy. Stem cells offer the potential for improving the function of cochlear prostheses and increasing the candidate pool by replacing lost auditory nerve. The first phase of studies for stem cell replacement of auditory nerve has examined the in vitro survival and differentiation as well as in vivo differentiation and survival of exogenous embryonic and tissue stem cells placed into scala tympani and/or modiolus. These studies are reviewed and new results on in vivo placement of B-5 mouse embryonic stem cells into scala tympani of the guinea pig cochleae with differentiation into a glutamatergic neuronal phenotype are presented. Research on the integration and connections of stem cell derived neurons in the cochlea is described. Finally, an alternative approach is considered, based on the use of endogenous progenitors rather than exogenous stem cells, with a review of promising findings that have identified stem cell-like progenitors in cochlear and vestibular tissues to provide the potential for auditory nerve replacement. PMID:18585449

Altschuler, Richard A; O'Shea, K Sue; Miller, Josef M

2008-08-01

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Adipose derived stem cells and nerve regeneration.  

Science.gov (United States)

Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts. PMID:25221589

Faroni, Alessandro; Smith, Richard Jp; Reid, Adam J

2014-07-15

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Adipose derived stem cells and nerve regeneration  

Science.gov (United States)

Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.

Faroni, Alessandro; Smith, Richard JP; Reid, Adam J

2014-01-01

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Pharmacology of airway afferent nerve activity  

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

Carr Michael J

2001-05-01

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Resistance of nerve cells to oxidative injury  

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

Jovanovi? Zorica

2011-01-01

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Involvement of JunD in transcriptional activation of the orphan receptor gene nur77 by nerve growth factor and membrane depolarization in PC12 cells.  

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nur77, an immediate-early gene that encodes an orphan nuclear receptor, is rapidly and transiently induced by nerve growth factor (NGF) stimulation or membrane depolarization in the rat pheochromocytoma-derived cell line PC12. The Nur77 protein can act as a potent transcription activator and may function to regulate the expression of downstream genes in response to extracellular stimuli. We show here that activation of nur77 by NGF treatment and membrane depolarization is signalled through di...

Yoon, J. K.; Lau, L. F.

1994-01-01

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

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

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

2014-08-01

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Activation of MAPK ERK in peripheral nerve after injury  

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

Tanomsridejchai N

2006-06-01

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

International Nuclear Information System (INIS)

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

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[Fibrin matrix enhances adherence of peripheral nerve regenerative cells].  

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Optimal seeding of a nerve conduit with cells is a core problem in tissue engineering of constructing an artificial nerve substitute to gap lesions in the peripheral nerve system. An ideal nerve gap substitute would have to present an equally distributed number of cells that can activate the regrowing axons. This work shows a new in vitro technique of two-step seeding of cells inside a conduit and on layered mats that allows a valuable targeting of the cells and a proven survival in the environment of poly-3-hydroxybutyrate (PHB) conduits. The technique uses two components of diluted fibrin glue Tisseel. Initially, the chosen area on the mat was coated with thrombin followed from the seeding of a fibrinogen-cell compound. Using Sprague Dawley rat cells, we could demonstrate with immunohistochemistry (S100, DAPI) techniques that undifferentiated (uMSC) and Schwann cells (SC) mimicking differentiated mesenchymal stem cells (dMSC) as well as SC can be suspended and targeted significantly better in dissolvable diluted fibrin glue than in growth medium. Analysis showed significantly better values for adherence (p < 0.001) and drop off (p < 0.05) from seeded cells. Using this two-step application allows the seeding of the cells to be more precise and simplifies the handling of cell transplantation. PMID:18437664

Kalbermatten, D F; Kingham, P J; Mahay, D; Balcin, H; Pierer, G; Terenghi, G

2008-04-01

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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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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

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Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats.  

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With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5?×?10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair. PMID:22806359

Xu, Lin; Zhou, Shuai; Feng, Guo-Ying; Zhang, Lu-Ping; Zhao, Dong-Mei; Sun, Yi; Liu, Qian; Huang, Fei

2012-10-01

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How are the inner hair cells and auditory nerve fibers activated without the mediation of the outer hair cells and the cochlear amplifier?  

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The present study was designed to assess whether, in the presence of a depression of the cochlear amplifier i.e. a sensorineural hearing loss (SNHL), the inner hair cells (IHCs) require the presence of a normal endocochlear potential for transduction. An SNHL was induced by injecting salicylic acid (which binds to the motor protein prestin in the outer hair cells), and then furosemide (which depresses the endocochlear potential) was injected. Furosemide did not cause an additional elevation of the threshold of the auditory nerve brainstem evoked response (ABR) over that induced by the salicylic acid injection. Exposure to noise was also used to induce a SNHL in other mice, and then furosemide was injected. Here too furosemide did not cause an additional ABR threshold elevation over that induced by the noise. These results show that the IHCs (and the auditory nerve) can be excited in the presence of a SNHL (i.e. without the cochlear amplifier) and in the absence of an endocochlear potential. Possible mechanisms of excitation in such a state are discussed. PMID:21166271

Adelman, Cahtia; Weinberger, Jeffrey M; Sohmer, Haim

2010-01-01

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Nerve growth factor induces cord formation of mesenchymal stem cell by promoting proliferation and activating the PI3K/Akt signaling pathway  

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Aim: To investigate whether nerve growth factor (NGF) induced angiogenesis of bone marrow mesenchymal stem cells (MSCs) and the underlying mechanisms. Methods: Bone marrow MSCs were isolated from femors or tibias of Sprague-Dawley rat, and cultured. The cells were purified after 3 to 5 passages, seeded on Matrigel-coated 24-well plates and treated with NGF. Tube formation was observed 24 h later. Tropomyosin-related kinase A (TrkA) and p75NTR gene expression was examined using PCR analysis and flow cytometry. Growth curves were determined via cell counting. Expression of VEGF and pAkt/Akt were analyzed with Western blot. Results: NGF (25, 50, 100 and 200 ?g/L) promoted tube formation of MSCs. The tubular length reached the maximum of a 2.24-fold increase, when the cells were treated with NGF (50 ?g/L). NGF (50 ?g/L) significantly enhanced Akt phosphorylation. Pretreatment with the specific PI3K inhibitor LY294002 (10 ?mol/L) blocked NGF-stimulated Akt phosphorylation, tube formation and angiogenesis. NGF (25–200 ?g/L) did not affect the expression of TrkA and vascular endothelial growth factor (VEGF), but significantly suppressed the expression of p75NTR. NGF (50 ?g/L) markedly increased the proliferation of MSCs. Conclusion: NGF promoted proliferation of MSCs and activated the PI3K/Akt signaling pathway, which may be responsible for NGF induction of MSC angiogenesis. PMID:22139028

Wang, Wen-xia; Hu, Xin-yang; Xie, Xiao-jie; Liu, Xian-bao; Wu, Rong-rong; Wang, Ya-ping; Gao, Feng; Wang, Jian-an

2011-01-01

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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

 
 
 
 
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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  

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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

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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

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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

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Nerve growth factor regulates the expression and activity of p33cdk2 and p34cdc2 kinases in PC12 pheochromocytoma cells.  

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In the absence of serum, nerve growth factor (NGF) promotes the survival and differentiation of the PC12 pheochromocytoma cell line. In the presence of serum, NGF acts primarily as a differentiation factor and negative regulator of cell cycling. To investigate NGF control of cell cycling, we have analyzed the regulation of cyclin dependent kinases during PC12 cell differentiation. NGF treatment leads to a reduction in the steady-state protein levels of p33cdk2 and p34cdc2, two key regulators ...

Buchkovich, K. J.; Ziff, E. B.

1994-01-01

25

Development of rat embryonic spinal ganglion cells in damaged nerve.  

Science.gov (United States)

The development of dissociated cells from rat embryonic spinal ganglion after transplantation to damaged nerve of adult animals was studied using immunohistochemical differentiation markers of neural and glial cells. The cell suspension obtained after dissociation of rat embryonic spinal ganglia (embryonic day 15) was injected into the proximal segment of crushed sciatic nerve. The nerve was damaged by ligation for 40 sec. Progenitor cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) before transplantation. BrdU-immunopositive cells were detected in the nerve trunks of recipients on days 1, 21, and 28 after transplantation. Dissociated cells of rat embryonic spinal ganglion (embryonic day 15) survived for at least 4 weeks after transplantation to the nerve and differentiate into NeuN-immunopositive neurons with morphological properties of sensory neurons and satellite cells containing S100 protein. PMID:25257430

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

2014-09-01

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

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

Igor Sladojevic

2006-01-01

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Endoplasmic reticulum calcium signaling in nerve cells  

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

ALEXEI VERKHRATSKY

2004-01-01

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Endoplasmic reticulum calcium signaling in nerve cells  

Scientific Electronic Library Online (English)

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

ALEXEI, VERKHRATSKY.

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A central role for the ERK-signaling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo.  

Science.gov (United States)

Following damage to peripheral nerves, a remarkable process of clearance and regeneration takes place. Axons downstream of the injury degenerate, while the nerve is remodeled to direct axonal regrowth. Schwann cells are important for this regenerative process. "Sensing" damaged axons, they dedifferentiate to a progenitor-like state, in which they aid nerve regeneration. Here, we demonstrate that activation of an inducible Raf-kinase transgene in myelinated Schwann cells is sufficient to control this plasticity by inducing severe demyelination in the absence of axonal damage, with the period of demyelination/ataxia determined by the duration of Raf activation. Remarkably, activation of Raf-kinase also induces much of the inflammatory response important for nerve repair, including breakdown of the blood-nerve barrier and the influx of inflammatory cells. This reversible in vivo model identifies a central role for ERK signaling in Schwann cells in orchestrating nerve repair and is a powerful system for studying peripheral neuropathies and cancer. PMID:22365547

Napoli, Ilaria; Noon, Luke A; Ribeiro, Sara; Kerai, Ajay P; Parrinello, Simona; Rosenberg, Laura H; Collins, Melissa J; Harrisingh, Marie C; White, Ian J; Woodhoo, Ashwin; Lloyd, Alison C

2012-02-23

30

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

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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 (ONT) in mice. Our results demonstrate activation of autopha...

Rodri?guez-muela, N.; Germain, Francisco; Marin?o, G.; Fitze, Patrick S.; Boya Tremoleda, Patricia

2012-01-01

31

GFR?1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling.  

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The ability of cancer cells to invade along nerves is associated with aggressive disease and diminished patient survival rates. Perineural invasion (PNI) may be mediated by nerve secretion of glial cell line-derived neurotrophic factor (GDNF) attracting cancer cell migration through activation of cell surface Ret proto-oncogene (RET) receptors. GDNF family receptor (GFR)?1 acts as coreceptor with RET, with both required for response to GDNF. We demonstrate that GFR?1 released by nerves enhances PNI, even in the absence of cancer cell GFR?1 expression. Cancer cell migration toward GDNF, RET phosphorylation, and MAPK pathway activity are increased with exposure to soluble GFR?1 in a dose-dependent fashion. Dorsal root ganglia (DRG) release soluble GFR?1, which potentiates RET activation and cancer cell migration. In vitro DRG coculture assays of PNI show diminished PNI with DRG from GFR?1(+/-) mice compared with GFR?1(+/+) mice. An in vivo murine model of PNI demonstrates that cancer cells lacking GFR?1 maintain an ability to invade nerves and impair nerve function, whereas those lacking RET lose this ability. A tissue microarray of human pancreatic ductal adenocarcinomas demonstrates wide variance of cancer cell GFR?1 expression, suggesting an alternate source of GFR?1 in PNI. These findings collectively demonstrate that GFR?1 released by nerves enhances PNI through GDNF-RET signaling and that GFR?1 expression by cancer cells enhances but is not required for PNI. These results advance a mechanistic understanding of PNI and implicate the nerve itself as a key facilitator of this adverse cancer cell behavior. PMID:24778213

He, Shuangba; Chen, Chun-Hao; Chernichenko, Natalya; He, Shizhi; Bakst, Richard L; Barajas, Fernando; Deborde, Sylvie; Allen, Peter J; Vakiani, Efsevia; Yu, Zhenkun; Wong, Richard J

2014-05-13

32

[Progress in application of the combination of neural stem cells and Schwann cells for nerve repairing].  

Science.gov (United States)

Neural stem cells (NSCs) and Schwann cells (SCs) both play an important role in the recovery and regeneration of peripheral nerve injury, which makes them become the focus in the field of nerve injury research. SCs provide a suitable microenvironment for the recovery and regeneration of injured peripheral nerve through secreting various cytokines and other related factors, and they can significantly promote the differentiation of NSCs into neurons. Recently with the development of microsurgical technique, using nerve conduits along with NSCs and SCs to bridge nerve stumps so as to repair peripheral nerve injury has now attracted increasing research interest. In this article, we focus on the effects and mechanisms of NSCs and SCs on peripheral nerve injury and regeneration process, and describe the future trend and potential clinical application of the technology combining both two cells and nerve conduits to repair peripheral nerve injury. PMID:25248278

Li, Yu; Yu, Ziwei

2014-07-01

33

Hoxa3 regulates integration of glossopharyngeal nerve precursor cells.  

Science.gov (United States)

In vertebrates, certain Hox genes are known to control cellular identities along the anterior-posterior (A-P) axis in the developing hindbrain. In mouse Hoxa3 mutants, truncation of the glossopharyngeal (IXth) nerve or the fusion of the IXth and vagus (Xth) nerves was reported, although its underlying mechanism is largely unknown. To elucidate the mechanism of the IXth nerve defects, we reexamined the phenotype of Hoxa3 mutant embryos. In Hoxa3 mutants, we observed an abnormal caudal stream of the migrating Hoxa3-expressing neural crest cells at the prospective IXth nerve-forming area. Dorsomedial migration of the placode-derived neuronal precursor cells of the IXth nerve was also affected. Motor neurons at rhombomere 6 (r6), where those of the IXth nerve were positioned, often projected axons to the Xth nerve. In summary, the Hoxa3 gene has crucial roles in ensuring the correct axon projection pattern of all three components of the IXth nerve, i.e., motor neurons and sensory neurons of the proximal and distal ganglia. PMID:11784044

Watari, N; Kameda, Y; Takeichi, M; Chisaka, O

2001-12-01

34

Cat diencephalic neurons with sympathetic nerve-related activity.  

Science.gov (United States)

In a companion paper, we demonstrated that hypothalamic or medial thalamic lesions attenuate the reduction in inferior cardiac postganglionic sympathetic nerve discharge (SND) produced by decerebration in the anesthetized cat [Huang et al., Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R249-R256, 1988]. This raised the possibility that these diencephalic regions contain the cell bodies of neurons that contribute to SND. The current study tested this possibility in cats anesthetized with alpha-chloralose. Spike-triggered averaging of inferior cardiac SND revealed the existence of two types of hypothalamic and medial thalamic neurons with sympathetic nerve-related activity. Recordings were made from the soma-dendritic region of these neurons, since an inflection often appeared on the rising phase of the unit action potential. The activity of type 1 neurons was synchronized to an aperiodic spikelike event in SND, whereas that of type 2 neurons was synchronized to a 2- to 6-Hz rhythmic component. Some of the type 2 neurons but none of the type 1 neurons had cardiac-related activity. Microstimulation at type 1 and type 2 unit recording sites increased SND. Our results are consistent with the possibility that hypothalamic and medial thalamic neurons contribute to the rhythmic and aperiodic components of SND in the anesthetized cat. PMID:3344836

Varner, K J; Barman, S M; Gebber, G L

1988-02-01

35

Early interfaced neural activity from chronic amputated nerves  

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

KshitijaGarde

2009-05-01

36

Early interfaced neural activity from chronic amputated nerves.  

Science.gov (United States)

Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704

Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I

2009-01-01

37

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

International Nuclear Information System (INIS)

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

38

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

Science.gov (United States)

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

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

2014-06-20

39

Differentiated mesenchymal stem cells for sciatic nerve injury.  

Science.gov (United States)

Sciatic nerve injury is common and may cause neurological deficits. Previous studies showed that administration of neurotrophic factors (NTFs), naturally occurring proteins that support the development and survival of neurons, preserved and protected damaged motor neuron in the injured sciatic nerve. We have been successful in converting bone marrow-derived mesenchymal stem cells into astrocyte-like cells that produce and secrete NTFs (NTF(+) cells). These cells demonstrate typical astrocyte morphology, express characteristic astrocyte markers and secrete high levels of NTFs. We have already shown that these cells and their conditioned media can protect neurons in culture and in animal models of neurodegenerative diseases. In the current study we examined whether NTF(+) cells are capable of rescuing motor neurons in a rat sciatic nerve injury model, where the right hind limb sciatic nerve was crushed. Rats were transplanted with NTF(+) cells, MSCs or PBS into the lesion site. In rats injected with the NTF(+) cells motor function was markedly preserved. Moreover, NTF(+) cells significantly inhibited the degeneration of the neuromuscular junctions and preserved the myelinated motor axons. Our findings suggest that autologous therapeutic approach can alleviate signs of sciatic nerve injury and probably other neurological disorders. PMID:21327572

Dadon-Nachum, Michal; Sadan, Ofer; Srugo, Itay; Melamed, Eldad; Offen, Daniel

2011-09-01

40

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

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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?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

 
 
 
 
41

Study of stimulators of DNA synthesis in nerve tissue cells  

International Nuclear Information System (INIS)

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

42

Study of stimulators of DNA synthesis in nerve tissue cells  

Energy Technology Data Exchange (ETDEWEB)

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

Vitvitskii, V.N.

1986-04-10

43

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

44

Electrical stimulation of nerve cells using conductive nanofibrous scaffolds for nerve tissue engineering.  

Science.gov (United States)

Fabrication of scaffolds with suitable chemical, mechanical, and electrical properties is critical for the success of nerve tissue engineering. Electrical stimulation was directly applied to electrospun conductive nanofibrous scaffolds to enhance the nerve regeneration process. In the present study, electrospun conductive nanofibers were prepared by mixing 10 and 15 wt% doped polyaniline (PANI) with poly (epsilon-caprolactone)/gelatin (PG) (70:30) solution (PANI/PG) by electrospinning. The fiber diameter, pore size, hydrophilicity, tensile properties, conductivity, Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy spectra of nanofibers were determined, and the in vitro biodegradability of the different nanofibrous scaffolds was also evaluated. Nanofibrous scaffolds containing 15% PANI was found to exhibit the most balanced properties to meet all the required specifications for electrical stimulation for its enhanced conductivity and is used for in vitro culture and electrical stimulation of nerve stem cells. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and scanning electron microscopy results showed that conductive nanofibrous scaffolds are suitable substrates for the attachment and proliferation of nerve stem cells. Electrical stimulation through conductive nanofibrous PANI/PG scaffolds showed enhanced cell proliferation and neurite outgrowth compared to the PANI/PG scaffolds that were not subjected to electrical stimulation. PMID:19496678

Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Morshed, Mohammad; Nasr-Esfahani, Mohammad Hossein; Ramakrishna, Seeram

2009-11-01

45

[Effect of nitric oxide on viscosity of nerve cell membranes].  

Science.gov (United States)

The influence of nitric oxide on the microviscosity of nerve cell membranes was investigated by resonance Raman (RR) spectroscopy. Changes in membrane viscosity were estimated from the resonance Raman-spectra of carotenoids localized in the axon plasmatic membrane and membranes of subcellular vesicles (cytosomes). For the nerve fibre, the extracellular addition of nitric oxide donor, sodium nitroprusside (0.5 mM), caused an increase in the 1526 cm(-1) band relative half-width and the modification of 1160 cm-1 band structure. Moreover, sodium nitroprusside led to an increase in the I1526/I1160 ratio by 13% in 25 min and a decrease in this ratio by 10% in 50 min. In the case of cytosomes, sodium nitroprusside (0.5 mM) resulted in the reduction of the I1526/I1160 ratio by 8% in 25 and 50 min. It was shown that the neuron rhythmic activity correlated with the I1526/I1160 ratio and cytosome membrane microviscosity. We suppose that nitric oxide causes a conformational transition of carotenoids in the axon plasmatic membrane and the membranes of cytosomes. This process can be due to nitric oxide-induced changes of the membrane microviscosity or potential. PMID:15856987

Ul'ianova, N A; Maksimov, G V; Churin, A A; Rubin, A B

2005-01-01

46

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

International Nuclear Information System (INIS)

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

47

In vitro evaluation of cell-seeded chitosan films for peripheral nerve tissue engineering.  

Science.gov (United States)

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

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

2014-09-01

48

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

Science.gov (United States)

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

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

2014-12-01

49

Tissue engineering the retinal ganglion cell nerve fiber layer.  

Science.gov (United States)

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

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

2013-06-01

50

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

Science.gov (United States)

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. Conditioned medium from stimulated cells increased neurite outgrowth of dorsal root ganglia (DRG) neurons. Similarly, stimulated cells showed an enhanced ability to induce capillary-like tube formation in an in vitro angiogenesis assay. ASC were seeded into a fibrin conduit that was used to bridge a 10?mm rat nerve gap. After 2 weeks, the animals treated with control or stimulated ASC showed an enhanced axon regeneration distance. Stimulated cells evoked more total axon growth. Analysis of regeneration and apoptosis-related gene expression showed that both ASC and stimulated ASC enhanced GAP-43 and activating transcription factor 3 (ATF-3) expression in the spinal cord and reduced c-jun expression in the DRG. Caspase-3 expression in the DRG was reduced by stimulated ASC. Both ASC and stimulated ASC also increased the vascularity of the fibrin nerve conduits. Thus, ASC produce functional neurotrophic and angiogenic factors, creating a more desirable microenvironment for nerve regeneration. PMID:24124760

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

2014-04-01

51

Development of neural crest cells expressing nerve growth factor receptors  

Energy Technology Data Exchange (ETDEWEB)

The present study examines the ontogeny of the nerve growth factor receptor of neural crest cells in vitro and the phenotypic nature of the neural crest cells expressing this receptor. /sup 125/I-NGF binding assays and autoradiographic and immunofluorescence techniques have demonstrated the presence of a subpopulation of quail neural crest cells that express specific NGF receptors after 3-4 days in vitro. This subpopulations represents approximately 28% of the cells in 5-day primary cultures and 30-35% of the cells in secondary cultures; these cells generally exhibited a flattened, phase-dark morphology. Approximately one-third of these cells also labeled with a 2 hr pulse of /sup 3/H thymidine. Catecholamine-containing neural crest cells generally lacked NGF receptors. NGF receptor-positive cells also failed to demonstrate somatostatin-, neuron-specific enolase-, or S-100-like immunoreactivity. Melanocytes do not appear to express NGF receptors. Exogenous nerve growth factor did not influence the morphology or mitotic status of the cells in culture.

Greiner, C.A.

1987-01-01

52

Nano-scale Topographical Studies on the Growth Cones of Nerve Cells using AFM  

Science.gov (United States)

Nerve cells are the fundamental units which are responsible for intercommunication within the nervous system. The neurites, fibrous cable-like extensions for information delivery, of nerve cells are tipped by highly motile sensory structures known as the growth cones which execute important functions; neural construction, decision making and navigation during development and regeneration of the nervous system. The highly dynamic subcomponents of the growth cones are important in neural activity. Atomic Force Microscopy (AFM) is the most powerful microscopy technique which is capable of imaging without conductivity constraint and in liquid media. AFM providing nano-scale topographical information on biological structures is also informative on the physical properties such as: elasticity, adhesion, and softness. This contribution focuses on AFM analysis of the growth cones of the nerve cells removed from the buccal ganglion of Helisoma trivolvis. The results of nano-scale topography and softness analysis on growth cone central domain, filopodia and overlying lamellopodium (veil) are presented. The subcomponents of the growth cones of different nerve cells are compared to each other. The results of the analysis are linked to the mechanical properties and internal molecular density distribution of the growth cones.

Durkaya, Goksel; Zhong, Lei; Rehder, Vincent; Dietz, Nikolaus

2009-11-01

53

Combining acellular nerve allografts with brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone  

Science.gov (United States)

In this study, we chemically extracted acellular nerve allografts from bilateral sciatic nerves, and repaired 10-mm sciatic nerve defects in rats using these grafts and brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells. Experiments were performed in three groups: the acellular nerve allograft bridging group, acellular nerve allograft + bone marrow mesenchymal stem cells group, and the acellular nerve allograft + brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group. Results showed that at 8 weeks after bridging, sciatic functional index, triceps wet weight recovery rate, myelin thickness, and number of myelinated nerve fibers were significantly changed in the three groups. Variations were the largest in the acellular nerve allograft + brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group compared with the other two groups. Experimental findings suggest that chemically extracted acellular nerve allograft combined nerve factor and mesenchymal stem cells can promote the restoration of sciatic nerve defects. The repair effect seen is better than the single application of acellular nerve allograft or acellular nerve allograft combined mesenchymal stem cell transplantation. PMID:25422643

Zhang, Yanru; Zhang, Hui; Zhang, Gechen; Ka, Ka; Huang, Wenhua

2014-01-01

54

Nerve growth factor rapidly stimulates arachidonate metabolism in PC12 cells: potential involvement in nerve fiber growth.  

Science.gov (United States)

Homogenates prepared from pheochromocytoma (PC12) cells that are extending nerve fibers in response to nerve growth factor (NGF) have an increased capacity to metabolize exogenous arachidonate compared with homogenates prepared from cells untreated with NGF. These changes are not a consequence of cell attachment, since they are also seen in NGF-treated PC12 cells grown in suspension and are not found in attached cells grown in the absence of NGF. This NGF-stimulated increase in arachidonate metabolic capacity occurs rapidly and before the extension of nerve fibers. In contrast to NGF, epidermal growth factor does not alter the metabolism of exogenous arachidonate by PC12 cells. Radioimmunoassay of medium from PC12 cultures indicates that intact cells produce and release increased amounts of prostaglandin (PGE) in response to NGF. Drugs that inhibit arachidonate liberation from membrane phospholipids (mepacrine or 4-bromphenacyl bromide) block NGF-stimulated nerve fiber growth by PC12 cells. Selective inhibitors of cyclooxygenase metabolism of arachidonate (indomethacin and aspirin) fail to block growth, but inhibitors of lipoxygenase metabolism (baicalein, BW755, and eicosatetraynoic acid) are potent blockers. In cultures of dorsal root ganglion neurons, inhibitors of arachidonate release (mepacrine, 4-bromphenacyl bromide) or its subsequent metabolism by lipoxygenases (nordihydroquaiaretic acid, eicosatetraynoic acid) also prevent the early morphological events of nerve fiber growth. Our data suggest that NGF rapidly and specifically increases the capacity of PC12 cells to synthesize arachidonate metabolites, and that arachidonate metabolism may be important in nerve fiber growth by both PC12 cells and dorsal root ganglion neurons. PMID:3145981

DeGeorge, J J; Walenga, R; Carbonetto, S

1988-01-01

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Schwann cells and mesenchymal stem cells as promoter of peripheral nerve regeneration  

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The transplantation of primary Schwann cells (SC) has been shown to improve nerve regeneration. However, to monitor the survival of transplanted cells within the host, a stable labelling method is required. The in vitro characteristics of green fluorescent protein labelled SC (GFP SC) and their effects in an in vivo peripheral nerve injury model were investigated.   The GFP-SC were readily visualised ex vivo and stimulated significantly better axonal regeneration compared to controls. Clini...

Mantovani, Maria Cristina

2011-01-01

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

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Transplantation of adipose-derived mesenchymal stem cells (ASCs) induces tissue regeneration by accelerating the growth of blood vessels and nerve. However, mechanisms by which they accelerate the growth of nerve fibers are only partially understood. We used transplantation of ASCs with subcutaneous matrigel implants (well-known in vivo model of angiogenesis) and model of mice limb reinnervation to check the influence of ASC on nerve growth. Here we show that ASCs stimulate the regeneration o...

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

2011-01-01

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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

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Nerve cell response to inhibitors recorded with an aluminum-galliumnitride/galliumnitride field-effect transistor.  

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Experiments based on neuronal cell-transistor couplings were made from some groups during the last years. Pioneering work in this field was carried out by Fromherz and his group (Fromherz, 2003; Schmidtner and Fromherz, 2006). We were interested of the interaction of nerve cells to serine hydrolase inhibitor diisopropylfluorophosphate (DFP), monitored by using an aluminum-galliumnitride/galliumnitride (AlGaN/GaN) electrolyte gate field effect transistor (EGFET). The biocompatibility study of our sensor materials with nerve cells shows a proliferation rate of at least 95%. The inhibitors were added to the medium and the source-drain current of the EGFET was recorded as a function of time. The inhibitor was added to the NG108-15 nerve cells growing directly on the sensor surface, resulting in a fast decrease in the drain current, I(DS). Control measurements show that this response is associated with cationic fluxes pumped through ionic channels present in the cellular membrane. The sensor enables analysis of the ion channel activity without cell destruction and simultaneously allows visual observation due to the optical transparency of the sensor material. PMID:22426140

Gebinoga, Michael; Mai, Patrick; Donahue, Mary; Kittler, Mario; Cimalla, Irina; Lübbers, Benedikt; Klett, Maren; Lebedev, Vadim; Silveira, Liele; Singh, Sukhdeep; Schober, Andreas

2012-01-01

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Active gene repression by the Egr2.NAB complex during peripheral nerve myelination.  

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The Egr2/Krox20 transactivator is required for activation of many myelin-associated genes during peripheral nerve myelination by Schwann cells. However, recent work has indicated that Egr2 not only activates genes required for peripheral nerve myelination but may also be involved in gene repression. The NAB (NGFI-A/Egr-binding) corepressors interact with Egr2 and are required for proper coordination of myelin formation. Therefore, NAB proteins could mediate repression of some Egr2 target genes, although direct repression by Egr2 or NAB proteins during myelination has not been demonstrated. To define the physiological role of NAB corepression in gene repression by Egr2, we tested whether the Egr2.NAB complex directly repressed specific target genes. A screen for NAB-regulated genes identified several (including Id2, Id4, and Rad) that declined during the course of peripheral nerve myelination. In vivo chromatin immunoprecipitation analysis of the myelinating sciatic nerve was used to show developmental association of both Egr2 and NAB2 on the Id2, Id4, and Rad promoters as they were repressed during the myelination process. In addition, NAB2 represses transcription by interaction with the chromodomain helicase DNA-binding protein 4 (CHD4) subunit of the nucleosome remodeling and deacetylase chromatin remodeling complex, and we demonstrate that CHD4 occupies NAB-repressed promoters in a developmentally regulated manner in vivo. These results illustrate a novel aspect of genetic regulation of peripheral nerve myelination by showing that Egr2 directly represses genes during myelination in conjunction with NAB corepressors. Furthermore, repression of Id2 was found to augment activation of Mpz (myelin protein zero) expression. PMID:18456662

Mager, Gennifer M; Ward, Rebecca M; Srinivasan, Rajini; Jang, Sung-Wook; Wrabetz, Lawrence; Svaren, John

2008-06-27

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Role of sympathetic nerve activity in the process of fainting  

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Full Text Available Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery, and the process of syncope progression will be described with two types of sympathetic change. Simultaneous recordings of microneurographically recorded MSNA and continuous and noninvasive blood pressure measurement have disclose what is going on in the course of progression of the syncope. Vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. The vasovagal syncope is characterized by the sympathoexcitation, followed by vagal overcome via the Bezold-Jarisch reflex. Orthostatic syncope is caused by the response failure or lack of sympathetic nerve activity toward the orthostatic challenge followed by the fluid shift, and subsequent cerebral low perfusion. Four causes are considered for the compensatory failure, which triggers the orthostatic syncope; hypovolemia, increased pooling in the lower body, failure to activate the sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions were described in the viewpoint of 1 exaggerated sympathoexcitation and 2 failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control the cardiovascular function, and its failure resulted syncope, however, responses of the system by microneurographically recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism.

SatoshiIwase

2014-09-01

 
 
 
 
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In vivo integration of poly(?-caprolactone)/gelatin nanofibrous nerve guide seeded with teeth derived stem cells for peripheral nerve regeneration.  

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Artificial nanofiber nerve guides have gained huge interest in bridging nerve gaps and associated peripheral nerve regeneration due to its high surface area, flexibility and porous structure. In this study, electrospun poly (?-caprolactone)/gelatin (PCL/Gel) nanofibrous mats were fabricated, rolled around a copper wire and fixed by medical grade adhesive to obtain a tubular shaped bio-graft, to bridge 10 mm sciatic nerve gap in in vivo rat models. Stem cells from human exfoliated deciduous tooth (SHED) were transplanted to the site of nerve injury through the nanofibrous nerve guides. In vivo experiments were performed in animal models after creating a sciatic nerve gap, such that the nerve gap was grafted using (i) nanofiber nerve guide (ii) nanofiber nerve guide seeded with SHED (iii) suturing, while an untreated nerve gap remained as the negative control. In vitro cell culture study was carried out for primary investigation of SHED-nanofiber interaction and its viability within the nerve guides after 2 and 16 weeks of implantation time. Walking track analysis, plantar test, electrophysiology and immunohistochemistry were performed to evaluate functional recovery during nerve regeneration. Vascularization was also investigated by hematoxilin/eosine (H&E) staining. Overall results showed that the SHED seeded on nanofibrous nerve guide could survive and promote axonal regeneration in rat sciatic nerves, whereby the biocompatible PCL/Gel nerve guide with cells can support axonal regeneration and could be a promising tissue engineered graft for peripheral nerve regeneration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4554-4567, 2014. PMID:24677613

Beigi, Mohammad-Hossein; Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Karbalaie, Khadijeh; Azadeh, Hamid; Ramakrishna, Seeram; Baharvand, Hossein; Nasr-Esfahani, Mohammad-Hossein

2014-12-01

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

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

A.K. Sheikhi

2007-01-01

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

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

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

2013-04-01

64

Photodynamic damage of glial cells in crayfish ventral nerve cord  

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

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

2011-03-01

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Nerve growth factor enhances Clara cell proliferation after lung injury.  

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The lung epithelia facilitate wound closure by secretion of various cytokines and growth factors. Nerve growth factor (NGF) has been well described in airway inflammation; however, its likely role in lung repair has not been examined thus far. To investigate the repair function of NGF, experiments were performed in vitro using cultured alveolar epithelial cells and in vivo using a naphthalene-induced model of Clara epithelial cell injury. Both in vitro and in vivo experiments revealed airway epithelial cell proliferation following injury to be dependent on NGF and the expression of its receptor, tropomyosin-receptor-kinase A. Additionally, NGF also augmented in vitro migration of alveolar type II cells. In vivo, transgenic mice over-expressing NGF in Clara cells (NGFtg) did not reveal any proliferation or alteration in Clara cell phenotype. However, following Clara cell specific injury, proliferation was increased in NGFtg and impaired upon inhibition of NGF. Furthermore, NGF also promoted the expression of collagen I and fibronectin in vitro and in vivo during repair, where significantly higher levels were measured in re-epithelialising NGFtg mice. Our study demonstrates that NGF promotes the proliferation of lung epithelium in vitro and the renewal of Clara cells following lung injury in vivo. PMID:20075049

Sonar, S S; Schwinge, D; Kilic, A; Yildirim, A O; Conrad, M L; Seidler, K; Müller, B; Renz, H; Nockher, W A

2010-07-01

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Understanding cochlear function through auditory-nerve activity: A Zwislocki perspective  

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Dr. Joe Zwislocki served as my dissertation advisor during those tumultuous years in cochlear physiology when our understanding of outer hair cell (OHC) function was evolving from that of a sensory cell to that of a mechanical amplifier. Spoendlin had recently demonstrated that 90%-95% of auditory-nerve afferents originated from inner hair cells (IHCs), but the characteristics of IHC receptor potentials remained an enigma. Otoacoustic emissions and OHC electromotility were terms yet to be defined. Theories relating auditory-nerve activity to basilar-membrane mechanics included concepts of second filters, basilar-membrane nonlinearities, and phase opposition. It was a fertile time for theories and experiments attempting to describe a black-box system that did not yield its mysteries easily. Around 1977, IHC receptor potentials were found to be as sharply tuned as auditory-nerve responses, and the era of cochlear micromechanics began. Joe Zwislocki, as usual, has played a primary role in defining this new era, utilizing the relationships between the OHC stereocilia and the tectorial membrane as his modeling clay.

Schmiedt, Richard A.

2003-04-01

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Upregulation of Gem relates to retinal ganglion cells apoptosis after optic nerve crush in adult rats.  

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GTP-binding protein Gem, a member protein of the Ras superfamily, can regulate actin cytoskeleton reorganization mediated by Rho-associated coiled-coil-containing protein kinase (ROCK). One attractive activity of the ROCK is playing a potential role in physiological and pathological process in retinal ganglion cells (RGCs) apoptosis. However, the function of Gem in retina is still with limited understanding. To investigate whether Gem is involved in optic nerve injury, we performed an optic nerve crush (ONC) model in adult rats. Western blot analysis indicated that Gem was significantly increased in the retina at the 3rd day after ONC. Meanwhile, double-immunofluorescent staining showed that Gem expression was mainly up-regulated in ganglion cell layer and co-localized with NeuN (a marker of RGCs). Additionally, the co-localizations of Gem/active-caspase-3 and Gem/TUNEL-positive cells were detected in RGCs. Furthermore, the expression of active-caspase-3 and TUNEL-positive cells was parallel with that of Gem. Finally, expression pattern of ROCK family (only ROCK2 but not ROCK1) was increased in the differentiated process, which was collected with the expression of GEM and active-caspase-3. Based on the present results, it is suggested that Gem might play a crucial role in RGCs apoptosis after ONC, which might be involved in ROCK pathway. PMID:24948002

Xu, Fan; Huang, Hui; Wu, Yu; Lu, Lu; Jiang, Li; Chen, Lifei; Zeng, Siming; Li, Li; Li, Min

2014-10-01

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

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

NickSpencer

2013-10-01

69

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

Science.gov (United States)

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

Travis, Lee; Spencer, Nick J

2013-01-01

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

International Nuclear Information System (INIS)

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

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

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

Takaku, Yasuharu

2014-01-07

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Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration  

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Apoptotic nerve cell death is implicated in the pathogenesis of several devastating neurodegenerative conditions, including glaucoma and Alzheimer's and Parkinson's diseases. We have devised a noninvasive real-time imaging technique using confocal laser-scanning ophthalmoscopy to visualize single nerve cell apoptosis in vivo, which allows longitudinal study of disease processes that has not previously been possible. Our method utilizes the unique optical properties of the eye, which allow direct microscopic observation of nerve cells in the retina. We have been able to image changes occurring in nerve cell apoptosis over hours, days, and months and show that effects depend on the magnitude of the initial apoptotic inducer in several models of neurodegenerative disease in rat and primate. This technology enables the direct observation of single nerve cell apoptosis in experimental neurodegeneration, providing the opportunity for detailed investigation of fundamental disease mechanisms and the evaluation of interventions with potential clinical applications, together with the possibility of taking this method through to patients.

Cordeiro, M. Francesca; Guo, Li; Luong, Vy; Harding, Glen; Wang, Wei; Jones, Helen E.; Moss, Stephen E.; Sillito, Adam M.; Fitzke, Frederick W.

2004-09-01

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Fibrin matrix for suspension of regenerative cells in an artificial nerve conduit.  

Science.gov (United States)

Peripheral nerve injury presents with specific problems of neuronal reconstructions, and from a clinical viewpoint a tissue engineering approach would facilitate the process of repair and regeneration. We have previously used artificial nerve conduits made from bioresorbable poly-3-hydroxybutyrate (PHB) in order to refine the ways in which peripheral nerves are repaired and reconnected to the target muscles and skin. The addition of Schwann cells (SC) or differentiated mesenchymal stem cells (dMSC) to the conduits enhances regeneration. In this study, we have used a matrix based on fibrin (Tisseel) to fill optimally the nerve-conduits with cells. In vitro analysis showed that both SC and MSC adhered significantly better to PHB in the presence of fibrin and cells continued to maintain their differentiated state. Cells were more optimally distributed throughout the conduit when seeded in fibrin than by delivery in growth medium alone. Transplantation of the nerve conduits in vivo showed that cells in combination with fibrin matrix significantly increased nerve regeneration distance (using PGP9.5 and S100 distal and proximal immunohistochemistry) when compared with empty PHB conduits. This study shows the beneficial combinatory effect of an optimised matrix, cells and conduit material as a step towards bridging nerve gaps which should ultimately lead to improved functional recovery following nerve injury. PMID:18218346

Kalbermatten, D F; Kingham, P J; Mahay, D; Mantovani, C; Pettersson, J; Raffoul, W; Balcin, H; Pierer, G; Terenghi, G

2008-06-01

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Implication of Nerve Growth Factor in intestinal mucosal mast cell activity and colonic motor alterations in a model of ovalbumin-induced gut dysfunction in rats  

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We determined NGF involvement in MMCs and colonic motor alterations in an ovalbumin (OVA)-induced gut dysfunction model in rats. Animals received OVA (6 weeks), with/without simultaneous K252a (TrkA antagonist) treatment. MMCs, rat mast cell protease II (RMCPII) levels and colonic contractility in vitro were assessed. OVA increased MMC density and RMCPII concentration. Spontaneous contractility was similar in both groups and inhibited by K252a. Carbachol responses were increased by OVA in a K...

Jardi? Pujol, Ferran

2011-01-01

75

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

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

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

2009-02-18

76

Effect of morphine on sympathetic nerve activity in humans  

Science.gov (United States)

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.

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

2002-01-01

77

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

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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 (ONT) in mice. Our results demonstrate activation of autophagy shortly after axotomy with autophagosome formation, upregulation of the autophagy regulator Atg5 and apoptotic death of 50% of the retinal ganglion cells (RGCs) after 5 days. Genetic downregulation of autophagy using knockout mice for Atg4B (another regulator of autophagy) or with specific deletion of Atg5 in retinal ganglion cells, using the Atg5(flox/flox) mice reduces cell survival after ONT, whereas pharmacological induction of autophagy in vivo increases the number of surviving cells. In conclusion, our data support that autophagy has a cytoprotective role in RGCs after traumatic injury and may provide a new therapeutic strategy to ameliorate retinal diseases. PMID:21701497

Rodríguez-Muela, N; Germain, F; Mariño, G; Fitze, P S; Boya, P

2012-01-01

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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  

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Full Text Available 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 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42
(47.6% cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the staining
was evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression in
hypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerve
axons, and might be a successful target for the implementation of neuroprotective drugs.Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells 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 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42
(47.6% cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the staining
was evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression in
hypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerve
axons, and might be a successful target for the implementation of neuroprotective drugs.

Joanna Resze?

2012-10-01

79

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

International Nuclear Information System (INIS)

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

80

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

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

Komori, S.; Ohashi, H.

1987-01-01

 
 
 
 
81

Nerve growth factor promotes expression of novel genes in intervertebral disc cells that regulate tissue degradation.  

Science.gov (United States)

Object Increased neurotrophin activity in degenerative intervertebral discs (IVDs) is one potential cause of chronic low-back pain (LBP). The aim of the study was to assess if nerve growth factor (NGF) might alter gene expression of IVD cells and contribute to disc degeneration by enhancing expression or activity of factors that cause breakdown of IVD matrix. Methods Rat-tail IVD cells were stimulated by NGF and subjected to microarray analysis. Real-time polymerase chain reaction, Western blotting, and immunocytochemistry of rat and human IVD cells and tissues treated with NGF in vitro in the absence or presence of the NGF inhibitor Ro 08-2750 were used to confirm findings of the microarray studies. Phosphorylation of mitogen-activated protein kinase (MAPK) was used to identify cell signaling pathways involved in NGF stimulation in the absence or presence of Ro 08-2750. Results Microarray analysis demonstrated increased expression of chitinase 3-like 1 (Chi3l1), lipocalin 2 (Lcn2), and matrix metalloproteinase-3 (Mmp3) following NGF stimulation of rat IVD cells in vitro. Increased gene expression was confirmed by real-time polymerase chain reaction with a relative increase in the Mmp/Timp ratio. Increased expression of Chi3l1, Lcn2, and Mmp3 following NGF stimulation was also demonstrated in rat cells and human tissue in vitro. Effects of NGF on protein expression were blocked by an NGF inhibitor and appear to function through the extracellular-regulation kinase 1/2 (ERK1/2) MAPK pathway. Conclusions Nerve growth factor has potential effects on matrix turnover activity and influences the catabolic/anabolic balance of IVD cells in an adverse way that may potentiate IVD degeneration. Anti-NGF treatment might be beneficial to ameliorate progressive tissue breakdown in IVD degeneration and may lead to pain relief. PMID:25062286

Kao, Ting-Hsien; Peng, Yi-Jen; Tsou, Hsi-Kai; Salter, Donald M; Lee, Herng-Sheng

2014-10-01

82

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 R.

1995-05-01

83

Inflammatory stimulation preserves physiological properties of retinal ganglion cells after optic nerve injury.  

Science.gov (United States)

Axonal injury in the optic nerve is associated with retinal ganglion cell (RGC) degeneration and irreversible loss of vision. However, inflammatory stimulation (IS) by intravitreal injection of Pam3Cys transforms RGCs into an active regenerative state enabling these neurons to survive injury and to regenerate axons into the injured optic nerve. Although morphological changes have been well studied, the functional correlates of RGCs transformed either into a de- or regenerating state at a sub-cellular level remain unclear. In the current study, we investigated the signal propagation in single intraretinal axons as well as characteristic activity features of RGCs in a naive, a degenerative or a regenerative state in ex vivo retinae 1 week after either optic nerve cut alone (ONC) or additional IS (ONC + IS). Recordings of single RGCs using high-density microelectrode arrays demonstrate that the mean intraretinal axonal conduction velocity significantly decreased within the first week after ONC. In contrast, when ONC was accompanied by regenerative Pam3Cys treatment the mean intraretinal velocity was undistinguishable from control RGCs, indicating a protective effect on the proximal axon. Spontaneous RGC activity decreased for the two most numerous RGC types (ON- and OFF-sustained cells) within one post-operative week, but did not significantly increase in RGCs after IS. The analysis of light-induced activity revealed that RGCs in ONC animals respond on average later and with fewer spikes than control RGCs. IS significantly improved the responsiveness of the two studied RGC types. These results show that the transformation into a regenerative state by IS preserves, at least transiently, the physiological functional properties of injured RGCs. PMID:24574973

Stutzki, Henrike; Leibig, Christian; Andreadaki, Anastasia; Fischer, Dietmar; Zeck, Günther

2014-01-01

84

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

85

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 R.

1996-01-01

86

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)

87

Influence of Different Geometric Representations of the Volume Conductor on Nerve Activation during Electrical Stimulation  

Science.gov (United States)

Volume conductor models with different geometric representations, such as the parallel layer model (PM), the cylindrical layer model (CM), or the anatomically based model (AM), have been employed during the implementation of bioelectrical models for electrical stimulation (FES). Evaluating their strengths and limitations to predict nerve activation is fundamental to achieve a good trade-off between accuracy and computation time. However, there are no studies aimed at clarifying the following questions. (1) Does the nerve activation differ between CM and PM? (2) How well do CM and PM approximate an AM? (3) What is the effect of the presence of blood vessels and nerve trunk on nerve activation prediction? Therefore, in this study, we addressed these questions by comparing nerve activation between CM, PM, and AM models by FES. The activation threshold was used to evaluate the models under different configurations of superficial electrodes (size and distance), nerve depths, and stimulation sites. Additionally, the influences of the sciatic nerve, femoral artery, and femoral vein were inspected for a human thigh. The results showed that the CM and PM had a high error rate, but the variation of the activation threshold followed the same tendency for electrode size and interelectrode distance variation as AM.

Gomez-Tames, Jose; Gonzalez, Jose; Yu, Wenwei

2014-01-01

88

Early Interfaced Neural Activity from Chronic Amputated Nerves  

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Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive i...

Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I.

2009-01-01

89

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

90

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2002-10-01

91

[Polyclonal antibodies, labeling radial nerve cells of the starfish Asterias amurensis].  

Science.gov (United States)

The results of preliminary studies suggest that the cytoskeletal fraction of the radial nerve of the starfish Asterias amurensis contained a 32 kDa protein, which is tissue specific. This protein was isolated from the radial nerve by preparative electrophoresis and used as an antigen for raising polyclonal antibodies. When testing these antibodies on sections of the starfish tissues, it was shown that they interact only with the proteins present in the radial nerve cells. A conclusion was drawn that the raised antibodies may be used as a cell marker when studying regeneration of the nervous system in starfish. PMID:10780105

Elise?kina, M G; Lamash, N E; Bulgakov, A A; Dolmatov, I Iu

2000-01-01

92

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

93

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

94

Schwann cells originating from skin-derived precursors promote peripheral nerve regeneration in rats.  

Science.gov (United States)

Artificial guidance channels containing Schwann cells can promote the regeneration of injured peripheral nerve over long distances. However, primary Schwann cells are not suitable for autotransplantation. Under specific conditions, skin-derived progenitors can be induced to differentiate into Schwann cells. Therefore, adult rat dorsal skin (dermis)-derived progenitors were isolated and induced to differentiate with DMEM/F12 containing B27, neuregulin 1, and forskolin. Immunofluorescence staining and reverse transcription polymerase chain reaction (RT-PCR) confirmed that the resultant cells were indeed Schwann cells. Artificial guidance channels containing skin-derived progenitors, Schwann cells originating from skin-derived progenitors, or primary Schwann cells were used to bridge 5 mm sciatic nerve defects. Schwann cells originating from skin-derived progenitors significantly promoted sciatic nerve axonal regeneration. The significant recovery of injured rat sciatic nerve function after the transplantation of Schwann cells originating from skin-derived progenitors was confirmed by electromyogram. The therapeutic effect of Schwann cells originating from skin-derived progenitors was better than that of skin-derived progenitors. These findings indicate that Schwann cells originating from skin-derived precursors can promote peripheral nerve regeneration in rats. PMID:25374591

Zhang, Ping; Lu, Xiaocheng; Chen, Jianghai; Chen, Zhenbing

2014-09-15

95

Axon-Schwann cell interactions during peripheral nerve regeneration in zebrafish larvae  

Science.gov (United States)

Background Peripheral nerve injuries can severely affect the way that animals perceive signals from the surrounding environment. While damage to peripheral axons generally has a better outcome than injuries to central nervous system axons, it is currently unknown how neurons re-establish their target innervations to recover function after injury, and how accessory cells contribute to this task. Here we use a simple technique to create reproducible and localized injury in the posterior lateral line (pLL) nerve of zebrafish and follow the fate of both neurons and Schwann cells. Results Using pLL single axon labeling by transient transgene expression, as well as transplantation of glial precursor cells in zebrafish larvae, we individualize different components in this system and characterize their cellular behaviors during the regenerative process. Neurectomy is followed by loss of Schwann cell differentiation markers that is reverted after nerve regrowth. We show that reinnervation of lateral line hair cells in neuromasts during pLL nerve regeneration is a highly dynamic process with promiscuous yet non-random target recognition. Furthermore, Schwann cells are required for directional extension and fasciculation of the regenerating nerve. We provide evidence that these cells and regrowing axons are mutually dependant during early stages of nerve regeneration in the pLL. The role of ErbB signaling in this context is also explored. Conclusion The accessibility of the pLL nerve and the availability of transgenic lines that label this structure and their synaptic targets provides an outstanding in vivo model to study the different events associated with axonal extension, target reinnervation, and the complex cellular interactions between glial cells and injured axons during nerve regeneration. PMID:25326036

2014-01-01

96

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

97

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

International Nuclear Information System (INIS)

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

98

Differential Effects of Chlorthalidone Versus Spironolactone on Muscle Sympathetic Nerve Activity in Hypertensive Patients  

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Context: Previous studies in rats indicated that thiazide-type diuretics reduced blood pressure (BP) and triggered baroreflex-mediated increase in sympathetic nerve activity (SNA), whereas spironolactone exerted central sympathoinhibitory action in addition to diuretic effects.

Menon, Dileep V.; Arbique, Debbie; Wang, Zhongyun; Adams-huet, Beverley; Auchus, Richard J.; Vongpatanasin, Wanpen

2009-01-01

99

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

100

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity.  

Science.gov (United States)

Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs. PMID:25175420

Le Prell, Colleen G; Dolan, David F; Hughes, Larry F; Altschuler, Richard A; Shore, Susan E; Jr, Sanford C Bledsoe

2014-10-17

 
 
 
 
101

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

Science.gov (United States)

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

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

2014-10-01

102

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

103

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.

104

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

International Nuclear Information System (INIS)

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

105

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

Energy Technology Data Exchange (ETDEWEB)

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

Matsuda, Y.; Nakanishi, N.; Dickens, G.; Guroff, G.

1986-05-01

106

Lack of light-induced elevation of renal sympathetic nerve activity and plasma corticosterone levels in PACAP-deficient mice.  

Science.gov (United States)

PACAP is a neurotransmitter involved in the signal transduction of light stimulation in the suprachiasmatic nucleus (SCN). Light stimulation affects autonomic nerve activity via the SCN, and here we tested whether PACAP participates in light-induced regulation of sympatho-adrenal activity by using PACAP-deficient (Adcyap1(-/-)) mice. Light stimulation (100 lux, 30 min) significantly elevated both renal sympathetic nerve activity (RSNA), which was monitored on a digital oscilloscope, and plasma corticosterone levels in wild-type mice, but both responses were almost abolished in Adcyap1(-/-) mice. Although light-induced c-Fos expression in the SCN was observed in both genotypes, the numbers of c-Fos positive cells were significantly decreased in Adcyap1(-/-) mice. These data suggest that PACAP signaling pathway is involved in light-induced stimulation of RSNA and plasma corticosterone release through SCN of brain. PMID:18722505

Hatanaka, Michiyoshi; Tanida, Mamoru; Shintani, Norihito; Isojima, Yasushi; Kawaguchi, Chihiro; Hashimoto, Hitoshi; Kakuda, Michiya; Haba, Ryota; Nagai, Katsuya; Baba, Akemichi

2008-10-24

107

Nerve Growth Factor (NGF) Regulates Activity of Nuclear Factor of Activated T-cells (NFAT) in Neurons via the Phosphatidylinositol 3-Kinase (PI3K)-Akt-Glycogen Synthase Kinase 3? (GSK3?) Pathway.  

Science.gov (United States)

The Ca(2+)/calcineurin-dependent transcription factor nuclear factor of activated T-cells (NFAT) plays an important role in regulating many neuronal functions, including excitability, axonal growth, synaptogenesis, and neuronal survival. NFAT can be activated by action potential firing or depolarization that leads to Ca(2+)/calcineurin-dependent dephosphorylation of NFAT and its translocation to the nucleus. Recent data suggest that NFAT and NFAT-dependent functions in neurons can also be potently regulated by NGF and other neurotrophins. However, the mechanisms of NFAT regulation by neurotrophins are not well understood. Here, we show that in dorsal root ganglion sensory neurons, NGF markedly facilitates NFAT-mediated gene expression induced by mild depolarization. The effects of NGF were not associated with changes in [Ca(2+)]i and were independent of phospholipase C activity. Instead, the facilitatory effect of NGF depended on activation of the PI3K/Akt pathway downstream of the TrkA receptor and on inhibition of glycogen synthase kinase 3? (GSK3?), a protein kinase known to phosphorylate NFAT and promote its nuclear export. Knockdown or knockout of NFATc3 eliminated this facilitatory effect. Simultaneous monitoring of EGFP-NFATc3 nuclear translocation and [Ca(2+)]i changes in dorsal root ganglion neurons indicated that NGF slowed the rate of NFATc3 nuclear export but did not affect its nuclear import rate. Collectively, our data suggest that NGF facilitates depolarization-induced NFAT activation by stimulating PI3K/Akt signaling, inactivating GSK3?, and thereby slowing NFATc3 export from the nucleus. We propose that NFAT serves as an integrator of neurotrophin action and depolarization-driven calcium signaling to regulate neuronal gene expression. PMID:25231981

Kim, Man-Su; Shutov, Leonid P; Gnanasekaran, Aswini; Lin, Zhihong; Rysted, Jacob E; Ulrich, Jason D; Usachev, Yuriy M

2014-11-01

108

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...

Viader, Andreu; Golden, Judith P.; Baloh, Robert H.; Schmidt, Robert E.; Hunter, Daniel A.; Milbrandt, Jeffrey

2011-01-01

109

Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo.  

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Cell-based therapies are increasingly recognized as a potential strategy to treat retinal neurodegenerative disease. Their administration, however, is normally indirect and complex, often with an inability to assess in real time their effects on cell death and their migration/integration into the host retina. In the present study, using a partial optic nerve transection (pONT) rat model, we describe a new method of Schwann cell (SC) delivery (direct application to injured optic nerve sheath, SC/DONS), which was compared with intravitreal SC delivery (SC/IVT). Both SC/DONS and SC/IVT were able to be assessed in vivo using imaging to visualize retinal ganglion cell (RGC) apoptosis and SC retinal integration. RGC death in the pONT model was best fitted to the one-phase exponential decay model. Although both SC/DONS and SC/IVT altered the temporal course of RGC degeneration in pONT, SC/DONS resulted in delayed but long-lasting effects on RGC protection, compared with SC/IVT treatment. In addition, their effects on primary and secondary degeneration, and axonal regeneration, were also investigated, by histology, whole retinal counting, and modelling of RGC loss. SC/DONS was found to significantly reduce RGC apoptosis in vivo and significantly increase RGC survival by targeting secondary rather than primary degeneration. Both SC/DONS and SC/IVT were found to promote RGC axonal regrowth after optic nerve injury, with evidence of GAP-43 expression in RGC somas and axons. SC/DONS may have the potential in the treatment of optic neuropathies, such as glaucoma. We show that SC transplantation can be monitored in real time and that the protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic. PMID:25321467

Guo, L; Davis, B; Nizari, S; Normando, E M; Shi, H; Galvao, J; Turner, L; Shi, J; Clements, M; Parrinello, S; Cordeiro, M F

2014-01-01

110

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

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

Tirone, F.; Shooter, E. M.

1989-01-01

111

Nerve conduction  

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... individual nerve fibers (neurons). Neurons consist of dendrites, axon, and cell body. The dendrites are the tree- ... genetic information in the form of DNA. The axon transmits signals away from the cell body to ...

112

Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways  

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

Adriaenssens Eric

2010-06-01

113

Computation of induced electric field for the sacral nerve activation  

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

114

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

115

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.

Albarracín, A. L.; Farfán, F. D.; Felice, C. J.

2007-11-01

116

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

117

Promoting nerve cell functions on hydrogels grafted with poly(L-lysine).  

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We present a novel photopolymerizable 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 neurons and astrocytes. The role of efficiently controlled substrate stiffness in regulating nerve cell behavior is also investigated and a polymerizable cationic small molecule, [2-(methacryloyloxy)ethyl]-trimethylammonium chloride (MTAC), is used to compare with this newly developed PLL. The results indicate that these PLL-grafted hydrogels are promising biomaterials for nerve repair and regeneration. PMID:22251248

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

2012-02-13

118

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

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

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

2013-12-01

119

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

120

Nerve growth factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by inducing glial cytokine release.  

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Osmotic swelling of neurons and glial cells contributes to the development of retinal edema and neurodegeneration. We show that nerve growth factor (NGF) inhibits the swelling of glial (Müller) and bipolar cells in rat retinal slices induced by barium-containing hypoosmotic solution. NGF also reduced Müller and bipolar cell swelling in the post-ischemic retina. On the other hand, NGF prevented the swelling of freshly isolated Müller cells, but not of isolated bipolar cells, suggesting that NGF induces a release of factors from Müller cells that inhibit bipolar cell swelling in retinal slices. The inhibitory effect of NGF on Müller cell swelling was mediated by activation of TrkA (the receptor tyrosine kinase A), but not p75(NTR) , and was prevented by blockers of metabotropic glutamate, P2Y1 , adenosine A1 , and fibroblast growth factor receptors. Basic fibroblast growth factor fully inhibited the swelling of freshly isolated Müller cells, but only partially the swelling of isolated bipolar cells. In addition, glial cell line-derived neurotrophic factor and transforming growth factor-?1, but not epidermal growth factor and platelet-derived growth factor, reduced the swelling of bipolar cells. Both Müller and bipolar cells displayed TrkA immunoreactivity, while Müller cells were also immunostained for p75(NTR) and NGF. The data suggest that the neuroprotective effect of NGF in the retina is in part mediated by prevention of the cytotoxic glial and bipolar cell swelling. Cytotoxic cell swelling contributes to retinal neurodegeneration. Nerve growth factor (NGF) inhibits the osmotic swelling of glial cells by acting at TrkA, release of bFGF, and opening of K(+) and Cl(-) channels. The NGF-induced glial release of cytokines like bFGF inhibits the osmotic swelling of bipolar cells, suggesting that the neuroprotective effect of NGF is in part mediated by prevention of cytotoxic cell swelling. PMID:25041175

Garcia, Tarcyane Barata; Pannicke, Thomas; Vogler, Stefanie; Berk, Benjamin-Andreas; Grosche, Antje; Wiedemann, Peter; Seeger, Johannes; Reichenbach, Andreas; Herculano, Anderson Manoel; Bringmann, Andreas

2014-11-01

 
 
 
 
121

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

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

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

1985-09-01

122

Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model.  

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Mesenchymal stem cells (MSCs) support axon regeneration across artificial nerve bridges but their differentiative capacity and ability to promote nerve regeneration remains unclear. In this study, MSCs isolated from bone marrow of Sprague-Dawley rats were characterized by plastic adherence and pluripotency towards mesodermal lineages. Isolated undifferentiated MSCs (uMSCs) were stimulated towards a Schwann cell (SC) phenotype using specific growth factors, and cell marker analysis was performed to verify SC phenotype in vitro. Differentiation resulted in temporally dependent positive immunocytochemical staining for the SC markers, glial fibrillary acidic protein (GFAP), S100, and nerve growth factor receptor (NGFR), with maximal marker expression achieved after 6days of treatment with differentiation media. Quantitative analysis demonstrated that ~50% of differentiated MSCs (dMSCs) have a SC phenotype. Using an indirect co-culture system, we compared the ability of dorsal root ganglion (DRG) cells to extend neurites in indirect contact with uMSCs and dMSCs as compared to SCs. The mean values of the longest length of the DRG neurites were the same for the dMSCs and SCs and significantly higher than the uMSC and DRG mono-culture systems (p dMSC seeded collagen nerve conduits resulted in a greater number of sciatic motoneurons regenerating axons through the conduit into the distal nerve stump. We conclude that bone marrow-derived MSCs differentiate into a SC-phenotype that expresses SC markers transiently and sufficiently to support limited neurite outgrowth in vitro and axonal regeneration equivalent to that of SCs in vitro and in vivo. The nerve autograft remains the most effective conduit for supporting regeneration across nerve gaps. PMID:21281630

Ladak, A; Olson, J; Tredget, E E; Gordon, T

2011-04-01

123

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

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

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

2014-04-01

124

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

125

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

126

Natural antibodies against nerve growth factor inhibit in vitro prostate cancer cell metastasis.  

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Prostate cancer is a major cause of death in older men, and bone metastasis is the primary cause of morbidity and mortality in prostate cancer. Prostate is an abundant source of nerve growth factor (NGF) that is secreted by malignant epithelial cells and utilized as an important autocrine factor for growth and metastasis. We previously showed that intravenous gammaglobulin (IVIg) contains natural antibodies against NGF, which inhibit growth and differentiation of the NGF-dependent cell line PC-12. In the present study, we examined the effects of these natural antibodies on in vitro migration or metastasis of two prostate cancer cell lines namely DU-145 and PC-3. Cancer cell migration was assessed using these cell lines in the upper chambers of Matrigel invasion chambers. The effects of IVIg and affinity-purified anti-NGF antibodies on cell migration through membrane into the lower chamber were assessed in dose/response experiments by a colorimetric method. Affinity-purified natural IgG anti-NGF antibody inhibited DU-145 migration by 38% (p = 0.01) and PC-3 migration by 25% (p = 0.02); whereas, a monoclonal anti-NGF antibody inhibited DU-145 migration by 40% (p = 0.01) and PC-3 migration by 37% (p = 0.02), at the same concentration. When IVIg was depleted of NGF-specific IgG by affinity chromatography, there was no significant inhibition of migration of the DU-145 and PC-3 cells at a concentration of 1 mg/well. Removal of the NGF-specific antibody from the IVIg was also demonstrated by a lack of effect on PC-12 cell differentiation. Therefore, IVIg is able to inhibit the migration of prostate cancer cell lines, through Matrigel chambers in vitro, only when the natural NGF-specific antibodies actively are present in IVIg. PMID:20976447

Warrington, Richard J; Lewis, Keith E

2011-02-01

127

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

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

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

2007-12-15

128

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 R.; Walker, D. M.

1997-05-01

129

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

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Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity. PMID:25071459

Sedlacek, Miloslav; Brenowitz, Stephan D

2014-01-01

130

Effects of histamine inhalation and airway vibration on phrenic nerve activity in rabbits.  

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Experiments were performed on 8 rabbits under urethane-chloralose anesthesia. Histamine aerosol (5%) administered into the trachea by a cannula produced tonic activity of the phrenic nerve, with discharges also being evident during the expiratory phase. Airway vibration (100 Hz) inhibited this tonic activity and caused silence during the expiratory phase. PMID:6483284

Homma, I; Onimaru, H; Oouchi, M

1984-07-27

131

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

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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

132

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

133

Reduced spinal microglial activation and neuropathic pain after nerve injury in mice lacking all three nitric oxide synthases  

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Full Text Available Abstract Background Several studies have investigated the involvement of nitric oxide (NO in acute and chronic pain using mice lacking a single NO synthase (NOS gene among the three isoforms: neuronal (nNOS, inducible (iNOS and endothelial (eNOS. However, the precise role of NOS/NO in pain states remains to be determined owing to the substantial compensatory interactions among the NOS isoforms. Therefore, in this study, we used mice lacking all three NOS genes (n/i/eNOS-/-mice and investigated the behavioral phenotypes in a series of acute and chronic pain assays. Results In a model of tissue injury-induced pain, evoked by intraplantar injection of formalin, both iNOS-/-and n/i/eNOS-/-mice exhibited attenuations of pain behaviors in the second phase compared with that in wild-type mice. In a model of neuropathic pain, nerve injury-induced behavioral and cellular responses (tactile allodynia, spinal microglial activation and Src-family kinase phosphorylation were reduced in n/i/eNOS-/-but not iNOS-/-mice. Tactile allodynia after nerve injury was improved by acute pharmacological inhibition of all NOSs and nNOS. Furthermore, in MG-5 cells (a microglial cell-line, interferon-? enhanced NOSs and Mac-1 mRNA expression, and the Mac-1 mRNA increase was suppressed by L-NAME co-treatment. Conversely, the NO donor, sodium nitroprusside, markedly increased mRNA expression of Mac-1, interleukin-6, toll-like receptor 4 and P2X4 receptor. Conclusions Our results provide evidence that the NOS/NO pathway contributes to behavioral pain responses evoked by tissue injury and nerve injury. In particular, nNOS may be important for spinal microglial activation and tactile allodynia after nerve injury.

Shimokawa Hiroaki

2011-07-01

134

Axon-Schwann cell interaction in degenerating and regenerating peripheral nerve  

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

135

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

136

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

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

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

2014-11-01

137

Nerve growth factor receptor signaling in proliferation of normal adult rat chromaffin cells.  

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Adult rat chromaffin cells may proliferate or extend neurites when stimulated by nerve growth factor (NGF) but their response is predominantly proliferative, making them a unique model for studying how mitogenic specificity is achieved. We examined contributions of the NGF receptors trk and p75 and of the major NGF signaling pathways to proliferation versus neurite outgrowth. The type of initial NGF response does not correlate with intensity of immunoreactivity for trk or p75. However, proliferation is initiated at lower NGF concentrations than neurite outgrowth, suggesting that it requires a less intense signal. Mitogenic cooperativity between receptors at low NGF concentrations is suggested by inhibitory effects of p75-blocking antibodies, but responses to trk-agonist antibody indicate that trk activation alone can induce proliferation. NGF-induced phosphorylation of ras-mediated mitogen-activated protein kinases (MAPK) Erk1 and Erk2 is as prolonged in normal chromaffin cells as in PC12 cells, where NGF is neuritogenic. Trk-agonist antibody, which is as mitogenic as NGF but less neuritogenic, causes equally prolonged but less intense ERK phosphorylation. The MAPK kinase(MEK-1) inhibitor PD98059 partially inhibits Erk phosphorylation and does not inhibit chromaffin cell proliferation, while depolarization selectively inhibits proliferation without blocking Erk phosphorylation. Proliferation is markedly reduced by the phosphoinositol-3 (PI-3) kinase inhibitor LY294002 while downregulation of protein kinase C (PKC) causes no change. These findings suggest that low-level, rather than short-duration, stimulation of NGF signaling pathways causes NGF to be mitogenic. Ras-mediated MAPK activation may be more critical in neurite outgrowth than in proliferation and PI-3 kinase may be the major mitogenic determinant. PMID:9931350

Powers, J F; Shahsavari, M; Tsokas, P; Tischler, A S

1999-01-01

138

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

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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

139

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

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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 (Pvivo preclinical study. PMID:24503165

Sedaghati, Tina; Jell, Gavin; Seifalian, Alexander

2014-05-25

140

Involvement of upregulated SYF2 in Schwann cell differentiation and migration after sciatic nerve crush.  

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SYF2 is a putative homolog of human p29 in Saccharomyces cerevisiae. It seems to be involved in pre-mRNA splicing and cell cycle progression. Disruption of SYF2 leads to reduced ?-tubulin expression and delayed nerve system development in zebrafish. Due to the potential of SYF2 in modulating microtubule dynamics in nervous system, we investigated the spatiotemporal expression of SYF2 in a rat sciatic nerve crush (SNC) model. We found that SNC resulted in a significant upregulation of SYF2 from 3 days to 1 week and subsequently returned to the normal level at 4 weeks. At its peak expression, SYF2 distributed predominantly in Schwann cells. In addition, upregulation of SYF2 was approximately in parallel with Oct-6, and numerous Schwann cells expressing SYF2 were Oct-6 positive. In vitro, we observed enhanced expression of SYF2 during the process of cyclic adenosine monophosphate (cAMP)-induced Schwann cell differentiation. SYF2-specific siRNA-transfected Schwann cells did not show significant morphological change in the process of Schwann cell differentiation. Also, we found shorter and disorganized microtubule structure and a decreased migration in SYF2-specific siRNA-transfected Schwann cells. Together, these findings indicated that the upregulation of SYF2 was associated with Schwann cell differentiation and migration following sciatic nerve crush. PMID:24962097

Zhou, Zhengming; Liu, Yang; Nie, Xiaoke; Cao, Jianhua; Zhu, Xiaojian; Yao, Li; Zhang, Weidong; Yu, Jiang; Wu, Gang; Liu, Yonghua; Yang, Huiguang

2014-10-01

 
 
 
 
141

Bone marrow cells are able to increase vessels number during repair of sciatic nerve lesion.  

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The aim of this study was to compare the outcomes of nerve autografts (GRF) and venous grafts containing mononuclear bone marrow cells (BMCs) in sciatic nerve-lesioned rats. Control animals underwent sham operations (SHAM), received empty venous grafts (EPV), or received venous grafts containing BMC vehicle (AGR). Outcome was evaluated through sciatic functional index (SFI), morphometric and morphologic analyses of the nerve distal to the lesion, and the number of spinal cord motor neurons positive for the retrograde tracer, Fluoro-Gold. All groups exhibited poor results in SFI when compared to SHAM animals throughout the postoperative period. All groups also had a significantly greater fiber density, decreased fiber diameter, and decreased motor neuron number than the SHAM group. No significant difference between the GRF and BMC groups was observed in any of these parameters. On the other hand, vessel density was significantly higher in BMC than all other groups. BMC-containing venous grafts are superior to nerve autografts in increasing vessel density during sciatic nerve regeneration. PMID:18241927

Fernandes, Marcela; Valente, Sandra Gomes; Fernandes, Maria José da Silva; Félix, Evandro Penteado Villar; Mazzacoratti, Maria da Graça Naffah; Scerni, Débora Amado; dos Santos, João Baptista Gomes; Leite, Vilnei Mattioli; Faloppa, Flávio

2008-05-15

142

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

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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

143

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

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

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

2014-01-01

144

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

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

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

2014-01-01

145

Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.  

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

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

2014-01-01

146

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

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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

147

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 period (n = 5). Baroreceptor activity was only transiently inhibited after selective stimulation of A-fibers. The inhibition of activity after antidromic stimulation of A and C fibers was prolonged after administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg, IV, n = 7) and abolished after administration of PEG-catalase (104 units/kg, IV, n = 7), an enzyme that catalyzes the decomposition of H2O2 to water and oxygen. The results demonstrate a long-lasting inhibition of baroreceptor activity after antidromic stimulation of 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

148

Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression  

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

Al-Ardati, Hosam; Baeesa, Saleh S.

2014-01-01

149

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

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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

150

Phase-based probabilistic active contour for nerve detection in ultrasound images for regional anesthesia.  

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Ultrasound guided regional anesthesia (UGRA) is steadily growing in popularity, owing to advances in ultrasound imaging technology and the advantages that this technique presents for safety and efficiency. The aim of this work is to assist anaesthetists during the UGRA procedure by automatically detecting the nerve blocks in the ultrasound images. The main disadvantage of ultrasound images is the poor quality of the images, which are also affected by the speckle noise. Moreover, the nerve structure is not salient amid the other tissues, which makes its detection a challenging problem. In this paper we propose a new method to tackle the problem of nerve zone detection in ultrasound images. The method consists in a combination of three approaches: probabilistic, edge phase information and active contours. The gradient vector flow (GVF) is adopted as an edge-based active contour. The phase analysis of the monogenic signal is used to provide reliable edges for the GVF. Then, a learned probabilistic model reduces the false positives and increases the likelihood energy term of the target region. It yields a new external force field that attracts the active contour toward the desired region of interest. The proposed scheme has been applied to sciatic nerve regions. The qualitative and quantitative evaluations show a high accuracy and a significant improvement in performance. PMID:25016592

Hafiane, Adel; Vieyres, Pierre; Delbos, Alain

2014-09-01

151

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

152

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

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

Schlamp Cassandra L

2007-03-01

153

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

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

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

2014-04-30

154

A Combination of Schwann-Cell Grafts and Aerobic Exercise Enhances Sciatic Nerve Regeneration  

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Background Despite the regenerative potential of the peripheral nervous system, severe nerve lesions lead to loss of target-organ innervation, making complete functional recovery a challenge. Few studies have given attention to combining different approaches in order to accelerate the regenerative process. Objective Test the effectiveness of combining Schwann-cells transplantation into a biodegradable conduit, with treadmill training as a therapeutic strategy to improve the outcome of repair after mouse nerve injury. Methods Sciatic nerve transection was performed in adult C57BL/6 mice; the proximal and distal stumps of the nerve were sutured into the conduit. Four groups were analyzed: acellular grafts (DMEM group), Schwann cell grafts (3×105/2 µL; SC group), treadmill training (TMT group), and treadmill training and Schwann cell grafts (TMT + SC group). Locomotor function was assessed weekly by Sciatic Function Index and Global Mobility Test. Animals were anesthetized after eight weeks and dissected for morphological analysis. Results Combined therapies improved nerve regeneration, and increased the number of myelinated fibers and myelin area compared to the DMEM group. Motor recovery was accelerated in the TMT + SC group, which showed significantly better values in sciatic function index and in global mobility test than in the other groups. The TMT + SC group showed increased levels of trophic-factor expression compared to DMEM, contributing to the better functional outcome observed in the former group. The number of neurons in L4 segments was significantly higher in the SC and TMT + SC groups when compared to DMEM group. Counts of dorsal root ganglion sensory neurons revealed that TMT group had a significant increased number of neurons compared to DMEM group, while the SC and TMT + SC groups had a slight but not significant increase in the total number of motor neurons. Conclusion These data provide evidence that this combination of therapeutic strategies can significantly improve functional and morphological recovery after sciatic injury. PMID:25333892

Souto, Allana; Oliveira, Julia Teixeira; de Lima, Silmara; Tonda-Turo, Chiara; Marques, Suelen Adriani; de Almeida, Fernanda Martins; Martinez, Ana Maria Blanco

2014-01-01

155

Phoneutria nigriventer spider venom activates 5-HT4 receptors in rat-isolated vagus nerve.  

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1. The venom of Phoneutria nigriventer spider (PNV) causes intense pain and inflammation following an attack. We have investigated the involvement of capsaicin-sensitive nerve fibres by utilizing an in vitro nerve preparation. Extracellular DC potential recordings were made from the rat-isolated vagus nerve, a preparation that is rich in capsaicin-sensitive, that is, nociceptive, C-fibres. 2. PNV (1-10 microg ml(-1)), capsaicin (0.03-0.3 microM) or 5-hydroxytriptamine (5-HT) (0.3-3 microM) induced dose-dependent depolarizations of vagus nerve fibres. Depolarizing responses to capsaicin were blocked by ruthenium red (RR, 10 microM), but responses to PNV were not. Depolarizing responses to PNV or veratridine (50 microM) were inhibited by tetrodotoxin (TTX, 10 microM), but those to capsaicin were not. This suggests that capsaicin and PNV depolarize the nerve fibres by distinct mechanisms. 3. Depolarization in response to 5-HT (3 microM) was reduced by the 5-HT(3) receptor antagonists Y25130 (0.5 micro M) and tropisetron (10 nM) or, to a lesser extent, by the 5-HT(4) receptor antagonist RS39604 (1 or 10 microM). Depolarizing responses to PNV were not affected significantly by Y25130 or tropisetron, but were blocked by RS39604. 4. These data show that 5-HT(4) receptors play a significant role in the activation of nociceptive sensory nerve fibres by PNV and suggest that this is of importance in the development of the pain and inflammation associated with bites from the P. nigriventer spider. PMID:12746223

Costa, Soraia K P; Brain, Susan D; Antunes, Edson; De Nucci, Gilberto; Docherty, Reginald J

2003-05-01

156

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

157

The ultrastructure of glia-like cells in lateral nerve cords of adult Amphilina foliacea (Amphilinida).  

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The ultrastructure of main lateral nerve cords (MCs) of adult A. foliacea was studied. By examination of the serial sections it has been found that some glia-like cells are located on a periphery of MC. The processes of glia-like cells surround MCs and penetrate into the cord and surround the group of adjacent axons and pairs of neurones. There is a fine extracellular matrix between processes of glia-like cells. The numerous tight junctions occur between processes. The difference between the perykaryon's cytoplasm of glia-like cells in anterior, posterior and central part of MCs was found. PMID:11034168

Biserova, N M

2000-01-01

158

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

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

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

1983-01-01

159

Up-regulation of SKIP relates to retinal ganglion cells apoptosis after optic nerve crush in vivo.  

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Cell cycle re-entry is one of the key processes in neuronal apoptosis. Previous studies have shown that Ski-interacting protein (SKIP) played an important role in cell cycle re-entry. However, its expression and function in optic nerve injury are still with limited acquaintance. To investigate whether SKIP is involved in retinal ganglion cells (RGCs) death, we performed an optic nerve crush (ONC) model in adult rats. Western blot analysis revealed that up-regulation of SKIP was present in retina at 5 days after ONC. Immunofluorescent labeling indicated that up-regulated SKIP was found mainly in RGCs. We also investigated co-localization of SKIP with active-caspase-3 and TUNEL (apoptotic markers) -positive cells in the retina after ONC. In addition, the expression of SKIP was increased in parallel with P53 and P21 in retina after ONC. All these results suggested that up-regulation of SKIP in the retina was associated with RGCs death after ONC. PMID:25074585

Wu, Yu; Xu, Fan; Huang, Hui; Chen, Lifei; Wen, Meidan; Jiang, Li; Lu, Lu; Li, Li; Song, Di; Zeng, Siming; Li, Li; Li, Min

2014-12-01

160

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

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

Thorek, Daniel L.

 
 
 
 
161

Axon-Schwann cell interaction in degenerating and regenerating peripheral nerve  

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Severance of a peripheral nerve stimulates a characteristic sequence of events in the distal stump, including the dissolution of axons and myelin and the proliferation of Schwann cells within their basal lamina. The first part of this thesis employs the cat tibial nerve to examine the relationship between the spatio-temporal pattern of Schwann cell mitosis, loss of the structural and functional properties of axolemma, synthesis of P/sub 0/, the major myelin glycoprotein, and the clearance of morphological myelin. Induction of S phase was measured by determining the uptake of /sup 3/H thymidine into trichloroacetic acid (TCA) precipitates following a 3 hour in vitro incubation in Krebs-Ringers buffer containing /sup 3/H thymidine. Nerve transection stimulated a monophasic increase in /sup 3/H thymidine uptake that peaked at 4 days post-transection throughout an 80 mm length of distal stump. Light microscope autoradiography revealed prominent incorporation into Schwann cells of myelinated fibers. Nerve transection also produced dramatic changes in the intrafascicular binding of /sup 3/H STX which binds to voltage-sensitive sodium channels STX binding fell precipitously to 20% of normal at 4 days post-transection, concurrent with the peak of /sup 3/H thymidine uptake. In conclusion, these studies suggest: (a) Schwann cells divide more or less contemporaneously throughout the distal stump; (b) changes in axons rather than myelin are likely to stimulate the Schwann cell to divide; (c) mitosis regulates other events during Wallerian degeneration, including myelin degeneration and the clearance of sodium channels from nodal axolemma.

Pellegrino, R.G.

1984-01-01

162

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

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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

163

Nerve growth factor reduces amiloride-sensitive Na+ transport in human airway epithelial cells.  

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Nerve growth factor (NGF) is overexpressed in patients with inflammatory lung diseases, including virus infections. Airway surface liquid (ASL), which is regulated by epithelial cell ion transport, is essential for normal lung function. No information is available regarding the effect of NGF on ion transport of airway epithelium. To investigate whether NGF can affect ion transport, human primary air-interface cultured epithelial cells were placed in Ussing chambers to obtain transepithelial voltage (-7.1 ± 3.4 mV), short-circuit current (Isc, 5.9 ± 1.0 ?A), and transepithelial resistance (750 ?·cm(2)), and to measure responses to ion transport inhibitors. Amiloride (apical, 3.5 × 10(-5) mol/L) decreased Isc by 55.3%. Apically applied NGF (1 ng/mL) reduced Isc by 5.3% in 5 min; basolaterally applied NGF had no effect. The response to amiloride was reduced (41.6%) in the presence of NGF. K-252a (10 nmol/L, apical) did not itself affect Na(+) transport, but it attenuated the NGF-induced reduction in Na(+) transport, indicating the participation of the trkA receptor in the NGF-induced reduction in Na(+) transport. PD-98059 (30 ?mol/L, apical and basolateral) did not itself affect Na(+) transport, but attenuated the NGF-induced reduction in Na(+) transport, indicating that trkA activated the Erk 1/2 signaling cascade. NGF stimulated phosphorylation of Erk 1/2 and the ?-subunit of ENaC. K-252a and PD-98059 inhibited these responses. NGF had no effect on Isc in the presence of apical nystatin (50 ?mol/L). These results indicate that NGF inhibits Na(+) transport through a trkA-Erk 1/2-activated signaling pathway linked to ENaC phosphorylation. PMID:25347857

Shimko, Michael J; Zaccone, Eric J; Thompson, Janet A; Schwegler-Berry, Diane; Kashon, Michael L; Fedan, Jeffrey S

2014-01-01

164

Impaired rodent vagal nerve sodium-potassium-ATPase activity in streptozotocin diabetes.  

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Experimental diabetes in rodents is associated with diminished activity of sodium-potassium-adenosine triphosphatase (Na+ -K+ -ATPase) in the sciatic nerve, an abnormality that has been invoked as being factorial in the genesis of diabetic peripheral neuropathy. Whether a parallel metabolic abnormality occurs in the autonomic vagus nerve is unknown. To answer this question, adult male rats made diabetic with streptozotocin (45 mg/kg) and age-matched nondiabetic controls were killed at 1 and 3 months after induction of diabetes. The cervical vagi and sciatic nerves were excised, weighed, and homogenized, and Na+ -K+ -ATPase activities were determined. After 1 month, the diabetic animals showed a significantly reduced sciatic nerve Na+ -K+ -ATPase activity as compared with respective controls, whether expressed in micromoles per gram wet weight per hour (20.5 +/- 4.9 [mean +/- SEM] vs 61.6 +/- 13.0) or micromoles per milligram of protein per hour (0.77 +/- 0.21 vs 2.48 +/- 0.57, p < 0.05, diabetic vs control, respectively). Diabetic vagus nerve Na+ -K+ -ATPase activity was also diminished (40.6 +/- 6.9 mumol/gm wet weight per hour vs 63.2 +/- 9.7 mumol/gm wet weight per hour and 3.83 +/- 0.81 mumol/mg protein per hour vs 5.86 +/- 0.73 mumol/mg protein per hour), but the results did not reach statistical significance. After 3 months, diabetic sciatic nerve Na+ -K+ -ATPase activity was still significantly less than the control group value (16.89 +/- 3.91 mumol/mg wet weight per hour vs 38.9 +/- 4.24 mumol/gm wet weight per hour and 0.48 +/- 0.11 mumol/mg protein per hour vs 1.04 +/- 0.14 mumol/mg protein per hour; p < 0.05, diabetic vs control, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7844468

Nowak, T V; Castelaz, C; Ramaswamy, K; Weisbruch, J P

1995-02-01

165

Electrically evoked auditory nerve responses in the cochlea with normal outer hair cells  

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As hybrid cochlear implant devices are increasingly used for restoring hearing in patients with residual hearing it is important to understand electrically evoked responses in cochleae having functional hair cells. To test the hypothesis that extracochlear electrical stimulation (EES) from sinusoidal current can provoke an auditory nerve response with normal frequency selectivity, the EES-evoked compound action potential (ECAP) was investigated in this study. Brief sinusoidal electrical curre...

Ren, Tianying; Guo, Menghe; He, Wenxuan; Miller, Josef M.; Nuttall, Alfred L.

2009-01-01

166

Granular Cell Tumor of the Ulnar Nerve: MR Neurography Characterization  

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The authors report an unusual case of ulnar neuropathy caused by granular cell tumor. The report describes the anatomic 3 Tesla MR Neurography and functional diffusion tensor findings of the case, which was subsequently confirmed on surgical excision and histopathology. PMID:25426230

Wadhwa, Vibhor; Salaria, Safia N; Chhabra, Avneesh

2014-01-01

167

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

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

João G Franca

2014-10-01

168

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

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

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

2014-01-01

169

Spinal cord stimulation (scs) improves decreased physical activity induced by nerve injury.  

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Spinal cord stimulation (SCS) is used to manage treatment of neuropathic pain to reduce pain and hyperalgesia and to improve activity. Prior studies using animal models of neuropathic pain have shown that SCS reduces hyperalgesia; however, it is unclear whether SCS affects physical activity. Therefore, we tested whether nerve injury (spared nerve injury [SNI] model) reduced physical activity levels, and whether SCS could restore these decreased activity levels. We tested whether SCS given over a long duration (6 hr daily for 3 months) remained effective. We compared SNI with uninjured controls over 4 weeks, and SNI with sham SCS with SNI with active SCS (4 or 60 Hz at 90% motor threshold). We confirmed the presence of mechanical hyperalgesia by examining mechanical thresholds of the paw with von Frey filaments. Physical activity levels were monitored over 30 min in an automated activity chamber as follows: overall activity, distance traveled, grooming behaviors, and rearing. Measures were taken during SCS every 1-2 weeks for 3 months. Animals with SNI (and no or sham SCS) showed decreased withdrawal thresholds ipsilaterally and reduced physical activity (rearing, distance, lines crossed) for 3 months. Both 4- and 60-Hz SCS increased paw withdrawal threshold during and immediately after SCS through 3 months. Both 4- and 60-Hz SCS increased the overall activity (lines crossed), distance traveled, and rearing, but not grooming behaviors for 3 months. This effect remained similar across the 3 months. Thus, measurement of spontaneous physical activity could be useful to examine nocifensive behaviors after nerve injury and is sensitive to SCS. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:24911318

Sato, Karina L; Johanek, Lisa M; Sanada, Luciana S; Sluka, Kathleen A

2014-10-01

170

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

171

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

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

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

2013-10-01

172

Reduced motor nerve conduction velocity and Na(+)-K(+)-ATPase activity in rats maintained on L-fucose diet. Reversal by myo-inositol supplementation.  

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L-Fucose is a monosaccharide that occurs in low concentrations in normal serum but has been shown to be increased in diabetic individuals. In cultured mammalian cells, L-fucose is a potent competitive inhibitor of myo-inositol transport. Abnormal myo-inositol metabolism has been proposed to be a factor in the development of diabetic complications. To test the hypothesis that myo-inositol deficiency may be responsible for the electrophysiological and biological defects in diabetic neuropathy, rats were fed a diet containing 10 or 20% L-fucose for a period of 6 wk. After 3 wk, the L-fucose diets in two groups of rats were supplemented with 1% myo-inositol. At the end of the study protocol, motor nerve conduction velocity, sciatic nerve tissue Na(+)-K(+)-ATPase activity, and myo-inositol content were determined. These results were compared with those of STZ-induced diabetic rats fed either a normal diet or a diet containing 1% myo-inositol or with those given 450 mg/kg body wt of sorbinil. Serum L-fucose levels were significantly increased in rats fed a diet containing 10 or 20% L-fucose. In comparison, the serum L-fucose levels in the diabetic rats were increased to a lesser extent. Motor nerve conduction velocity was significantly slower in rats fed a 10 or 20% L-fucose diet. Sciatic nerve composite and ouabain-sensitive Na(+)-K(+)-ATPase activity and myo-inositol content was also significantly decreased. Supplementation of 1% myo-inositol to the L-fucose-containing diet restored nerve myo-inositol levels and significantly improved Na(+)-K(+)-ATPase activity and motor nerve conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8397126

Yorek, M A; Wiese, T J; Davidson, E P; Dunlap, J A; Stefani, M R; Conner, C E; Lattimer, S A; Kamijo, M; Greene, D A; Sima, A A

1993-10-01

173

SMN Requirement for Synaptic Vesicle, Active Zone and Microtubule Postnatal Organization in Motor Nerve Terminals  

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Low levels of the Survival Motor Neuron (SMN) protein produce Spinal Muscular Atrophy (SMA), a severe monogenetic disease in infants characterized by muscle weakness and impaired synaptic transmission. We report here severe structural and functional alterations in the organization of the organelles and the cytoskeleton of motor nerve terminals in a mouse model of SMA. The decrease in SMN levels resulted in the clustering of synaptic vesicles (SVs) and Active Zones (AZs), reduction in the size...

Torres-benito, Laura; Neher, Margret Feodora; Cano, Raquel; Ruiz, Rocio; Tabares, Lucia

2011-01-01

174

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

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

Gao Li-Zhi

2009-12-01

175

Palmitic and stearic fatty acids induce caspase-dependent and -independent cell death in nerve growth factor differentiated PC12 cells  

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Apoptotic cell death has been proposed to play a role in the neuronal loss observed following traumatic injury in the CNS and PNS. The present study uses an in vitro tissue culture model to investigate whether free fatty acids (FFAs), at concentrations comparable to those found following traumatic brain injury, trigger cell death. Nerve growth factor (NGF)-differentiated PC12 cells exposed to oleic and arachidonic acids (2 : 1 ratio FFA/BSA) showed normal cell survival. However, when cells were exposed to stearic and palmitic acids, there was a dramatic loss of cell viability after 24 h of treatment. The cell death induced by stearic acid and palmitic acid was apoptotic as assessed by morphological analysis, and activation of caspase-8 and caspase-3-like activities. Western blotting showed that differentiated PC12 cells exposed to stearic and palmitic acids exhibited the signature apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP). Interestingly, blockade of caspase activities with the pan-caspase inhibitor z-VAD-fmk failed to prevent the cell death observed induced by palmitic or stearic acid. RT-PCR and RNA blot experiments showed an up-regulation of the Fas receptor and ligand mRNA. These findings are consistent with our hypothesis that FFAs may play a role in the cell death associated with trauma in the CNS and PNS. PMID:12562510

Ulloth, Joel E.; Casiano, Carlos A.; De Leon, Marino

2014-01-01

176

Response of mammalian nerve cells to low-level radiation  

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In experiments with rat brain slices it was shown that a radiation-induced short-term increase in spontaneous neutron activity was mainly a function of dose rate. Pulsed X-radiation (pulse length of 2·10-8 s, doses of 3·10-5 to 6·10-4 Gy) caused the most pronounced reactions that were almost completely prevented by caffeine, euphylline, and norepinephrine (10-4 to 10-3 M)

177

Rapid structural changes in nerve fibers and cells associated with their excitation processes.  

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In a variety of nerve fibers, cells and other excitable tissues, the electric responses to electric stimuli were found to be accompanied by a transient swelling of the tissues. The rising phase of this swelling coincides with that of the electric response. By use of a heat-sensor made of polyvinylidene fluoride film, it was also shown that the electric responses of many types of excitable tissues are accompanied by simultaneous heat production. To elucidate the origin of this swelling and heat production, the process of Ca2+-Na+ exchange in synthetic anionic gel beads and rods was investigated. It is asserted that the observed signs of nerve excitation are manifestations of a rapid structural change of the cortical gel layer of the protoplasm, plasmalemma-ectoplasm complex. The importance of the rapid movement and rearrangement of water molecules in the cortical gel layer in association with excitation processes is emphasized. PMID:10393347

Tasaki, I

1999-04-01

178

Nerve growth factor nonresponsive pheochromocytoma cells: altered internalization results in signaling dysfunction  

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Variant rat pheochromocytoma (PC12) cells which fail to respond to nerve growth factor (NGF) (PC12nnr5) (Green, S. H., R. E. Rydel, J. L. Connoly, and L. A. Greene. 1986. J. Cell Biol. 102:830-843) bind NGF at both high and low affinity sites. Although still undefined at the molecular level, these have been referred to as type I (high) and type II (low) receptors. They are apparently composed of two membrane-bound proteins, p75 and the protooncogene trk, both of which bind NGF, and apparently...

1992-01-01

179

Up-Regulation of Pain Behavior and Glial Activity in the Spinal Cord after Compression and Application of Nucleus Pulposus onto the Sciatic Nerve in Rats  

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Study Design Experimental animal study. Purpose To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. Overview of Literature Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission. Methods The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively. Results Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05). Conclusions Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission. PMID:25346806

Norimoto, Masaki; Sakuma, Yoshihiro; Suzuki, Miyako; Orita, Sumihisa; Yamauchi, Kazuyo; Inoue, Gen; Aoki, Yasuchika; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Kamoda, Hiroto; Kubota, Gou; Oikawa, Yasuhiro; Inage, Kazuhide; Sainoh, Takeshi; Sato, Jun; Nakamura, Junichi; Toyone, Tomoaki; Takahashi, Kazuhisa

2014-01-01

180

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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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

 
 
 
 
181

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.)

182

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

183

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

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Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adenosine 5?-triphosphate (ATP) release from peripheral neurons and Schwann cells during Wallerian degeneration. Exocytosis is involved in demyelination and axonal degradation, which facilitate nerve regeneration following nerve degeneration. At this time, released ATP may affect the communication between cells in peripheral nerves. In this review, our description of the relationship between lysosomal exocytosis and Wallerian degeneration has implications for the understanding of peripheral nerve degenerative diseases and peripheral neuropathies, such as Charcot-Marie-Tooth disease or Guillain-Barré syndrome. PMID:25101301

Jung, Junyang; Kwon, Hyunseob

2014-01-01

184

ATP release through lysosomal exocytosis from peripheral nerves: the effect of lysosomal exocytosis on peripheral nerve degeneration and regeneration after nerve injury.  

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Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adenosine 5'-triphosphate (ATP) release from peripheral neurons and Schwann cells during Wallerian degeneration. Exocytosis is involved in demyelination and axonal degradation, which facilitate nerve regeneration following nerve degeneration. At this time, released ATP may affect the communication between cells in peripheral nerves. In this review, our description of the relationship between lysosomal exocytosis and Wallerian degeneration has implications for the understanding of peripheral nerve degenerative diseases and peripheral neuropathies, such as Charcot-Marie-Tooth disease or Guillain-Barré syndrome. PMID:25101301

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

2014-01-01

185

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

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

Yan Zhang

2014-10-01

186

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 ([Ca2+]i) after repeated exposure to heroin using cultured cerebral cortical neurons. Dynamic changes in [Ca2+]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 [Ca2+]i responses, and a higher elevation in [Ca2+]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 [Ca2+]i elevations as well as the heroin-induced cell damage. The relative [Ca2+]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 [Ca2+]i homeostasis, as well as vulnerability to heroin overdose, suggesting involvement of [Ca2+]i regulation mechanisms in heroin addiction and neurotoxicity. PMID:24854119

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

2014-07-14

187

An attempt to assess functionally minimal acetylcholinesterase activity necessary for survival of rats intoxicated with nerve agents.  

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Acetylcholinesterase (AChE, EC 3.1.1.7) is an important enzyme for cholinergic nerve transmission. The action of toxic organophosphates such as nerve agents is based on AChE inhibition. The death following acute nerve agent poisoning is due to central or peripheral respiratory/cardiac failure. Therefore, the changes in AChE activity following nerve agents acting predominantly on the central (sarin, soman) or peripheral (VX) level were studied. It is known that AChE activity in different structures exists in relative excess. Female Wistar rats intoxicated with sarin, soman, and VX in different doses (0.5-2.0 x LD(50)) were divided into groups of survived and died animals. AChE activities in diaphragm, brain parts (pontomedullar area, frontal cortex, basal ganglia, in some cases other parts of the brain) were determined and the rest of activity (in %) was correlated with survival/death of animals. More precise elucidation of action of nerve agents and the assessment of minimal AChE activity in different organs compatible with the survival of organism poisoned with nerve agents were the aims of this study. PMID:18579126

Bajgar, Jiri; Fusek, Josef; Kassa, Jiri; Jun, Daniel; Kuca, Kamil; Hajek, Petr

2008-09-25

188

Laryngeal Nerve Activity During Pulse Emission in the CF-FM Bat, Rhinolophus ferrumequinum. I. Superior Laryngeal Nerve (External Motor Branch)  

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The activity of the external (motor) branch of the superior laryngeal nerve (SLN), innervating the cricothyroid muscle, was recorded in the greater horseshoe bat,Rhinolophus ferrumequinum. The bats were induced to change the frequency of the constant frequency (CF) component of their echolocation signals by presenting artificial signals for which they Doppler shift compensated. The data show that the SLN discharge rate and the frequency of the emitted CF are correlated in a linear manner.

Schuller, Gerd; Ru?bsamen, R.

1981-01-01

189

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

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

Wynick David

2011-04-01

190

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

191

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

192

The influence of surface nanoroughness of electrospun PLGA nanofibrous scaffold on nerve cell adhesion and proliferation.  

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Electrospun nanofibrous scaffolds in neural tissue engineering provide an alternative approach for neural regeneration. Since the topography of a surface affects the microscopic behaviour of material; the creation of nanoscale surface features, which mimic the natural roughness of live tissue, on polymer surfaces can promote an appropriate cell growth and proliferation. In this research, a unique PLGA nanofibrous structure was fabricated without any post-electrospinning treatment. Scaffolds were prepared in two general groups: cylindrical and ribbon-shaped electrospun fibres, with smooth and rough (porous and grooved) surfaces. The experiments about nerve cell culture have demonstrated that the nanoroughness of PLGA electrospun scaffolds can increase the cell growing rate to 50 % in comparison with smooth and conventional electrospun scaffolds. SEM and AFM images and MTT assay results have shown that the roughened cylindrical scaffolds enhance the nerve growth and proliferation compared to smooth and ribbon-shaped nanofibrous scaffolds. A linear interaction has been found between cell proliferation and surface features. This helps to approximate MTT assay results by roughness parameters. PMID:23494618

Zamani, Fatemeh; Amani-Tehran, Mohammad; Latifi, Masoud; Shokrgozar, Mohammad Ali

2013-06-01

193

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. PMID:24824755

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

2014-01-01

194

Selective bilateral activation of leg muscles after cutaneous nerve stimulation during backward walking.  

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During human locomotion, cutaneous reflexes have been suggested to function to preserve balance. Specifically, cutaneous reflexes in the contralateral leg's muscles (with respect to the stimulus) were suggested to play an important role in maintaining stability during locomotor tasks where stability is threatened. We used backward walking (BW) as a paradigm to induce unstable gait and analyzed the cutaneous reflex activity in both ipsilateral and contralateral lower limb muscles after stimulation of the sural nerve at different phases of the gait cycle. In BW, the tibialis anterior (TA) reflex activity in the contralateral leg was markedly higher than TA background EMG activity during its stance phase. In addition, in BW a substantial reflex suppression was observed in the ipsilateral biceps femoris during the stance-swing transition in some participants, while for medial gastrocnemius the reflex activity was equal to background activity in both legs. To test whether the pronounced crossed responses in TA could be related to instability, the responses were correlated with measures of stability (short-term maximum Lyapunov exponents and step width). These measures were higher for BW compared with forward walking, indicating that BW is less stable. However, there was no significant correlation between these measures and the amplitude of the crossed TA responses in BW. It is therefore proposed that these crossed responses are related to an attempt to briefly slow down (TA decelerates the center of mass in the single-stance period) in the light of unexpected perturbations, such as provided by the sural nerve stimulation. PMID:22773779

Hoogkamer, Wouter; Massaad, Firas; Jansen, Karen; Bruijn, Sjoerd M; Duysens, Jacques

2012-10-01

195

Effects of umbilical cord tissue mesenchymal stem cells (UCX®) on rat sciatic nerve regeneration after neurotmesis injuries.  

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Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX(®)), was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal(®), was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT), withdrawal reflex latency (WRL), ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX(®) alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX(®) induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC). At opposite toe off (OT) and heel rise (HR), differences were found between untreated animals and the groups treated with either uCx(®) alone or UCX(®) administered with Floseal(®). Overall, the UCX(®) application presented positive effects in functional and morphologic recovery, in both the acute and chronic phases of the regeneration process. Kinematics analysis has revealed positive synergistic effects brought by Floseal(®) as vehicle for MSCs. PMID:25075157

Gärtner, A; Pereira, T; Armada-da-Silva, Pas; Amado, S; Veloso, Ap; Amorim, I; Ribeiro, J; Santos, Jd; Bárcia, Rn; Cruz, P; Cruz, H; Luís, Al; Santos, Jm; Geuna, S; Maurício, Ac

2014-01-01

196

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

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

Brambilla Roberta

2012-09-01

197

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

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

Wynn, Gregory; Burnstock, Geoffrey

2006-01-01

198

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

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Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. Scanning electron microscopy of the collagen tubes demonstrated their ability to be resorbed in vivo. We observed notable overexpression of the CDNF protein in the distal sciatic nerve after application of CDNF-MSCs. Quantitative analysis of neurofilament 200 (NF200) and S100 immunohistochemistry showed significant enhancement of axonal and Schwann cell regeneration in the group receiving CDNF-MSCs (CDNF-MSCs group) compared with the control groups. Myelination thickness, axon diameter and the axon-to fiber diameter ratio (G-ratio) were significantly higher in the CDNF-MSCs group at 8 and 12 weeks after nerve transection surgery. After surgery, the sciatic functional index, target muscle weight, wet weight ratio of gastrocnemius muscle and horseradish peroxidase (HRP) tracing demonstrated functional recovery. Light and electron microscopy confirmed successful regeneration of the sciatic nerve. The greater numbers of HRP-labeled neuron cell bodies and increased sciatic nerve index values (SFI) in the CDNF-MSCs group suggest that CDNF exerts neuroprotective effects in vivo. We also observed higher target muscle weights and a significant improvement in muscle atrophism in the CDNF-MSCs group. Collectively, these findings indicate that CDNF gene therapy delivered by MSCs is capable of promoting nerve regeneration and functional recovery, likely because of the significant neuroprotective and neurotrophic effects of CDNF and the superior environment offered by MSCs and collagen tubes. PMID:25343619

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

2014-01-01

199

Differential and synergistic actions of nerve growth factor and cyclic AMP in PC12 cells  

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When a clonal line of rat pheochromocytoma (PC12) was exposed to beta- nerve growth factor (beta NGF), N6, O2-dibutyryl adenosine 3':5' cyclic monophosphate (Bt2cAMP), or a combination of the two, 10, 26, or 70% of the cell clumps, respectively, displayed neurites after 1.d. Increases in the cellular RNA concentration were also found to be additive or greater when both agents were present. Neurites induced by Bt2cAMP alone were not maintained after replacement with beta NGF. The degree of pot...

1981-01-01

200

Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve.  

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We have previously reported that in dissociated cultures of neonatal rat sciatic nerve, all of the cells could be identified by indirect immunofluorescence with two antisera to cell surface antigens. The Schwann cells, but not the fibroblasts, expressed the Ran-1 antigen, while the fibroblasts, but not the Schwann cells, expressed the Thy-1 antigen. We have exploited this difference to derive pure populations of Schwann cells. A combination of [3H]thymidine autoradiography and immunofluorescence marking showed that in Modified Eagle's Medium with 10% foetal calf serum, the Schwann cells divided slowly while the fibroblasts divided rapidly. Accordingly, two day old cultures were exposed to cytosine arabinoside to select against the fibroblasts, followed by growth in medium containing an extract of bovine pituitary which stimulated division of the Schwann cells. After 7 days the confluent cultures, which contained 80-90% Schwann cells, were passaged after treatment in suspension with antiserum to Thy-1 and rabbit complement. After continued growth in medium with pituitary extract, the secondary cultures contained greater than 99.5% Schwann cells. These purified populations have been maintained in culture for as long as 150 days (6 passages) and retained the Ran-1 marker. The cultured Schwann cells expressed the S100 antigen, as shown by indirect immunofluorescence and complement fixation, and receptors for cholera toxin. They did not express the large external transformation sensitive protein, the glial fibrillary acidic protein, or receptors for tetanus toxin. PMID:371755

Brockes, J P; Fields, K L; Raff, M C

1979-04-01

 
 
 
 
201

Evidence for a intimate relationship between mast cells and nerve fibers in the tongue of the frog, Rana esculenta  

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Morphological and ultrastructural association of mast cells and nerve fibers were studied in the tongue of the frog Rana esculenta. The number of mast cells in the tongue (253 {+-} 45 / mm{sup 2}) is far the highest of the frog tissue as far as people know. They are distributed throughout the connective tissue among the muscular fibers, near arterioles and venules but predominantly in close association and within the nerves. They are often embedded in the endoneurium within a nerve bundle near to myelinic or unmyelinic fibers and in membrane-to-membrane contact with axonlike processes. Just for the richness of mast cells, the tongue of the frog could represent an useful model to study the relationship between these cells and the peripheral nervous system.

Chieffi Baccari, Gabriella; Minucci, Sergio [Naples, II Univ. (Italy). Dipt. di Fisiologia Umana e Funzioni Biologiche Integrate `Filippo Bottazzi`

1997-12-31

202

Regulation of sympathetic nerve activity by L-carnosine in mammalian white adipose tissue.  

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Previously, we showed that l-carnosine, a bioactive dipeptide, influences the sympathetic nerve activity innervating kidney and brown adipose tissue. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of L-carnosine on the sympathetic nerve activity innervating white adipose tissue (SNA-WAT) and lipolysis. We found that intraperitoneal (ip) administration of L-carnosine at doses of 100 ng/rat and 10 microg/rat elevated and suppressed SNA-WAT, respectively. The effect of lower dose of L-carnosine (100 ng/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of higher dose of L-carnosine (10 microg/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, ip administration of 100 ng and 10 microg of L-carnosine increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The changes of plasma FFAs resulting from the exposure to 100 ng and 10 microg of L-carnosine were diminished by the beta-adrenergic receptor blocker propranolol hydrochloride and the muscarinic receptor blocker atropine sulfate, respectively; and eliminated by the corresponding histamine receptor antagonists, which eliminated the changes in SNA-WAT. Our results suggest that low doses of L-carnosine 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. High doses of L-carnosine, 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:18599216

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

2008-08-15

203

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

204

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

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

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

1988-09-01

205

Division of labor of Schwann cell integrins during migration on peripheral nerve extracellular matrix ligands.  

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Myelination of the peripheral nervous system (PNS) requires the migration of Schwann cells during both development and regeneration. We have characterized the expression pattern of Schwann cell integrins and analyzed their role in migration on different ECM substrates known to be present within the PNS. We found that Schwann cells in cell culture express four beta1 integrins, alpha1 beta1, alpha2 beta1, alpha6 beta1, and another unidentified beta1 integrin, as well as two alpha v integrins, alpha v beta3 and alpha v beta8. Using the Varani migration assay, we found that laminin-1, laminin-2 (merosin), and fibronectin increased Schwann cell migration, while vitronectin and collagen did not increase migration compared to an uncoated plastic substrate. Schwann cell migration on laminin-1 and laminin-2 (merosin) was blocked by antibodies against beta1 integrins, but not affected by RGD peptides or antibodies against beta3 integrins. In contrast, migration on fibronectin was unaffected by antibodies against beta1 and beta3 integrins but was blocked by RGD peptides. This in vitro study shows that there is a division of labor of Schwann cell integrins in the regulation of migration on peripheral nerve ECM components; beta1 integrins mediate migration on laminin-1 and laminin-2 (merosin), while alpha v integrins mediate migration on fibronectin. Taken together, these results suggest that multiple interactions between Schwann cell integrins and ECM within the PNS will contribute to Schwann cell migration during myelination of the PNS. PMID:9187084

Milner, R; Wilby, M; Nishimura, S; Boylen, K; Edwards, G; Fawcett, J; Streuli, C; Pytela, R; ffrench-Constant, C

1997-05-15

206

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

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

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

2008-05-01

207

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

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

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

2014-01-01

208

Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury.  

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Fibroblast growth factor 2 (FGF-2) is a trophic factor expressed by glial cells and different neuronal populations. Addition of FGF-2 to spinal cord and dorsal root ganglia (DRG) explants demonstrated that FGF-2 specifically increases motor neuron axonal growth. To further explore the potential capability of FGF-2 to promote axon regeneration, we produced a lentiviral vector (LV) to overexpress FGF-2 (LV-FGF2) in the injured rat peripheral nerve. Cultured Schwann cells transduced with FGF-2 and added to collagen matrix embedding spinal cord or DRG explants significantly increased motor but not sensory neurite outgrowth. LV-FGF2 was as effective as direct addition of the trophic factor to promote motor axon growth in vitro. Direct injection of LV-FGF2 into the rat sciatic nerve resulted in increased expression of FGF-2, which was localized in the basal lamina of Schwann cells. To investigate the in vivo effect of FGF-2 overexpression on axonal regeneration after nerve injury, Schwann cells transduced with LV-FGF2 were grafted in a silicone tube used to repair the resected rat sciatic nerve. Electrophysiological tests conducted for up to 2 months after injury revealed accelerated and more marked reinnervation of hindlimb muscles in the animals treated with LV-FGF2, with an increase in the number of motor and sensory neurons that reached the distal tibial nerve at the end of follow-up. PMID:24989458

Allodi, Ilary; Mecollari, Vasil; González-Pérez, Francisco; Eggers, Ruben; Hoyng, Stefan; Verhaagen, Joost; Navarro, Xavier; Udina, Esther

2014-10-01

209

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

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The development of biomaterials for regenerating neurons from induced pluripotent stem (iPS) cells is crucial to the potential therapy for traumatic injury to nervous system. This study aims to guide differentiation of iPS cells into neuron-lineage cells in inverted colloidal crystal (ICC) scaffolds containing alginate, poly(?-glutamic acid), and surface CSRARKQAASIKVAVSADR (peptide). The differentiation of iPS cells in ICC constructs was characterized by staining of embryonic and neuronal markers. The results indicated that hexagonal crystals of polystyrene microspheres shaped hydrogels into ICC scaffolds with interconnected pores. CSRARKQAASIKVAVSADR slightly enhanced the adhesion of iPS cells in ICC constructs and yielded no variation in the viability of iPS cells. Cultured ICC constructs with CSRARKQAASIKVAVSADR reduced the expression of stage-specific embryonic surface antigen-1 and raised the expression of ? III tubulin of differentiating iPS cells. The induction with CSRARKQAASIKVAVSADR in ICC topography can improve the differentiation of iPS cells toward neurons for nerve tissue engineering. PMID:23107957

Kuo, Yung-Chih; Chen, Chun-Wei

2013-02-01

210

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

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

Raven Mary A

2008-07-01

211

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

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

Azita Parvaneh Tafreshi

2006-08-01

212

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

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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

213

Decreased glutathione peroxidase activity in sciatic nerve of alloxan-induced diabetic mice and its correlation with blood glucose levels.  

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The effect of alloxan-induced diabetes on glutathione peroxidase (GSH-Px) activity in sciatic nerve of mice has been studied. We have found, 7 days after alloxan treatment, a significant decrease in this enzymatic activity in the cytosol of sciatic nerve of diabetic mice, and moreover, that these changes remained unaltered up to 21 days after alloxan injection. No modification in the glutathione content of sciatic nerve of diabetic mice was observed throughout the experiment when compared with controls. The decrease in GSH-Px activity in this tissue shows a good correlation with the increase of blood glucose levels throughout the experiment. It is hypothesized whether a combination of mechanisms could be involved in this decrease of GSH-Px activity and if oxygen radicals might be the common mediators of these processes. PMID:8396737

Hermenegildo, C; Raya, A; Romá, J; Romero, F J

1993-08-01

214

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

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

Janssen Katherine T

2006-10-01

215

Neonatal Olfactory Bulb Ensheathing Cell Line (NOBEC) in view of a suitable employment in experimental nerve tissue repair  

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Olfactory Ensheathing Cells (OECs) are special types of glial cells showing an exceptional plasticity, and support olfactory neurogenesis. They secrete growth factors and adhesion molecules, inhibit inflammatory reaction and promote neurite regeneration. Because of these features, OECs transplantation is supposed to be one of the most promising methods for nerve injuries. Here, we characterized the NOBEC (Neonatal Olfactory Bulb Ensheathing Cells) line obtained from primary cells dissociated ...

Perroteau, Isabelle; Geuna, Stefano; Raimondo, Stefania; Audisio, Chiara; Gambarotta, Giovanna

2010-01-01

216

Sacral Neural Crest-Derived Cells Enter the Aganglionic Colon of Ednrb?/? Mice Along Extrinsic Nerve Fibers  

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Both vagal and sacral neural crest cells contribute to the enteric nervous system in the hindgut. Because it is difficult to visualize sacral crest cells independently of vagal crest, the nature and extent of the sacral crest contribution to the enteric nervous system are not well established in rodents. To overcome this problem we generated mice in which only the fluorescent protein-labeled sacral crest are present in the terminal colon. We found that sacral crest cells were associated with extrinsic nerve fibers. We investigated the source, time of appearance, and characteristics of the extrinsic nerve fibers found in the aganglionic colon. We observed that the pelvic ganglion neurons contributed a number of extrinsic fibers that travel within the hindgut between circular and longitudinal muscles and within the submucosa and serosa. Sacral crest-derived cells along these fibers diminished in number from fetal to post-natal stages. A small number of sacral crest-derived cells were found between the muscle layers and expressed the neuronal marker Hu. We conclude that sacral crest cells enter the hindgut by advancing on extrinsic fibers and, in aganglionic preparations, they form a small number of neurons at sites normally occupied by myenteric ganglia. We also examined the colons of ganglionated preparations and found sacral crest-derived cells associated with both extrinsic nerve fibers and nascent ganglia. Extrinsic nerve fibers serve as a route of entry for both rodent and avian sacral crest into the hindgut. PMID:21858821

Erickson, Christopher S.; Zaitoun, Ismail; Haberman, Kathryn M.; Gosain, Ankush; Druckenbrod, Noah R.; Epstein, Miles L.

2012-01-01

217

Sacral neural crest-derived cells enter the aganglionic colon of Ednrb-/- mice along extrinsic nerve fibers.  

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Both vagal and sacral neural crest cells contribute to the enteric nervous system in the hindgut. Because it is difficult to visualize sacral crest cells independently of vagal crest, the nature and extent of the sacral crest contribution to the enteric nervous system are not well established in rodents. To overcome this problem we generated mice in which only the fluorescent protein-labeled sacral crest are present in the terminal colon. We found that sacral crest cells were associated with extrinsic nerve fibers. We investigated the source, time of appearance, and characteristics of the extrinsic nerve fibers found in the aganglionic colon. We observed that the pelvic ganglion neurons contributed a number of extrinsic fibers that travel within the hindgut between circular and longitudinal muscles and within the submucosa and serosa. Sacral crest-derived cells along these fibers diminished in number from fetal to postnatal stages. A small number of sacral crest-derived cells were found between the muscle layers and expressed the neuronal marker Hu. We conclude that sacral crest cells enter the hindgut by advancing on extrinsic fibers and, in aganglionic preparations, they form a small number of neurons at sites normally occupied by myenteric ganglia. We also examined the colons of ganglionated preparations and found sacral crest-derived cells associated with both extrinsic nerve fibers and nascent ganglia. Extrinsic nerve fibers serve as a route of entry for both rodent and avian sacral crest into the hindgut. PMID:21858821

Erickson, Christopher S; Zaitoun, Ismail; Haberman, Kathryn M; Gosain, Ankush; Druckenbrod, Noah R; Epstein, Miles L

2012-02-15

218

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

219

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

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The sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a critical pathway by which sensory neurons sequester cytosolic Ca(2+) and thereby maintain intracellular Ca(2+) homeostasis. We have previously demonstrated decreased intraluminal endoplasmic reticulum Ca(2+) concentration in traumatized sensory neurons. Here we examine SERCA function in dissociated sensory neurons using Fura-2 fluorometry. Blocking SERCA with thapsigargin (1 ?M) increased resting [Ca(2+)](c) and prolonged recovery (?) from transients induced by neuronal activation (elevated bath K(+)), demonstrating SERCA contributes to control of resting [Ca(2+)](c) and recovery from transient [Ca(2+)](c) elevation. To evaluate SERCA in isolation, plasma membrane Ca(2+) ATPase was blocked with pH 8.8 bath solution and mitochondrial buffering was avoided by keeping transients small (? 400 nM). Neurons axotomized by spinal nerve ligation (SNL) showed a slowed rate of transient recovery compared to control neurons, representing diminished SERCA function, whereas neighboring non-axotomized neurons from SNL animals were unaffected. Injury did not affect SERCA function in large neurons. Repeated depolarization prolonged transient recovery, showing that neuronal activation inhibits SERCA function. These findings suggest that injury-induced loss of SERCA function in small sensory neurons may contribute to the generation of pain following peripheral nerve injury. PMID:23219911

Duncan, C; Mueller, S; Simon, E; Renger, J J; Uebele, V N; Hogan, Q H; Wu, H-E

2013-02-12

220

The origin of the anticholinesterase-induced repetitive activity of the phrenic nerve-diaphragm preparation of the rat in vitro.  

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1. Action potentials have been recorded in contracting muscle cells of the phrenic nerve-diaphragm preparation from rats. After the organophosphorous anticholinesterase, ecothiopate, some cells fired repetitive action potentials. In 0.1 mM [Mg2+]o the repetitive activity was generated presynaptically or postsynaptically, and in 1 mM [Mg2+]o, probably only postsynaptically. 2. The repetitive action potentials in muscle were generated ectopically about 0.2 mm away from the usual site. 3. In 1 m...

Ferry, C. B.

1988-01-01

 
 
 
 
221

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

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

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

2013-04-01

222

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

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

223

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 dissociated from sympathetic factors.

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

2000-01-01

224

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

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

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

2000-01-01

225

Reduced Na+/K+ adenosine triphosphatase activity and motor nerve conduction velocity in L-fucose-fed rats is reversible after dietary normalization.  

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Development of early defects in diabetic neuropathy has been linked to metabolic abnormalities and is considered reversible. To further address some of the questions concerning the contribution by metabolic derangements to the development of neural defects and reversibility, we have developed an animal model, by feeding rats a diet containing 20% L-fucose, that develops neural defects similar to those that occur in streptozotocin-induced diabetic rats. After 6 weeks on a 20% L-fucose diet, myo-inositol content and Na+/K+ adenosine triphosphatase (ATPase) activity of the sciatic nerve were significantly reduced, as was the motor nerve conduction velocity (MNCV). L-Fucose is a monosaccharide that occurs in low concentrations in normal serum but is increased in diabetic patients. In cultured cells, L-fucose, at concentrations that occur in diabetic circulation, is a competitive inhibitor of myo-inositol uptake. The purpose of the present study was to compare the sequential pattern of the reversibility of the slowing of MNCV with ouabain-inhibited sciatic nerve Na+/K+ ATPase activity and myo-inositol content in rats fed a diet containing 20% L-fucose for a period of 6 weeks followed by a normal diet lasting up to 2 weeks. Unbound L-fucose levels in the serum returned to normal in less than 24 hours of the rats being placed on the normal diet. Normalization of slowed MNCV after removing L-fucose-fed rats from the L-fucose diet followed a pattern of recovery similar to the recovery of sciatic nerve ouabain-inhibited Na+/K+ ATPase activity, with complete recovery occurring within 7 days of the rats being placed on the normal diet. In contrast, myo-inositol content of the sciatic nerve remained decreased following 3 days on the normal diet, and required 14 days for complete normalization. Results from these studies suggest that a causal relationship may exist for reduced Na+/K+ ATPase activity and MNCV in L-fucose-fed rats, and that a measurable decrease in myo-inositol content may not be necessary for the development of these defects in the sciatic nerve. PMID:8596495

Yorek, M A; Wiese, T J; Davidson, E P; Dunlap, J A; Conner, C E

1996-02-01

226

Simian adenovirus type 7 (SA-7) induces tumours of nerve-supporting or paraneural cell origin in newborn hamsters.  

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Simian adenovirus type 7 (SA-7) was found to induce tumours originating from nerve-supporting or paraneural cells in newborn hamsters, regardless of injection site or tissues. SA-7 induces glioblastomas characterized by definite localization (subependymal regions) and its main cell type, bipolar spongioblast-like cells, in the brain of hamsters inoculated as newborns. When the eyes of newborn hamsters were directly inoculated, SA-7 failed to induce retinoblastoma (0/27), but retro or peri-bul...

Ohtaki, S.; Kato, K.

1989-01-01

227

BioPEGylation of polyhydroxybutyrate promotes nerve cell health and migration.  

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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

228

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

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

229

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

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

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

1990-01-01

230

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

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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

231

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

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Histological investigations were carried out on the sympathetic trunks of fourteen healthy, mature male and female coypu specimens of standard race, aged 8-24 months. The histological preparations impregnated using Bielschowski and Gross's method were prepared from front cervical, mid-cervical (central cervical), and pectoral-cervical ganglia as well as from pectoral, lumbar and sacral ganglia. An entire range of nerve cells displaying a certain type and degree of change was found in the above mentioned sympathetic ganglia. These cells are classified in the following order: cells with protoplasmic argyrophilia, cells with vacuole formations, with hyperplasia or hypertrophia of the processes, neuronophagic cells and degenerating cells. PMID:7301627

Langenfeld, M

1981-01-01

232

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans  

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To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

Cui, J.; Wilson, T. E.; Shibasaki, M.; Hodges, N. A.; Crandall, C. G.

2001-01-01

233

FGF21 Acts Centrally to Induce Sympathetic Nerve Activity, Energy Expenditure, and Weight Loss.  

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The mechanism by which pharmacologic administration of the hormone FGF21 increases energy expenditure to cause weight loss in obese animals is unknown. Here we report that FGF21 acts centrally to exert its effects on energy expenditure and body weight in obese mice. Using tissue-specific knockout mice, we show that ?Klotho, the obligate coreceptor for FGF21, is required in the nervous system for these effects. FGF21 stimulates sympathetic nerve activity to brown adipose tissue through a mechanism that depends on the neuropeptide corticotropin-releasing factor. Our findings provide an unexpected mechanistic explanation for the strong pharmacologic effects of FGF21 on energy expenditure and weight loss in obese animals. PMID:25130400

Owen, Bryn M; Ding, Xunshan; Morgan, Donald A; Coate, Katie Colbert; Bookout, Angie L; Rahmouni, Kamal; Kliewer, Steven A; Mangelsdorf, David J

2014-10-01

234

Edaravone promotes functional recovery after mechanical peripheral nerve injury.  

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

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

2014-09-15

235

Neurovascular decompression of the rostral ventrolateral medulla decreases blood pressure and sympathetic nerve activity in patients with refractory hypertension.  

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Recently, the authors experienced four patients who had refractory hypertension and neurovascular compression of the rostral ventrolateral medulla (RVLM). One of them, a 49-year-old woman, had undergone continuous intravenous drip injections of calcium channel blockers and ?-blockers for more than 3 years because of severe and refractory hypertension. The patients had undergone microvascular decompression (MVD) of the RVLM, and the changes in blood pressure (BP) and sympathetic nerve activities were recorded. In these patients, BP decreased to the normal range without any antihypertensive drugs 2 to 3 months after MVD. The tibial sympathetic nerve activities under resting and stress conditions significantly decreased, and plasma levels of norepinephrine, urinary levels of adrenaline, and plasma renin activity were also significantly decreased after MVD of RVLM. In some patients with refractory hypertension, arterial compression of the RVLM enhances sympathetic nerve activity and renin-angiotensin system to thereby increase BP. In these patients, the operative decompression of the RVLM could lower BP via restoration of sympathetic nerve activities and the renin-angiotensin system. PMID:22051426

Sasaki, Susumu; Tanda, Shuji; Hatta, Tsuguru; Morimoto, Satoshi; Takeda, Kazuo; Kizu, Osamu; Tamaki, Shinji; Saito, Mitsuru; Tamura, Yoji; Kondo, Akinori

2011-11-01

236

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

237

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.

2014-07-01

238

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

239

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.

240

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

Science.gov (United States)

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. PMID:25003632

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

2014-07-01

 
 
 
 
241

Ultrastructural morphometric study of efferent nerve terminals on murine bone marrow stromal cells, and the recognition of a novel anatomical unit: the "neuro-reticular complex".  

Science.gov (United States)

In order to extend our understanding of the role of nerve fibers in the structure and function of bone marrow stroma, we have examined nerve terminals, arterioles, and capillaries in femoral bone marrow tissues of 50 C57BL strain mice, using electron microscopy and morphometric methods. Within the adventitia of arterioles, a particular type of cell, termed periarterial adventitial (PAA) cell, is characterized by a thin veil-like cytoplasm which concentrically surrounds both nerves and arterioles. Nerve fibers containing both unmyelinated and myelinated axons are distributed mainly between the layers of PAA cells, but are found rarely on the sinus walls or within the hematopoietic parenchyma. Quantitatively, the efferent nerve terminals with many synaptic vesicles are distributed mainly beside arterial smooth muscle cells (Type I: 58.8%) or between the layers of PAA cells (Type III: 33.2%), and rarely in hematopoietic parenchyma (Type II: 5.3%) or on sinus walls (Type IV: 2.7%). In the case of Type II-IV nerve terminals, efferent (autonomic) nerves and bone marrow stromal cells which are connected by gap junctions (sinus adventitial reticular cells, intersinusoidal reticular cells, and PAA cells) appear to constitute a potential functional unit for signal conduction. We would like to propose a new term for this anatomical unit in marrow, the "neuro-reticular complex." PMID:2321559

Yamazaki, K; Allen, T D

1990-03-01

242

Nerve biopsy  

Science.gov (United States)

Biopsy - nerve ... A nerve biopsy is most often done on a nerve in the ankle, forearm, or along a rib. The health care ... feel a prick and a mild sting. The biopsy site will be sore for a few days ...

243

Aligned SF/P(LLA-CL)-blended nanofibers encapsulating nerve growth factor for peripheral nerve regeneration.  

Science.gov (United States)

Artificial nerve guidance conduits (NGCs) containing bioactive neurotrophic factors and topographical structure to biomimic native tissues are essential for efficient regeneration of nerve gaps. In this study, aligned SF/P(LLA-CL) nanofibers encapsulating nerve growth factor (NGF), which was stabilized by SF in core, were fabricated via a coaxial electrospinning technique. The controlled release of NGF from the nanofibers was evaluated using enzyme-linked immune sorbent assay (ELISA) and PC12 cell-based bioassay over a 60-day time period. The results demonstrated that NGF presented a sustained release and remained biological activity over 60 days. Nerve guidance conduits (NGCs) were fabricated by reeling the aligned SF/P(LLA-CL) nanofibrous scaffolds encapsulating NGF and then used as a bridge implanted across a 15-mm defect in the sciatic nerve of rats to promote nerve regeneration. The outcome in terms of regenerated nerve at 12 weeks was evaluated by a combination of electrophysiological assessment, histochemistry, and electron microscopy. All results clarified that the NGF-encapsulated-aligned SF/P(LLA-CL) NGCs promoted peripheral nerve regeneration significantly better than the aligned SF/P(LLA-CL) NGCs, suggesting that the released NGF from nanofibers could effectively promote the regeneration of peripheral nerve. PMID:23963979

Kuihua, Zhang; Chunyang, Wang; Cunyi, Fan; Xiumei, Mo

2014-08-01

244

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

International Nuclear Information System (INIS)

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

245

Studies on the effects of gamma-irradiation on the histochemistry of mammalian nerve cells  

International Nuclear Information System (INIS)

The effects of gamma-irradiation on the histochemical and cellular constituents of the cerebellar and spinal cord nerve cells have been studied in order to elucidate the harmful effects of radiation on man and his environment to take the necessary precautions against it. Fragmentation, dissolution and almost disappearance of nissl bodies or tigrolysis in general had occurred after exposure to the high dose level of gamma-irradiation in the cerebellar and spinal cord neurons. Disturbance in RNA inclusions of cells has also been observed following gamma-irradiation. As it was noticed in case of nissl bodies, the effects on the RNA containing particles were more drastic in the neurons of cerebellum than those of the spinal cord. Worthy of mentioning is that same cells, especially that of the spinal cord, were not always affected in the same way. It was noticed that tigrolysis and inhibition of RNA which had occurred after treatment with a low dose of gamma-irradiation (4 and 6 Gy) were recovered within few days. This was in contrast with the high dose level of 10 Gy, in which case no recovery was attained. 28 fig

246

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

Directory of Open Access Journals (Sweden)

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

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

2010-03-01

247

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

Science.gov (United States)

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

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

1982-02-01

248

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

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

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

2014-08-01

249

Blockade of 5-HT(1A) receptors in the phrenic nucleus of the rat attenuated raphe induced activation of the phrenic nerve activity.  

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Stimulation of the raphe pallidus nucleus produces facilitatory effects on respiratory activity. Numerous serotonergic projections from the raphe pallidus have been shown to terminate in the phrenic nucleus. This study was undertaken to examine the role of 5-hydroxytryptamine 1A (5-HT(1A)) receptors in the phrenic nucleus on the excitatory response of the phrenic nerve activity elicited from the raphe pallidus. We hypothesized that blockade of 5-HT(1A) receptors in the phrenic nucleus will attenuate raphe-induced facilitation of the phrenic nerve. Chemical stimulation of the raphe pallidus by synaptic excitant D,L-homocysteic acid produced increase in the amplitude of the phrenic nerve activity. After microinjection of the specific 5-HT(1A) receptor antagonist WAY, N-(2-(4,2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl-cyclohexane-carboxamide maleate into the phrenic nucleus, the raphe-induced facilitation of the phrenic nerve was attenuated. These data suggest that excitation of the phrenic nerve activity elicited by activation of the neurons in the raphe pallidus is mediated by 5-HT(1A) receptors in the phrenic nucleus. PMID:19826196

Pecotic, R; Dogas, Z; Valic, Z; Valic, M

2009-09-01

250

Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by a Coptidis Rhizoma extract and protoberberine alkaloids.  

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A methanol extract of Coptidis Rhizoma effectively enhanced the outgrowth of neurite in PC12 cells induced by nerve growth factor (NGF). Following solvent partition and preparative HPLC, berberine was isolated as the major active compound. Berberine enhanced the proportion of neurite-bearing cells in a dose-dependent manner without cytotoxicity. Its structural relatives, palmatine and coptisine, showed a slightly weaker NGF-enhancing effect than berberine. These three alkaloids inhibited acetylcholinesterase activity at a level comparable to that of physostigmine, but this inhibition was not responsible for the potentiation of NGF-induced neurite outgrowth. It is demonstrated for the first time that protoberberine alkaloids potentiated the NGF-induced differentiation of neural cells. PMID:12506995

Shigeta, Koji; Ootaki, Keisuke; Tatemoto, Hideki; Nakanishi, Tsutomu; Inada, Akira; Muto, Norio

2002-11-01

251

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

Science.gov (United States)

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

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

2009-06-03

252

Study on the effect of electromagnetic impulse on neurotransmitter metabolism in nerve cells by high-performance liquid chromatography-electrochemical detection coupled with microdialysis.  

Science.gov (United States)

In this paper, a reverse-phase high-performance liquid chromatographic method using a chemically modified electrode coupled with microdialysis was developed to study the effect of electromagnetic impulse (EMI) on monoamine neurotransmitter metabolism in nerve cells. To detect the monoamines and their metabolites, a poly (para-aminobenzoic acid) (P-pABA)-modified electrode was prepared. The modified electrode exhibited efficiently electrocatalytic oxidation for monoamines and their metabolites with relatively high sensitivity, stability, and long life. Nerve cells were primarily cultured. EMI was radiated to three experimental model nerve cells: (i) on mature nerve cells, (ii) on the culture medium, and (iii) on juvenile nerve cells for various periods of time. Then the levels of monoamines in the culture medium were detected by high-performance liquid chromatography-electrochemical detection. The data indicated that electromagnetic fields could influence neurotransmitter metabolism by direct effect on nerve cells or effect on the nutrient medium and that the effect was not only relevant with the length of radiation time, but also with the growing state of the nerve cells. PMID:12137776

Xu, Fang; Gao, Mengnan; Wang, Lin; Jin, Litong

2002-08-01

253

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

Directory of Open Access Journals (Sweden)

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

254

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

Science.gov (United States)

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

255

Projections of Low Spontaneous Rate, High Threshold Auditory Nerve Fibers to the Small Cell Cap of the Cochlear Nucleus in Cats  

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The marginal shell of the anteroventral cochlear nucleus houses small cells that are distinct from the overlying microneurons of the granule cell domain and the underlying projection neurons of the magnocellular core. This thin shell of small cells and associated neuropil receives auditory nerve input from only the low (<18 s/s) spontaneous rate (SR), high threshold auditory nerve fibers; high SR, low threshold fibers do not project there. It should be noted, however, that most of these audit...

Ryugo, D. K.

2008-01-01

256

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

Science.gov (United States)

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

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

2014-01-01

257

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

Scientific Electronic Library Online (English)

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

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

258

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

Directory of Open Access Journals (Sweden)

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

259

Trigger point-related sympathetic nerve activity in chronic sciatic leg pain: a case study.  

Science.gov (United States)

Sciatica has classically been associated with irritation of the sciatic nerve by the vertebral disc and consequent inflammation. Some authors suggest that active trigger points in the gluteus minimus muscle can refer pain in similar way to sciatica. Trigger point diagnosis is based on Travel and Simons criteria, but referred pain and twitch response are significant confirmatory signs of the diagnostic criteria. Although vasoconstriction in the area of a latent trigger point has been demonstrated, the vasomotor reaction of active trigger points has not been examined. We report the case of a 22-year-old Caucasian European man who presented with a 3-year history of chronic sciatic-type leg pain. In the third year of symptoms, coexistent myofascial pain syndrome was diagnosed. Acupuncture needle stimulation of active trigger points under infrared thermovisual camera showed a sudden short-term vasodilatation (an autonomic phenomenon) in the area of referred pain. The vasodilatation spread from 0.2 to 171.9?cm(2) and then gradually decreased. After needling, increases in average and maximum skin temperature were seen as follows: for the thigh, changes were +2.6°C (average) and +3.6°C (maximum); for the calf, changes were +0.9°C (average) and +1.4°C (maximum). It is not yet known whether the vasodilatation observed was evoked exclusively by dry needling of active trigger points. The complex condition of the patient suggests that other variables might have influenced the infrared thermovision camera results. We suggest that it is important to check if vasodilatation in the area of referred pain occurs in all patients with active trigger points. PMID:24970043

Skorupska, El?bieta; Rychlik, Micha?; Pawelec, Wiktoria; Bednarek, Agata; Samborski, W?odzimierz

2014-10-01

260

Tear fluid hyperosmolality increases nerve impulse activity of cold thermoreceptor endings of the cornea.  

Science.gov (United States)

Dry eye disease (DED) is a multifactorial disorder affecting the composition and volume of tears. DED causes ocular surface dryness, cooling, and hyperosmolality, leading ultimately to corneal epithelium damage and reduced visual performance. Ocular discomfort is the main clinical symptom in DED. However, the peripheral neural source of such unpleasant sensations is still unclear. We analyzed in excised, superfused mouse eyes, the effect of NaCl-induced hyperosmolality (325-1005 mOsm·kg(-1)) on corneal cold thermoreceptor and polymodal nociceptor nerve terminal impulse (NTI) activity. Osmolality elevations at basal corneal temperature (33.6°C) linearly increased the ongoing NTI frequency of cold thermoreceptors, at a mean rate of 0.34 imp·s(-1)/10 mOsm. This frequency increase became significant with osmolality values greater than 340 mOsm. Comparison of cold thermoreceptor activity increase induced by a dynamic temperature reduction of 1.8°C under iso- and hyperosmolal (360-mOsm) conditions provided evidence that more than 50% of the increased firing response was attributable to hyperosmolality. Comparatively, activation of corneal polymodal nociceptor endings by hyperosmolal solutions started with values of 600 mOsm and greater. Sensitization of polymodal nociceptors by continuous perfusion with an "inflammatory soup" (bradykinin, histamine, prostaglandin E2 [PGE2], serotonin, and adenosine triphosphate [ATP]) did not enhance their activation by hyperosmolal solutions. High osmolality also altered the firing pattern and shape of cold and polymodal NTIs, possibly reflecting disturbances in local membrane currents. Results strongly suggest that tear osmolality elevations in the range observed in DED predominantly excite cold thermoreceptors, supporting the hypothesis that dryness sensations experienced by these patients are due, at least in part, to an augmented activity of corneal cold thermoreceptors. PMID:24785271

Parra, Andres; Gonzalez-Gonzalez, Omar; Gallar, Juana; Belmonte, Carlos

2014-08-01

 
 
 
 
261

Nerves and Anesthesia: A physics perspective on medicine  

CERN Document Server

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

Heimburg, Thomas

2014-01-01

262

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

263

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. PMID:24895582

van Neerven, Sabien G A; Krings, Laura; Haastert-Talini, Kirsten; Vogt, Michael; Tolba, René H; Brook, Gary; Pallua, Norbert; Bozkurt, Ahmet

2014-01-01

264

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. PMID:24915536

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

2014-01-01

265

An analog VLSI implementation of the inner hair cell and auditory nerve using a dual AGC model.  

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An analog inner hair cell and auditory nerve circuit using a dual AGC model has been implemented using 0.35 micron mixed-signal technology. A fully-differential current-mode architecture is used and the ability to correct channel mismatch is evaluated with matched layouts as well as with digital current tuning. The Meddis test paradigm is used to examine the analog implementation's auditory processing capabilities and investigate the circuit's ability to correct DC mismatch. The correction techniques used demonstrate the analog inner hair cell and auditory nerve circuit's potential use in low-power, multiple-sensor analog biomimetic systems with highly reproducible signal processing blocks on a single massively parallel integrated circuit. PMID:24875284

Freedman, David S; Cohen, Howard I; Deligeorges, Socrates; Karl, Christian; Hubbard, Allyn E

2014-04-01

266

Central Muscarinic Cholinergic Activation Alters Interaction between Splenic Dendritic Cell and CD4+CD25- T Cells in Experimental Colitis  

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Background The cholinergic anti-inflammatory pathway (CAP) is based on vagus nerve (VN) activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR) signaling. Inflammatory bowel disease (IBD) patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs) and sequential CD4+/CD25?T cell activation in the context of experimental colitis. Methods The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 muscarinic acetylcholine receptor agonist McN-A-343 was used to activate CAP and vagus nerve and/or splenic nerve transection were performed. In addition, the role of ?7nAChR signaling and the NF-kB pathway was studied. Serum amyloid protein (SAP)-A, colonic tissue cytokines, IL-12p70 and IL-23 in isolated splenic DCs, and cytokines levels in DC-CD4+CD25?T cell co-culture were determined. Results McN-A-343 treatment reduced colonic inflammation associated with decreased pro-inflammatory Th1/Th17 colonic and splenic cytokine secretion. Splenic DCs cytokine release was modulated through ?7nAChR and the NF-kB signaling pathways. Cholinergic activation resulted in decreased CD4+CD25?T cell priming. The anti-inflammatory efficacy of central cholinergic activation was abolished in mice with vagotomy or splenic neurectomy. Conclusions Suppression of splenic immune cell activation and altered interaction between DCs and T cells are important aspects of the beneficial effect of brain activation of the CAP in experimental colitis. These findings may lead to improved therapeutic strategies in the treatment of IBD. PMID:25295619

Pavlov, Valentin A.; Tracey, Kevin J.; Khafipour, Ehsan; Ghia, Jean-Eric

2014-01-01

267

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

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

Fornaro Michele

2010-02-01

268

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

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

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

2010-01-01

269

Nerve growth factor and ras regulate ?-amyloid precursor protein gene expression in PC12 cells  

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The ?-amyloid protein, the major component of the vascular and plaque amyloid deposits that characterize Alzheimer's disease, derives from a larger ?-amyloid precursor protein (APP) that is expressed in both neural and nonneural cells. An increased expression of APP might actively contribute to the development of the pathology; however, the mechanisms involved in the regulation of APP gene expression are not yet well understood. In PC12 cells, a rat pheochromocytoma cell line, we have demon...

Cosgaya, Jose? Miguel; Latasa, Mari?a Jesu?s; Pascual, A?ngel

1996-01-01

270

Cardiovascular and renal complications of type 2 diabetes in obesity: role of sympathetic nerve activity and insulin resistance.  

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Overweight and obesity is a growing "world-wide epidemic problem". Because as many as, two-thirds of the adult population and a growing number of children are overweight. The prevalence of diabetes, especially type 2 diabetes and hypertension have significantly increased with the prevalence of obesity. Obesity accompanying type 2 diabetes and hypertension are known to be closely linked with insulin resistance and elevated sympathetic nervous activity. It has been well documented that obesity, hypertension, and diabetes are high risk factors for subsequent cardiovascular and renal complications. Many patients are both diabetic and hypertensive, while they are obese, but not all diabetic patients have hypertension, indicating that insulin resistance is not only a mechanism for blood pressure elevation in diabetic-hypertensive patients. Several investigators have reported that sympathetic nervous activation relates to cardiovascular complications in patients with hypertension, diabetes, and obesity, and that sympathetic nerve activity accompanying insulin resistance is closely linked with left ventricular hypertrophy in healthy subjects. In addition, sympathetic nerve activation may predict future renal injury in healthy normotensive subjects. These findings suggest that elevated sympathetic nerve activity associated with insulin resistance may contribute to the onset and maintenance of cardiovascular and renal complications in diabetes, and hypertension in obesity. Further, genetic polymorphisms of the beta2- and beta3-adrenoceptor gene have been associated with type-2 diabetes and insulin resistance in many epidemiological studies and might be another factor responsible for the close relationship between insulin resistance and heightened sympathetic nerve activity. Thus, focusing on the interactions between insulin resistance, sympathetic nervous activity and beta-adrenoceptor polymorphisms might help in understanding the precise relationships between insulin resistance and sympathetic nerve activity in type 2 diabetes and obesity-related hypertension. The purpose of this article is to provide a synthesis of the current findings on the mechanisms of the onset and maintenance of cardiovascular and renal complications in obesity, diabetes and hypertension. A better understanding of the relationships of sympathetic nervous system activity and insulin resistance might help with the clinical treatment of diabetes and hypertension in obesity. Further, to clarify the pathogenesis and mechanisms of the association between obesity, diabetes, and hypertension may lead to reductions in cardiovascular and renal risk. PMID:20034369

Masuo, Kazuko; Rakugi, Hiromi; Ogihara, Toshio; Esler, Murray D; Lambert, Gavin W

2010-03-01

271

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

272

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

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Malignant peripheral nerve sheath tumors (MPNST) derive from the Schwann cell or perineurial cell lineage and occur either sporadically or in association with the tumor syndrome neurofibromatosis type 1 (NF1). MPNST often pose a diagnostic challenge due to their frequent lack of pathognomonic morphological or immunohistochemical features. Mutations in the NF1 tumor suppressor gene are found in all NF1-associated and many sporadic MPNST. The presence of NF1 mutation may have the potential to differentiate MPNST from several morphologically similar neoplasms; however, mutation detection is hampered by the size of the gene and the lack of mutational hot spots. Here we describe a newly developed monoclonal antibody binding to the C-terminus of neurofibromin (clone NFC) which was selected for optimal performance in routinely processed formalin-fixed and paraffin-embedded tissue. NFC immunohistochemistry revealed loss of neurofibromin in 22/25 (88 %) of NF1-associated and 26/61 (43 %) of sporadic MPNST. There was a strong association of neurofibromin loss with deletions affecting the NF1 gene (P < 0.01). In a series of 256 soft tissue tumors of different histotypes NFC staining showed loss of neurofibromin in 2/8 myxofibrosarcomas, 2/12 (16 %) pleomorphic liposarcomas, 1/16 (6 %) leiomyosarcomas, and 4/28 (14 %) unclassified undifferentiated pleomorphic sarcomas. However, loss of neurofibromin was not observed in 22 synovial sarcomas, 27 schwannomas, 23 solitary fibrous tumors, 14 low-grade fibromyxoid sarcomas, 50 dedifferentiated liposarcomas, 27 myxoid liposarcomas, 13 angiosarcomas, 9 extraskeletal myxoid chondrosarcomas, and 7 epitheloid sarcomas. Immunohistochemistry using antibody NFC may substantially facilitate sarcoma research and diagnostics. PMID:24464231

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

2014-04-01

273

Schwann Cell Engraftment Into Injured Peripheral Nerve Prevents Changes in Action Potential Properties  

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Peripheral nerve injury results in changes in action potential waveform, ion channel organization, and firing properties of primary afferent neurons. It has been suggested that these changes are the result of reduction in basal trophic support from skin targets. Subcutaneous injections of Fluro-Gold (FG) in the hind limb of the rat were used to identify cutaneous primary afferent neurons. Five days after FG injection, sciatic nerves were ligated and encapsulated in a silicon tube allowing neu...

Yu, Kewei; Kocsis, Jeffery D.

2005-01-01

274

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

275

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

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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

276

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

277

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

Science.gov (United States)

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

Carlyon, Robert P; Deeks, John M

2013-01-01

278

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

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Recent studies report that the menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women. The purpose of the present study was to determine whether oral contraceptives (OC) influence sympathetic neural activation during an orthostatic challenge. Based on evidence that sympathetic baroreflex sensitivity (BRS) is increased during the “low hormone” (LH) phase (i.e., placebo pills) in women taking OC, we hypothesized an augmented muscle sympathetic nerve activity (MSNA) response to orthostatic stress during the LH phase. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP; ?5, ?10, ?15, ?20, ?30, ?40 mmHg; 3 min/stage) in 12 healthy women taking OC (age 22 ± 1 years). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA. Subjects were examined twice: once during LH phase and once ?3 wk after LH during the “high hormone” phase (randomized order). Resting MSNA (10 ± 2 vs. 13 ± 2 bursts/min), MAP (85 ± 3 vs. 84 ± 3 mmHg), and HR (62 ± 2 vs. 65 ± 3 beats/min) were not different between phases. MSNA and HR increased during progressive LBNP (P < 0.001), and these increases were similar between phases. Progressive LBNP did not change MAP during either phase. Sympathetic BRS increased during progressive LBNP, but these responses were not different between LH and high hormone phases. In conclusion, our results demonstrate that OCs do not alter cardiovascular and sympathetic neural responses to an orthostatic challenge in young, healthy women. PMID:19828840

Klein, Jenna C.; Schwartz, Christopher E.

2010-01-01

279

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

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

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

2009-12-01

280

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

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

Shang Yuze

2008-04-01

 
 
 
 
281

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

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

Neubauer, Heinrich; Köppl, Christine; Heil, Peter

2009-06-01

282

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

International Nuclear Information System (INIS)

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

283

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

284

Rapid sprouting of filopodia in nerve terminals of chromaffin cells, PC12 cells, and dorsal root neurons induced by electrical stimulation.  

Science.gov (United States)

Rapid morphological changes induced by direct electrical stimulation of nerve terminals were studied by using video-enhanced differential interference contrast microscopy at a very high magnification (12,000x). We used mainly cultured bovine chromaffin cells, which developed neurite-like processes, and PC12 cells, which showed neuronal differentiation upon NGF treatment. In a few cases, primary neurons of the rat dorsal root ganglion were also examined. Brief pulse stimulation of the terminals and varicosities induced exocytosis accompanied by rapid formation of filopodia. These filopodia, 0.1-0.2 micron in diameter and up to 10 microns in length, formed within a few hundreds of milliseconds and then retracted within tens of seconds. They could also be induced by K depolarization. This rapid filopodial sprouting strongly depended on the presence of extracellular Ca2+ and could be abolished in a medium containing a Ca chelator (EGTA) or La2+. Anti-cytoskeletal agents colchicine and cytochalasin B failed to block this response completely but lidocaine fully suppressed it. Quantitative analysis of exocytosis and filopodial sprouting showed that they were independent events, not directly linked to each other, having different thresholds usually higher for filopodial formation. In PC12 cells, the extent of filopodial sprouting varied with the state of differentiation of the cells, suggesting a functional role of rapid sprouting during a particular phase of their differentiation. Filopodia could be induced with greater ease by repetitive stimulation. The same responses may occur at growth cones approaching the target cells or even at mature synapses particularly after repetitive electrical activity, possibly playing a role in use-dependent synapse formation or plasticity. PMID:7931553

Manivannan, S; Terakawa, S

1994-10-01

285

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

Science.gov (United States)

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

Watkins, Trent A; Scholze, Anja R

2014-01-01

286

Nerve growth factor inhibits the synthesis of a single-stranded DNA binding protein in pheochromocytoma cells (clone PC12).  

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Arrest of mitosis and neurite outgrowth induced by nerve growth factor (NGF) in rat pheochromocytoma cells (clone PC12) is accompanied by a progressive inhibition of the synthesis of a protein that binds to single-stranded but not to double-stranded DNA. Time course experiments show that this inhibition is already apparent after a 2-day incubation with NGF and is maximum (85-95%) upon achievement of complete PC12 cell differentiation. Inhibition of the synthesis of this single-stranded DNA bi...

Biocca, S.; Cattaneo, A.; Calissano, P.

1984-01-01

287

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

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

Milbrandt, J.

1986-01-01

288

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

Science.gov (United States)

Neurotrophins (NTs) control neuron survival and regeneration. Recent research showed that NTs possess cardiovascular actions. In this study, we investigated the hypothesis that the NT nerve growth factor (NGF) prevents cardiomyocyte apoptosis. We demonstrated that cultured rat neonatal cardiomyocytes (RNCMs) produce NGF and express its trkA (tropomyosin-related receptor A (NGF high-affinity receptor)) receptor. RNCMs given a neutralizing antibody for NGF or the trkA inhibitor K252a underwent apoptosis, thus suggesting that NGF is an endogenous prosurvival factor for cardiomyocytes. Adenovirus (Ad)-mediated NGF overexpression protected RNCMs from apoptosis induced by either hypoxia/reoxygenation or angiotensin II (AngII). Similarly, recombinant NGF inhibited AngII-induced apoptosis in isolated rat adult cardiomyocytes. Finally, in a rat model of myocardial infarction, NGF gene transfer promoted cardiomyocyte survival. In RNCMs, recombinant NGF induced trkA phosphorylation, followed by Ser473 phosphorylation and nuclear translocation of phospho-protein kinase B (Akt). In response to Akt activation, Forkhead transcription factors Foxo-3a and Foxo-1 were phosphorylated and excluded from the nucleus. The prosurvival effect of adenoviral vector carrying the human NGF gene was inhibited in vitro by K252a, LY294002 (a pan-phosphatidyl inositol 3-kinase - PI3K - inhibitor), an Akt small interfering RNA, and adenoviruses carrying a dominant negative mutant form of Akt (Ad.DN.Akt) or an Akt-resistant Foxo-3a (Ad.AAA-Foxo-3a). These results newly demonstrate the cardiac prosurvival action of NGF and provide mechanistic information on the signaling pathway, which encompasses trkA, PI3K-Akt, and Foxo. PMID:17992191

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

2008-02-01

289

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

290

Facilitation by P(2) receptor activation of acetylcholine release from rat motor nerve terminals: interaction with presynaptic nicotinic receptors.  

Science.gov (United States)

ATP is released from motor nerve endings together with acetylcholine. Released adenine nucleotides can be extracellularly metabolized into adenosine, which is a presynaptic neuromodulator at neuromuscular junctions, but it is not known if P(2) receptor activation also modulates acetylcholine release from mature motor nerve endings. We now tested the effect of a stable ATP analogue, beta,gamma-imido ATP on the nerve-evoked release of acetylcholine from adult rat hemidiaphragm preparations. beta,gamma-Imido ATP (10-100 microM) facilitated in a concentration-dependent manner evoked acetylcholine release, and 30 microM beta,gamma-imido ATP caused a 125% facilitation of evoked acetylcholine release. This facilitatory effect of beta,gamma-imido ATP (30 microM) was abolished by the P(2) receptor antagonists, suramin (100 microM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 microM), but not by the A(1) or A(2A) adenosine receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (50 nM) and ZM 241385 (50 nM), respectively. The facilitation of acetylcholine release by beta, gamma-imido ATP (30 microM) was also prevented by the nicotinic acetylcholine receptor antagonist, D-tubocurarine (1 microM) and the facilitatory effect (40%) of the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (1 microM) was abolished by PPADS (10 microM). These results demonstrate a presynaptic facilitatory effect of P(2) receptor activation at the rat phrenic nerve endings, which is tightly coupled with the presynaptic nicotinic autofacilitatory system. PMID:10986338

Salgado, A I; Cunha, R A; Ribeiro, J A

2000-09-22

291

Time sequence of auditory nerve and spiral ganglion cell degeneration following chronic kanamycin-induced deafness in the guinea pig.  

Science.gov (United States)

We investigated the time sequence of morphological changes of the spiral ganglion cell (SGC) and auditory nerve (AN) following chronic kanamycin-induced deafness. Guinea pigs were treated with kanamycin by subcutaneous injection at 500 mg/kg per day for 7 days. Histological changes in hair cells, SGCs, Schwann cells and the area of the cross-sectional of the AN with vestibular ganglion (VG) in the internal acoustic meatus were quantified at 1, 7, 14, 28, 56 and 70 days after kanamycin treatment. Outer hair cells decreased at 7 and 14 days. Loss of inner hair cells occurred at 14 and 28 days. The cross-sectional area of the AN with VG increased at 1 day and decreased shortly following loss of SGCs and Schwann cells at 7, 14 and 28 days after deafening. There was a similar time course of morphological changes in the overall cochlea and the basal turn. Thus, the effects of kanamycin on hair cells, spiral ganglion and Schwann cells are progressive. Early degeneration of SGC and Schwann cell mainly results from the direct toxic effect of kanamycin. However, multiple factors such as loss of hair cell, degeneration of Schwann cell and the progressive damage of kanamycin, may participate in the late degeneration process of SGCs. The molecular mechanism of the degeneration of SGC and Schwann cell should be investigated in the future. Moreover, there is a different time sequence of cell degeneration between acute and chronic deafness by kanamycin. PMID:20202466

Kong, W J; Yin, Z D; Fan, G R; Li, D; Huang, X

2010-05-17

292

Forelimb muscle activity following nerve graft repair of ventral roots in the rat cervical spinal cord.  

Science.gov (United States)

Current research on the cellular mechanisms of nerve regeneration suggests the application of nerve growth factors at the repair sites to be beneficial. To test the effectiveness of this approach, we performed transections of the C6 and C7 ventral rootlets from their original sites in the spinal cord of 18 rats. We investigated the electrophysiological changes in three groups of rats operated on by different repair strategies. Six rats comprised the control group (G1). In the other 12 rats, 24 rootlets were implanted into the spinal cord by means of an intercostal nerve graft through the pia mater immediately after transection. Six rats (G2) had fibrin glue applied at the incision. The last 6 rats (G3) had grafts with acidic fibroblast growth factor (aFGF) added to the fibrin glue. The rats' functional recovery was evaluated electrophysiologically at 6 weeks and 6 months after the operation. Needle electromyography showed profound fibrillation potentials (Daube's scoring system) in the deltoid, biceps, and triceps of the operated forelimbs in all groups 6 weeks after the operation. After 6 months, there was a significant decrease in the amount of fibrillation potentials in all groups (G1, G2 and G3, p ratio in G2 = 51.8316, G3 = 57.4262, generalized estimating equation). We conclude that several cervical roots can regenerate through intercostal nerve grafts applied using fibrin glue. Adding aFGF may increase the efficacy of sprouting. PMID:12052433

Chuang, Tien-Yow; Huang, Ming-Chao; Chen, Kuo-Chih; Chang, Yue-Cune; Yen, Yu-Shu; Lee, Liang-Shong; Cheng, Henrich

2002-06-21

293

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

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

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

2008-01-01

294

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

International Nuclear Information System (INIS)

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

295

Transplantation of a temperature-sensitive, nerve growth factor-secreting, neuroblastoma cell line into adult rats with fimbria-fornix lesions rescues cholinergic septal neurons.  

Science.gov (United States)

The HT4 cell line was derived from infection of a mouse neuroblastoma cell line with a retrovirus that encoded the temperature-sensitive (ts) mutant of SV40 large T antigen. At nonpermissive temperature, HT4 cells differentiated with neuronal morphology, expressed neuronal antigens, synthesized nerve growth factor (NGF) mRNA, and secreted biologically active NGF in vitro. We sought to establish whether transplanted HT4 cells expressed class I major histocompatibility complex (MHC) antigens, a partial requirement for recognition by cytotoxic T lymphocytes (CTL), and thus be susceptible to xenograft rejection. Differentiated HT4 cells expressed marginally detectable levels of class I MHC antigens, but demonstrated higher levels of class I MHC expression after treatment with interferon-gamma. However, HT4 cells were resistant to direct lysis by perforin, the pore-forming protein of CTLs, and thus may have potential use in xenograft experiments. To address whether HT4 cells secrete NGF in vivo, HT4 cells were transplanted into adults rats with unilateral fimbria-fornix transections. A ts cell line derived from P4 cerebellum, BT1, that does not differentiate with neuronal phenotype or synthesize NGF in vitro, was transplanted as a control. Six weeks posttransplant. HT4 cells had integrated into host CNS without forming tumors. In BT1 transplants, the number of medial septal acetylcholinesterase (AChE)-positive cells was reduced to 26-39% of the contralateral control side, depending on the rostrocaudal level. In HT4 transplants, the number of cholinergic septal neurons was 58-78% of the contralateral side. This percentage was significantly (P less than 0.005) greater than that seen with BT1 transplants, indicating that transplanted HT4 cells secrete NGF in vivo and rescue cholinergic septal neurons following fimbria-fornix transection. PMID:2033646

Whittemore, S R; Holets, V R; Keane, R W; Levy, D J; McKay, R D

1991-02-01

296

Inhibition of Abl tyrosine kinase enhances nerve growth factor-mediated signaling in Bcr-Abl transformed cells via the alteration of signaling complex and the receptor turnover.  

Science.gov (United States)

Receptor tyrosine kinase-mediated signaling is tightly regulated by a number of cytoplasmic signaling molecules. In this report, we show that Bcr-Abl transformed chronic myelogenous leukemia (CML) cell lines, K562 and Meg-01, express the receptor for nerve growth factor (NGF), TrkA, on the cell surface; however, the NGF-mediated signal is not particularly strong. Treatment with imatinib, a potent inhibitor of Bcr-Abl tyrosine kinase, downmodulates phosphorylation of downstream molecules. Upon stimulation with NGF, Erk and Akt are phosphorylated to a much greater degree in imatinib-treated cells than in untreated cells. Knockdown of expression of Bcr-Abl using small interfering RNA technique also enhanced NGF-mediated Akt phosphorylation, indicating that Bcr-Abl kinase modifies NGF signaling directly. Imatinib treatment also enhanced NGF signaling in rat adrenal pheochromocytoma cell line PC12 that expresses TrkA and c-Abl, suggesting that it is not only restoration of responsiveness to NGF after blocking oncoprotein activity, but also c-Abl tyrosine kinase per se may be a negative regulator of growth factor signaling. Furthermore, inhibition of Abl tyrosine kinase enhanced clearance of surface TrkA after NGF treatment and simultaneously enhanced NGF-mediated signaling, suggesting that as in neuronal cells 'signaling endosomes' are formed in hematopoietic cells. To examine the role of TrkA in CML cells, we studied cell growth or colony formation in the presence or absence of imatinib with or without NGF. We found that NGF treatment induces cell survival in imatinib-treated CML cell lines, as well as colony formation of primary CD34+ CML cells, strongly suggesting that NGF/TrkA signaling contributes to aberrant signaling in CML. PMID:18427551

Koch, A; Scherr, M; Breyer, B; Mancini, A; Kardinal, C; Battmer, K; Eder, M; Tamura, T

2008-08-01

297

Quasi-trapezoidal pulses to selectively block the activation of intrinsic laryngeal muscles during vagal nerve stimulation  

Science.gov (United States)

The stimulation of the vagus nerve has been used as an anti-epileptic treatment for over a decade, and its use for depression and chronic heart failure is currently under investigation. Co-activation of the intrinsic laryngeal muscles may limit the clinical use of vagal stimulation, especially in the case of prolonged activation. To prevent this, the use of a selective stimulation paradigm has been tested in seven acute pig experiments. Quasi-trapezoidal pulses successfully blocked the population of the largest and fastest vagal myelinated fibers being responsible for the co-activation. The first response in the vagus compound action potential was reduced by 75 ± 22% (mean ± SD) and the co-activated muscle action potential by 67 ± 25%. The vagal bradycardic effects remained unchanged during the selective block, confirming the leading role of thin nerve fibers for the vagal control of the heart. Quasi-trapezoidal pulses may be an alternative to rectangular pulses in clinical vagal stimulation when the co-activation of laryngeal muscles must be avoided.

Tosato, M.; Yoshida, K.; Toft, E.; Struijk, J. J.

2007-09-01

298

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

299

Terminal nerve: cranial nerve zero  

Directory of Open Access Journals (Sweden)

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

Jorge Eduardo Duque Parra

2006-12-01

300

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

Scientific Electronic Library Online (English)

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

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

 
 
 
 
301

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

CERN Document Server

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

Shneider, M N

2014-01-01

302

Cyclo-oxygenase and lipoxygenase pathways in mast cell dependent-neurogenic inflammation induced by electrical stimulation of the rat saphenous nerve.  

Science.gov (United States)

1. We investigated the role of arachidonic acid metabolism and assessed the participation of mast cells and leukocytes in neurogenic inflammation in rat paw skin. We compared the effect of lipoxygenase (LOX) and cyclo-oxygenase (COX) inhibitors on oedema induced by saphenous nerve stimulation, substance P (SP), and compound 48/80. 2. Intravenous (i.v.) pre-treatment with a dual COX/LOX inhibitor (RWJ 63556), a dual LOX inhibitor/cysteinyl-leukotriene (CysLt) receptor antagonist (Rev 5901), a LOX inhibitor (AA 861), a five-lipoxygenase activating factor (FLAP) inhibitor (MK 886), or a glutathione S-transferase inhibitor (ethacrynic acid) significantly inhibited (40 to 60%) the development of neurogenic oedema, but did not affect cutaneous blood flow. Intradermal (i.d.) injection of LOX inhibitors reduced SP-induced oedema (up to 50% for RWJ 63556 and MK 886), whereas ethacrynic acid had a potentiating effect. 3. Indomethacin and rofecoxib, a highly selective COX-2 inhibitor, did not affect neurogenic and SP-induced oedema. Surprisingly, the structurally related COX-2 inhibitors, NS 398 and nimesulide, significantly reduced both neurogenic and SP-induced oedema (70% and 42% for neurogenic oedema, respectively; 49% and 46% for SP-induced oedema, respectively). 4. COX-2 mRNA was undetectable in saphenous nerves and paw skin biopsy samples, before and after saphenous nerve stimulation. 5. A mast cell stabilizer, cromolyn, and a H(1) receptor antagonist, mepyramine, significantly inhibited neurogenic (51% and 43%, respectively) and SP-induced oedema (67% and 63%, respectively). 6. The co-injection of LOX inhibitors and compound 48/80 did not alter the effects of compound 48/80. Conversely, ethacrynic acid had a significant potentiating effect. The pharmacological profile of the effect of COX inhibitors on compound 48/80-induced oedema was similar to that of neurogenic and SP-induced oedema. 7. The polysaccharide, fucoidan (an inhibitor of leukocyte rolling) did not affect neurogenic or SP-induced oedema. 8. Thus, (i) SP-induced leukotriene synthesis is involved in the development of neurogenic oedema in rat paw skin; (ii) this leukotriene-mediated plasma extravasation might be independent of mast cell activation and/or of the adhesion of leukocytes to the endothelium; (iii) COX did not appear to play a significant role in this process. PMID:11264253

Le Filliatre, G; Sayah, S; Latournerie, V; Renaud, J F; Finet, M; Hanf, R

2001-04-01

303

The effect of poly(3-hydroxybutyrate-co-3- hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cell (hMSC) on axonal regeneration in experimental sciatic nerve damage.  

Science.gov (United States)

This study is designed to evaluate the treatment effect of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cells (hMSC) on axonal regeneration in experimental rat sciatic nerve damage, and compare the results of this modality with autologous nerve grafting. In Spraque-Dawley albino rats, 10-mm-long experimental nerve gaps were created. Three groups were constituted, the gap was repaired with autologous nerve graft (autograft group), PHBHHx nerve graft alone (PHBHHx alone group), and PHBHHx nerve graft with hMSCs inside (PHBHHx with hMSC group), respectively. The results were evaluated with functional recovery, electrophysiological evaluation, and histological evaluation either with light microscopy and transmission electron microscopy for axonal regeneration and myelin formation. In functional evaluation, autograft and PHBHHx with hMSC groups showed functional improvement with time, whereas PHBHHx alone group did not. Electrophysiological evaluation showed better results in autograft and PHBHHx with hMSC groups when compared to PHBHHx alone group. There was no statistical difference between autograft and PHBHHx with hMSC groups. Histological evaluation showed regenerated axons in each group. Autograft group was better than the others, and PHBHHx with hMSC group was better than PHBHHx alone group both for axonal regeneration and myelin formation. This study showed that the nerve grafts which were prepared from PHBHHx with oriented nanofiber three-dimensional surfaces aided to nerve regeneration, either used alone or with hMSC. PHBHHx provided better nerve regeneration when used with hMSCs inside than alone, and reached the same statistical treatment effect in functional evaluation and electrophysiological evaluation when compared to autografting. PMID:24350993

Sakar, Mustafa; Korkusuz, Petek; Demirbilek, Murat; Cetinkaya, Duygu Uçkan; Arslan, Sevil; Denkba?, Emir Baki; Temuçin, Ça?r? Mesut; Bilgiç, Elif; Hazer, Derya Burcu; Bozkurt, Gökhan

2014-09-01

304

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

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

Xie Jining; Chen Linfeng; Varadan, Vijay K [Nanomaterials and Nanotubes Research Laboratory, College of Engineering, University of Arkansas, Fayetteville, AR 72701 (United States); Yancey, Justin; Srivatsan, Malathi [Department of Biological Sciences, Arkansas State University, State University, AR 72467 (United States)], E-mail: jxie@uark.edu, E-mail: msrivatsan@astate.edu

2008-03-12

305

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

Science.gov (United States)

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

Xie, Jining; Chen, Linfeng; Varadan, Vijay K.; Yancey, Justin; Srivatsan, Malathi

2008-03-01

306

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

International Nuclear Information System (INIS)

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

307

Perineural cell tumor. Immunocytochemical and ultrastructural characterization. Relationship to other peripheral nerve tumors with a review of the literature.  

Science.gov (United States)

A perineurial cell tumor occurred in the shoulder girdle of a 47 year old woman. Light microscopy demonstrated a well-differentiated spindle-cell neoplasm of uncertain histogenesis. Immunocytochemical staining for S-100 protein was negative. Ultrastructural study revealed tumor cells with characteristics of perineurium, e.g. large numbers of micropinocytotic vesicles, numerous intercellular junctions, and elongated cell processes surrounded by basal lamina. Tumors of perineurial cells should be distinguished from the commonly recognized schwannomas as well as from various soft tissue lesions so that their biologic behavior can be better defined. A review of three other reported cases of perineurial cell tumors suggested that these tumors are benign and are usually located in the extremities and shoulder girdle. In addition, perineurial cell proliferation has been identified in other lesions of peripheral nerves, such as neurofibromas and localized hypertrophic neuropathy. Immunocytochemical and ultrastructural study of spindle-cell lesions with unusual histologic features may reveal that perineurial cell proliferation occurs more frequently than currently recognized. PMID:3080843

Weidenheim, K M; Campbell, W G

1986-01-01

308

VEGF-A165 potently induces human blood-nerve barrier endothelial cell proliferation, angiogenesis and wound healing in vitro  

Science.gov (United States)

Several mitogens such as vascular endothelial growth factor (VEGF) have been implicated in mammalian vascular proliferation and repair. However, the molecular mediators of human blood-nerve barrier (BNB) development and specialization are unknown. Primary human endoneurial endothelial cells (pHEndECs) were expanded in vitro and specific mitogen receptors detected by western blot. pHEndECs were cultured with basal medium containing different mitogen concentrations with or without heparin. Non-radioactive cell proliferation, Matrigel™-induced angiogenesis and sterile micropipette injury wound healing assays were performed. Proliferation rates, number and total length of induced microvessels and rate of endothelial cell monolayer wound healing were determined and compared to basal conditions. VEGF-A165 in the presence of heparin, was the most potent inducer of pHEndEC proliferation, angiogenesis and wound healing in vitro. 1.31 nM VEGF-A165 induced ~110% increase in cell proliferation relative to basal conditions (~51% without heparin). 2.62 pM VEGF-A165 induced a 3-fold increase in mean number of microvessels and 3.9-fold increase in total capillary length/field relative to basal conditions. In addition, 0.26 nM VEGF-A165 induced ~1.3-fold increased average rate of endothelial wound healing 4–18 hours after endothelial monolayer injury, mediated by increased cell migration. VEGF-A165 was the only mitogen capable of complete wound closure, occurring within 30 hours following injury via increased cell proliferation. This study demonstrates that VEGF-A165, in the presence of heparin, is a potent inducer of pHEndEC proliferation, angiogenesis and wound healing in vitro. VEGF-A165 may be an important mitogen necessary for human BNB development and recovery in response to peripheral nerve injury. PMID:23712256

Reddy, Chetan Lakshmana; Yosef, Nejla; Ubogu, Eroboghene E.

2013-01-01

309

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

DEFF Research Database (Denmark)

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

Jolivalt, CG; Fineman, M

2011-01-01

310

Cannabinoid and GABA modulation of sympathetic nerve activity and blood pressure in the dorsal periaqueductal gray of the rat.  

Science.gov (United States)

Sympathoexcitation and increased blood pressure evoked by central networks integrating defensive behavior are fundamental to the acute stress response. A balance between excitatory glutamatergic and inhibitory GABAergic neurotransmission in the dorsal periaqueductal gray (dPAG) results in a tonic level of activity in the alerting system. Neuromodulators such as endocannabinoids have been shown to influence the sympathoexcitatory and pressor components of acute stress in the dPAG, exemplified by the defense response as a model, but the mechanism of integration remains unknown. The present study examines the role of GABA and its interaction with endocannabinoids in modulating sympathetic nerve activity and blood pressure related to the defense response. Microinjection of the broad-spectrum excitatory amino acid dl-homocysteic acid (DLH) identified sites of the defense pathway in the dPAG from which an increase in renal sympathetic nerve activity and blood pressure could be evoked, and subsequent microinjections were made at the same site through a multibarrelled micropipette. Blockade of GABAA receptors or microinjection of the cannabinoid 1 receptor agonist anandamide elicited a renal sympathoexcitation and pressor response. Prior microinjection of the GABAA receptor antagonist gabazine attenuated the sympathoexcitation and pressor response associated with anandamide microinjection. In contrast, the sympathetic response to DLH was enhanced by GABAA receptor blockade. These data demonstrate that sympathoexcitatory neurons in the dPAG are under tonic inhibition by GABA and that endocannabinoids modulate this GABAergic neurotransmission to help regulate components of the defense response. PMID:21940402

Dean, C

2011-12-01

311

In vivo microdialysis and electroencephalographic activity in freely moving guinea pigs exposed to organophosphorus nerve agents sarin and VX: analysis of acetylcholine and glutamate.  

Science.gov (United States)

Organophosphorus nerve agents such as sarin (GB) and VX irreversibly inhibit acetylcholinesterase, causing a buildup of acetylcholine (ACh) in synapses and neuromuscular junctions, which leads to excess bronchial secretions, convulsions, seizures, coma, and death. Understanding the unique toxic characteristics of different nerve agents is vital in the effort to develop broad spectrum medical countermeasures. To this end, we employed a repeated measure multivariate design with striatal microdialysis collection and high-performance liquid chromatography analysis to measure changes in concentrations of several neurotransmitters (ACh, glutamate, aspartate, GABA) in the same samples during acute exposure to GB or VX in freely moving guinea pigs. Concurrent with microdialysis collection, we used cortical electrodes to monitor brain seizure activity. This robust double multivariate design provides greater fidelity when comparing data while also reducing the required number of subjects. No correlation between nerve agents' propensity for causing seizure and seizure-related lethality was observed. The GB seizure group experienced more rapid and severe cholinergic toxicity and lethality than that of the VX seizure group. Seizures generated from GB and VX exposure resulted in further elevation of ACh level and then a gradual return to baseline. Glutamate levels increased in the GB, but not in the VX, seizure group. There were no consistent changes in either aspartate or GABA as a result of either nerve agent. These observations reinforce findings with other nerve agents that seizure activity per se contributes to the elevated levels of brain ACh observed after nerve agent exposure. PMID:21695469

O'Donnell, John C; McDonough, John H; Shih, Tsung-Ming

2011-12-01

312

Identification of novel target genes of nerve growth factor (NGF in human mastocytoma cell line (HMC-1 (V560G c-Kit by transcriptome analysis  

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Full Text Available Abstract Background Nerve growth factor (NGF is a potent growth factor that plays a key role in neuronal cell differentiation and may also play a role in hematopoietic differentiation. It has been shown that NGF induced synergistic action for the colony formation of CD34 positive hematopoietic progenitor cells treated with macrophage-colony stimulating factor (M-CSF or CSF-1, or stem cell factor (SCF. However, the exact role of NGF in hematopoietic system is unclear. It is also not clear whether NGF mediated signals in hematopoietic cells are identical to those in neuronal cells. Results To study the signal transduction pathways induced by NGF treatment in hematopoietic cells, we utilized the mastocytoma cell line HMC-1(V560G c-Kit which expresses the NGF receptor, tropomyosin-receptor-kinase (TrkA, as well as the constitutively activated SCF receptor, V560G c-Kit, which can be inhibited completely by treatment with the potent tyrosine kinase inhibitor imatinib mesylate (imatinib. NGF rescues HMC-1(V560G c-Kit cells from imatinib mediated cell death and promotes proliferation. To examine the NGF mediated proliferation and survival in these cells, we compared the NGF mediated upregulated genes (30 and 120 min after stimulation to the downregulated genes by imatinib treatment (downregulation of c-Kit activity for 4 h by transcriptome analysis. The following conclusions can be drawn from the microarray data: Firstly, gene expression profiling reveals 50% overlap of genes induced by NGF-TrkA with genes expressed downstream of V560G c-Kit. Secondly, NGF treatment does not enhance expression of genes involved in immune related functions that were down regulated by imatinib treatment. Thirdly, more than 55% of common upregulated genes are involved in cell proliferation and survival. Fourthly, we found Kruppel-like factor (KLF 2 and Smad family member 7 (SMAD7 as the NGF mediated novel downstream genes in hematopoietic cells. Finally, the downregulation of KLF2 gene enhanced imatinib induced apoptosis. Conclusion NGF does not induce genes which are involved in immune related functions, but induces proliferation and survival signals in HMC-1(V560G c-Kit cells. Furthermore, the current data provide novel candidate genes, KLF2 and SMAD7 which are induced by NGF/TrkA activation in hematopoietic cells. Since the depletion of KLF2 causes enhanced apoptosis of HMC-1(V560G c-Kit, KLF2 may play a role in the NGF mediated survival signal.

Dittrich-Breiholz Oliver

2011-04-01

313

Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application.  

Science.gov (United States)

Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P state MSNA was decreased by 31% (P state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure. PMID:25128165

Harada, Daisuke; Asanoi, Hidetsugu; Takagawa, Junya; Ishise, Hisanari; Ueno, Hiroshi; Oda, Yoshitaka; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

2014-10-15

314

Two types of cochlear hair cells with two different modes of activation are better than one.  

Science.gov (United States)

The hair cells are the receptor cells of the inner ear. There is still controversy concerning the mechanism of their activation. Studies on the hair cells of the bullfrog sacculus have provided much information on the activity of hair cells. However, the mammalian cochlea has two different types of hair cells - the inner hair cells (IHCs) and the outer hair cells (OHCs) - and it is likely that their activation mechanisms are not identical. Mechanical manipulations of the cochlea and measurements of the passive and active displacements of the basilar membrane in the normal and postmortem cochleas provide evidence that the OHCs are activated directly by the fluid pressures induced in the cochlea by low-level sound, and not indirectly by a passive traveling wave. The activated OHCs produce active displacements (the cochlear amplifier) which excite the IHCs, probably by deflecting their stereocilia, followed by excitation of the auditory nerve fibers. PMID:22865443

Sohmer, Haim

2012-01-01

315

Activating transcription factor 3 (ATF3, a useful marker for regenerative response after nerve root injury  

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After sciatic nerve transection ATF3 immunoreactivity (ATF3 IR was detected in a few DRG neurons already 6 hours (h after the lesion. After 24h the number had clearly increased and still at 3 weeks DRG neurons remained labeled. In the ventral horn, ATF3 IR in motoneurons was first detected 24h after the sciatic nerve transection, and still 3 weeks postoperatively lesioned motoneurons showed ATF3 labeling. After a ventral root avulsion many spinal motoneurons showed ATF3 IR already after 3h, and after 6h all motoneurons were labeled. At 3 weeks a majority of the lesioned motoneurons had died, but all the remaining ones were labeled. When an avulsed ventral root was directly replanted, motoneurons survived and were still labeled at 5 weeks. In DRG, a few neurons were labeled already at 1,5h after a dorsal root avulsion. At 24h the number had increased but still only a minority of the neurons were labeled. At 3 days the number of labeled neurons was reduced, and a further reduction was at hand at 7 days and 3 weeks. In parallel, in humans, 3 days after a traumatic dorsal root avulsion, only a few DRG neurons showed ATF3 IR. At 6 weeks no labeled neurons could be detected. These facts imply that ATF3 response to axotomy involves a distance dependent mechanism. ATF3 also appears to be a useful and reliable neuronal marker of nerve lesions even in humans. In addition, ATF3 up-regulation in both motor and sensory neurons seems to be linked to regenerative competence.

HansLindå

2011-05-01

316

Differential gene expression in proximal and distal nerve segments of rats with sciatic nerve injury during Wallerian degeneration.  

Science.gov (United States)

Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves undergoing Wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identified, mainly between proximal and distal segments at 7-14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inflammatory response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were verified for four genes: aquaporin-4, interleukin 1 receptor-like 1, matrix metalloproteinase-12 and periaxin. Our study identifies differential gene expression in the proximal and distal segments of a nerve during Wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during Wallerian degeneration. PMID:25206781

Jiang, Nan; Li, Huaiqin; Sun, Yi; Yin, Dexin; Zhao, Qin; Cui, Shusen; Yao, Dengbing

2014-06-15

317

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

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

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

2009-11-15

318

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

International Nuclear Information System (INIS)

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

319

Plexiform hybrid granular cell tumor/perineurioma: a novel variant of benign peripheral nerve sheath tumor with divergent differentiation.  

Science.gov (United States)

The descriptive term hybrid peripheral nerve sheath tumor refers to any neoplasm of the neurilemmal apparatus composed of more than one pathologically defined tumoral equivalent derived from its constituent cells. Within this uncommon nosological category, participation of granular cell tumor - a neoplasm of modified Schwann cells - has been reported only exceptionally. We describe a hitherto not documented variant composed of an organoid mixture of granular cell tumor and perineurioma with plexiform growth. A solitary subcutaneous nodule of 1.5 cm diameter was excised from the right ring finger of a 19-year-old female with no antecedents of neurofibromatosis or relevant trauma. Histology revealed a monotonous, yet cytologically dimorphic proliferation of classical granular cells intermingled with flattened, inconspicuous perineurial cells. Immunohistochemical double labeling detected expression of S100 protein in the former and of EMA and GLUT-1 in the latter. While the respective staining patterns for S100 protein and EMA or GLUT-1 tended to be mutually exclusive, a minority of cells exhibited transitional granular cell/perineurial immunophenotype. Electron microscopy permitted direct visualization of a plethora of lysosomes in the granular cell moiety, and of pinocytotic vesicles and tight junctions in perineurial cells. Intratumoral axons were not detected. Expanding intraneurally, the lesion showed discrete encapsulation by the local perineurium, and resulted in plexiform growth. The MIB-1 labeling index averaged 1%. We interpret our findings as supporting evidence for the dual cell lineage to have arisen through metaplasia, with the tumor's dynamics probably having been driven by the granular cell component. PMID:22494537

Matter, Alexandra; Hewer, Ekkehard; Kappeler, Andreas; Fleischmann, Achim; Vajtai, Istvan

2012-05-15

320

Decreased Nerve Conduction Velocity in Football Players  

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

Daryoush Didehdar

2014-06-01

 
 
 
 
321

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

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

Zhen Li

2013-01-01

322

A mathematical model of long-term renal sympathetic nerve activity inhibition during an increase in sodium intake.  

Science.gov (United States)

It is well known that renal nerves directly affect renal vascular resistance, tubular sodium reabsorption, and renin secretion. Inhibition of renal sympathetic nerve activity (RSNA) decreases renal vascular resistance, tubular sodium reabsorption, and renin secretion, leading to an increase in sodium excretion. Although several studies show that inhibition of RSNA promotes sodium excretion during an acute blood volume expansion, there is limited research relating to the importance of RSNA inhibition that contributes to sodium homeostasis during a long-term increase in sodium intake. Therefore, to dissect the underlying mechanisms of sodium excretion, a mathematical model of a cardiovascular system consisting of two kidneys, each with an independent RSNA, was developed. Simulations were performed to determine the responses of RSNA and sodium excretion to an increased sodium intake. In these simulations, RSNA in the left kidney was fixed at its normal steady-state value, while RSNA in the contralateral kidney was allowed to change normally in response to the increased sodium intake. The results demonstrate that the fixed-RSNA kidney excretes less sodium than the intact-RSNA collateral kidney. Because each kidney is exposed to the same arterial pressure and circulatory hormones, the impaired sodium excretion in the absence of RSNA inhibition supports the hypothesis that RSNA inhibition contributes to natriuresis in response to a long-term increase in sodium intake. PMID:24285363

Karaaslan, Fatih; Denizhan, Yagmur; Hester, Robert

2014-02-15

323

Variable functional recovery and minor cell loss in the ganglion cell layer of the lizard Gallotia galloti after optic nerve axotomy.  

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The lizard Gallotia galloti shows spontaneous and slow axon regrowth through a permissive glial scar after optic nerve axotomy. Although much of the expression pattern of glial, neuronal and extracellular matrix markers have been analyzed by our group, an estimation of the cell loss in the ganglion cell layer (GCL) and the degree of visual function recovery remained unresolved. Thus, we performed a series of tests indicative of effective visual function (pupillary light reflex, accommodation, visually elicited behavior) in 18 lizards at 3, 6, 9 and 12 months post-axotomy which were then processed for immunohistochemistry for the neuronal markers SMI-31 (neurofilaments), Tuj1 (beta-III tubulin) and SV2 (synaptic vesicles) at the last timepoint. Separately, cell loss in the GCL was estimated by comparative quantitation of DAPI(+) nuclei in control and 12 months experimental lizards. Additionally, 15 lizards were processed for electron microscopy to monitor relevant ultrastructural changes in the GCL, optic nerve and optic tract throughout regeneration. Hypertrophy of RGCs was persistent, morphology of the regenerated nerves varied from narrow to neuroma-like features and larger regenerated axons underwent remyelination by 9 months. The estimated cell loss in the GCL was 27% and two-third of the animals recovered the pupillary light reflex which involves the pretectum. Strikingly, visually elicited behavior involving the tectum was only restored in two specimens, presumably due to the higher complexity of this pathway. These preliminary results indicate that limited functional regeneration occurs spontaneously in the severely injured visual system of the lacertid G. galloti. PMID:24184031

Santos, E; Romero-Alemán, M M; Monzón-Mayor, M; Yanes, C

2014-01-01

324

Near nerve potencial of sural nerve in leprosy  

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Full Text Available Leprosy neuropathy is characterized by initial involvement of the small nerve fibers, later followed by involvement of the large fibers, when routine nerve conduction studies become abnormal. To increase the diagnostic yield and precocity of these studies, we applied the near nerve technique to the sural nerve of 8 leprosy patients. Contrary to our expectations, the main component of the sural nerve sensory action potential was abnormal in all patients, but the minimum conduction velocity originating from small 3-6 mm fibers was normal or only mildly involved in three patients. Also, although Schwann cells are the first to be involved in leprosy, the results are suggestive of axonal degeneration instead of demyelination. To better understand the neurophysiology and physiology of leprosy and to increase the accuracy and precocity of the diagnosis, it will be necessary to investigate patients in the very early stages of the disease and to correlate these findings with the corresponding nerve pathology.

Arruda Ana Paula M.

2004-01-01

325

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

LENUS (Irish Health Repository)

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

Costello, Richard W

2011-05-01

326

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

LENUS (Irish Health Repository)

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

Costello, Richard W

2012-02-01

327

Alpha-Synuclein Oligomerization in Manganese-Induced Nerve Cell Injury in Brain Slices: A Role of NO-Mediated S-Nitrosylation of Protein Disulfide Isomerase.  

Science.gov (United States)

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

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

2014-12-01

328

SP-100 reactor cell activation  

International Nuclear Information System (INIS)

There are plans to test the SP-100 space reactor for 2 yr in the test facility shown in Figure 1. The vacuum vessel will be in the reactor experiment (RX) cell surrounded by an inert gas atmosphere. It is proposed that the reactor test cell could contain removable-water- shielding tanks to reduce the residual activation dose rates in the test cell after the tests are completed. This reduction will allow the facility to be considered for other uses after the SP-100 tests are completed. The radiation dose rates in the test cell were calculated for several configurations of water-shielding tanks to help evaluate this concept

329

Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation.  

Science.gov (United States)

The pigment cells of vertebrates serve a variety of functions and generate a stunning variety of patterns. These cells are also implicated in human pathologies including melanoma. Whereas the events of pigment cell development have been studied extensively in the embryo, much less is known about morphogenesis and differentiation of these cells during post-embryonic stages. Previous studies of zebrafish revealed genetically distinct populations of embryonic and adult melanophores, the ectotherm homologue of amniote melanocytes. Here, we use molecular markers, vital labeling, time-lapse imaging, mutational analyses, and transgenesis to identify peripheral nerves as a niche for precursors to adult melanophores that subsequently migrate to the skin to form the adult pigment pattern. We further identify genetic requirements for establishing, maintaining, and recruiting precursors to the adult melanophore lineage and demonstrate novel compensatory behaviors during pattern regulation in mutant backgrounds. Finally, we show that distinct populations of latent precursors having differential regenerative capabilities persist into the adult. These findings provide a foundation for future studies of post-embryonic pigment cell precursors in development, evolution, and neoplasia. PMID:21625562

Budi, Erine H; Patterson, Larissa B; Parichy, David M

2011-05-01

330

Rac1 Selective Activation Improves Retina Ganglion Cell Survival and Regeneration  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs) do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role ...

Lorenzetto, Erika; Ettorre, Michele; Pontelli, Valeria; Bolomini-vittori, Matteo; Bolognin, Silvia; Zorzan, Simone; Laudanna, Carlo; Buffelli, Mario

2013-01-01

331

The effect of orally administered glycogen on anti-tumor activity and natural killer cell activity in mice.  

Science.gov (United States)

Natural killer (NK) cells, innate immune effectors that mediate rapid responses to various antigens, play an important role in potentiating host defenses through the clearance of tumor cells and virally infected cells. By using enzymatically synthesized glycogen (ESG) with the same characteristics as natural glycogen, we examined whether orally administered glycogen enhances the innate defense of tumor-implanted mice and the cytotoxicity of NK cells. Oral administration of ESG led to the suppression of tumor proliferation and the prolongation of survival times of tumor-bearing mice. Splenic NK activities of BALB/c mice treated orally with ESG were significantly higher than those of water-treated mice, which were used as a negative control. In addition, intraduodenal injections of ESG gradually and markedly lowered splenic sympathetic nerve activity, which has an inverse correlation with NK activity. Furthermore, ESG activated Peyer's patch cells to induce the production of macrophage inflammatory protein-2 (MIP-2), interleukin-6 (IL-6), and immunoglobulin A (IgA) from these cells. These results demonstrated that orally administrated glycogen significantly enhanced the cytotoxicity of NK cells by acting on Peyer's patch cells and autonomic nerves, and eventually induced the potentiation of host defenses. We propose that glycogen functions not only as an energy source for life support but also as an oral adjuvant for immunopotentiation. PMID:22080051

Kakutani, Ryo; Adachi, Yoshiyuki; Kajiura, Hideki; Takata, Hiroki; Kuriki, Takashi; Ohno, Naohito

2012-01-01

332

Analysis of structural and molecular events associated with adult rat optic chiasm and nerves demyelination and remyelination: possible role for 3rd ventricle proliferating cells.  

Science.gov (United States)

Multiple sclerosis frequently affects the optic apparatus, particularly optic chiasm and nerves. Here, we have reported the structural and molecular characteristics of remyelination in the adult rat optic chiasm and nerves. Moreover, considering the proximity of optic chiasm and 3rd ventricle, we have tried to determine if proliferating cells residing in 3rd ventricle region are able to migrate in response to experimental demyelination of the optic chiasm. Following local demyelination by lysolecithin, remyelination pattern in longitude of optic chiasm and proximal nerves was investigated using myelin staining and marker genes expression. Furthermore, cell tracing was carried out using BrdU labeling of proliferating cells prior to gliotoxin injection. Morphometric analysis revealed that demyelination was considerable on days 7 and 14 and an incomplete remyelination occurred on day 28 post-lesion. Interestingly, myelin repair was more evident in the caudal part of chiasm, compared to rostral part and proximal optic nerves. Following chiasm and nerve demyelination, trains of BrdU+ cells were seen near the 3rd ventricle which subsequently moved to lesion site. Nestin was significantly up-regulated in 3rd ventricle surroundings. At the lesion site, Nogo-A gene expression was significantly decreased on days 7 and 14 post lesion, while Olig2, nestin, and GFAP expression was increased on day 7. The changes were then reversed by the time. Myelin repair in optic chiasm seems to be mediated by endogenous progenitors and stem cells. Adult 3rd ventricle proliferating cells may play a role in this context by mobilization into the demyelinated chiasm. PMID:21290199

Mozafari, Sabah; Javan, Mohammad; Sherafat, Mohammad Amin; Mirnajafi-Zadeh, Javad; Heibatollahi, Motahareh; Pour-Beiranvand, Shahram; Tiraihi, Taki; Ahmadiani, Abolhasan

2011-06-01

333

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

Science.gov (United States)

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 processes. In contrast, NGF did not support survival above control levels (30%) and induced neurite formation from approximately one-third of the surviving cells. C6-CM and NGF had no additive effects on neurite outgrowth. C6-CM-mediated fiber outgrowth was not inhibited by physiological concentrations of glucocorticoids which abolished the NGF-induced neurite formation. Both C6-CM and NGF increased the catecholamine content of the cultures and reduced the relative content of epinephrine. However, in view of its substantial effect on cell survival as compared to NGF, C6-CM caused a reduction of the catecholamine content per cell. We conclude that adrenal medullary cells, like other members of the sensory-sympathetic cell lineage of the neural crest, respond to glial-conditioned medium. This response differs both quantitatively and qualitatively from that mediated by NGF. Images PMID:6371811

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

1984-01-01

334

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

DEFF Research Database (Denmark)

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

Fjord-Larsen, Lone; Kusk, Philip

2010-01-01

335

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

International Nuclear Information System (INIS)

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

336

Abnormal neutrophil chemotactic activity in children with congenital insensitivity to pain with anhidrosis (CIPA): the role of nerve growth factor.  

Science.gov (United States)

A 1926-ins-T mutation in the TrkA gene encoding the tyrosine kinase receptor for nerve growth factor (NGF) was previously documented in patients with congenital insensitivity to pain with anhidrosis (CIPA). These patients suffer from skin lacerations which often evolve into deep tissue infections. Abnormality in neutrophil functions may explain this high rate of severe infections. In this study we show that chemotaxis was significantly (P<0.001) suppressed in patients' neutrophils, compared to healthy controls. Although NGF alone did not exert a chemotactic effect, its presence enhanced both migration toward fMLP and phosphorylation of MAP kinases (ERK and JNK) in neutrophils from healthy controls, but not in neutrophils from CIPA patients. The significantly impaired chemotactic activity of neutrophils from a CIPA patient, which has been attributed to the molecular defect in the TrkA receptor, may contribute to the high rate of infection. PMID:18955016

Beigelman, Avraham; Levy, Jacov; Hadad, Nurit; Pinsk, Vered; Haim, Alon; Fruchtman, Yariv; Levy, Rachel

2009-03-01

337

Transcutaneous electrical nerve stimulation (TENS) improves upper GI symptoms and balances the sympathovagal activity in scleroderma patients.  

Science.gov (United States)

To assess the impact of transcutaneous electrical nerve stimulation (TENS) at gastrointestinal (GI) acupoints on GI symptoms and quality of life in scleroderma patients, 17 patients filled out SF-36 and GI symptom questionnaires before the electrocardiogram was recorded for two intervals: baseline and TENS. At home, patients applied TENS for 14 days, then were reassessed. Acutely, TENS application significantly increased sympathetic and vagal activities vs. baseline (P=0.02 and P=0.004), respectively. Prolonged TENS application normalized the sympathovagal balance (P=0.04), decreased GI symptom scores (P=0.02) and increased the physical functioning score (SF36), which strongly correlated with the change in the sympathovagal balance (r=0.6, P=0.02). In conclusion, TENS at GI acupoints offers a potential option in the treatment of upper GI symptoms, but further study is necessary. PMID:17372833

Sallam, Hanaa; McNearney, Terry A; Doshi, Dipti; Chen, J D Z

2007-05-01

338

Selective expression of Narp in primary nociceptive neurons: Role in microglia/macrophage activation following nerve injury.  

Science.gov (United States)

Neuronal activity regulated pentraxin (Narp) is a secreted protein implicated in regulating synaptic plasticity via its association with the extracellular surface of AMPA receptors. We found robust Narp immunostaining in dorsal root ganglia (DRG) that is largely restricted to small diameter neurons, and in the superficial layers of the dorsal horn of the spinal cord. In double staining studies of DRG, we found that Narp is expressed in both IB4- and CGRP-positive neurons, markers of distinct populations of nociceptive neurons. Although a panel of standard pain behavioral assays were unaffected by Narp deletion, we found that Narp knockout mice displayed an exaggerated microglia/macrophage response in the dorsal horn of the spinal cord to sciatic nerve transection 3days after surgery compared with wild type mice. As other members of the pentraxin family have been implicated in regulating innate immunity, these findings suggest that Narp, and perhaps other neuronal pentraxins, also regulate inflammation in the nervous system. PMID:25005116

Miskimon, M; Han, S; Lee, J J; Ringkamp, M; Wilson, M A; Petralia, R S; Dong, X; Worley, P F; Baraban, J M; Reti, I M

2014-09-15

339

c-Jun activation in Schwann cells protects against loss of sensory axons in inherited neuropathy.  

Science.gov (United States)

Charcot-Marie-Tooth disease type 1A is the most frequent inherited peripheral neuropathy. It is generally due to heterozygous inheritance of a partial chromosomal duplication resulting in over-expression of PMP22. A key feature of Charcot-Marie-Tooth disease type 1A is secondary death of axons. Prevention of axonal loss is therefore an important target of clinical intervention. We have previously identified a signalling mechanism that promotes axon survival and prevents neuron death in mechanically injured peripheral nerves. This work suggested that Schwann cells respond to injury by activating/enhancing trophic support for axons through a mechanism that depends on upregulation of the transcription factor c-Jun in Schwann cells, resulting in the sparing of axons that would otherwise die. As c-Jun orchestrates Schwann cell support for distressed neurons after mechanical injury, we have now asked: do Schwann cells also activate a c-Jun dependent neuron-supportive programme in inherited demyelinating disease? We tested this by using the C3 mouse model of Charcot-Marie-Tooth disease type 1A. In line with our previous findings in humans with Charcot-Marie-Tooth disease type 1A, we found that Schwann cell c-Jun was elevated in (uninjured) nerves of C3 mice. We determined the impact of this c-Jun activation by comparing C3 mice with double mutant mice, namely C3 mice in which c-Jun had been conditionally inactivated in Schwann cells (C3/Schwann cell-c-Jun(-/-) mice), using sensory-motor tests and electrophysiological measurements, and by counting axons in proximal and distal nerves. The results indicate that c-Jun elevation in the Schwann cells of C3 nerves serves to prevent loss of myelinated sensory axons, particularly in distal nerves, improve behavioural symptoms, and preserve F-wave persistence. This suggests that Schwann cells have two contrasting functions in Charcot-Marie-Tooth disease type 1A: on the one hand they are the genetic source of the disease, on the other, they respond to it by mounting a c-Jun-dependent response that significantly reduces its impact. Because axonal death is a central feature of much nerve pathology it will be important to establish whether an axon-supportive Schwann cell response also takes place in other conditions. Amplification of this axon-supportive mechanism constitutes a novel target for clinical intervention that might be useful in Charcot-Marie-Tooth disease type 1A and other neuropathies that involve axon loss. PMID:25216747

Hantke, Janina; Carty, Lucy; Wagstaff, Laura J; Turmaine, Mark; Wilton, Daniel K; Quintes, Susanne; Koltzenburg, Martin; Baas, Frank; Mirsky, Rhona; Jessen, Kristján R

2014-11-01

340

Accuracy of regenerating motor neurons: influence of diffusion in denervated nerve.  

Science.gov (United States)

Following injury to a peripheral nerve the denervated distal nerve segment undergoes remarkable changes including loss of the blood-nerve barrier, Schwann cell proliferation, macrophage invasion, and the production of many cytokines and neurotrophic factors. The aggregate consequence of such changes is that the denervated nerve becomes a permissive and even preferred target for regenerating axons from the proximal nerve segment. The possible role that an original end-organ target (e.g. muscle) may play in this phenomenon during the regeneration period is largely unexplored. We used the rat femoral nerve as an in vivo model to begin to address this question. We also examined the effects of disrupting communication with muscle in terms of accuracy of regenerating motor neurons as judged by their ability to correctly project to their original terminal nerve branch. Our results demonstrate that the accuracy of regenerating motor neurons is dependent upon the denervated nerve segment remaining in uninterrupted continuity with muscle. We hypothesized that this influence of muscle on the denervated nerve might be via diffusion-driven movement of biomolecules or the active axonal transport that continues in severed axons for several days in the rat, so we devised experiments to separate these two possibilities. Our data show that disrupting ongoing diffusion-driven movement in a denervated nerve significantly reduces the accuracy of regenerating motor neurons. PMID:24846614

Madison, R D; Robinson, G A

2014-07-25

 
 
 
 
341

Vestibular modulation of muscle sympathetic nerve activity by the utricle during sub-perceptual sinusoidal linear acceleration in humans.  

Science.gov (United States)

We assessed the capacity for the vestibular utricle to modulate muscle sympathetic nerve activity (MSNA) during sinusoidal linear acceleration at amplitudes extending from imperceptible to clearly perceptible. Subjects (n = 16) were seated in a sealed room, eliminating visual cues, mounted on a linear motor that could deliver peak sinusoidal accelerations of 30 mG in the antero-posterior direction. Subjects sat on a padded chair with their neck and head supported vertically, thereby minimizing somatosensory cues, facing the direction of motion in the anterior direction. Each block of sinusoidal motion was applied at a time unknown to subjects and in a random order of amplitudes (1.25, 2.5, 5, 10, 20 and 30 mG), at a constant frequency of 0.2 Hz. MSNA was recorded via tungsten microelectrodes inserted into muscle fascicles of the common peroneal nerve. Subjects used a linear potentiometer aligned to the axis of motion to indicate any perceived movement, which was compared with the accelerometer signal of actual room movement. On average, 67% correct detection of movement did not occur until 6.5 mG, with correct knowledge of the direction of movement at ~10 mG. Cross-correlation analysis revealed potent sinusoidal modulation of MSNA even at accelerations subjects could not perceive (1.25-5 mG). The modulation index showed a positive linear increase with acceleration amplitude, such that the modulation was significantly higher (25.3 ± 3.7%) at 30 mG than at 1.25 mG (15.5 ± 1.2%). We conclude that selective activation of the vestibular utricle causes a pronounced modulation of MSNA, even at levels well below perceptual threshold, and provides further evidence in support of the importance of vestibulosympathetic reflexes in human cardiovascular control. PMID:24504198

Hammam, Elie; Hau, Chui Luen Vera; Wong, Kwok-Shing; Kwok, Kenny; Macefield, Vaughan G

2014-04-01

342

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

Directory of Open Access Journals (Sweden)

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

Chrzaszcz MaryAnn

2010-05-01

343

Inhibition of protein kinase C restores Na+,K(+)-ATPase activity in sciatic nerve of diabetic mice.  

Science.gov (United States)

We have tested if inhibition of protein kinase C is able to prevent and/or to restore the decrease of Na+,K(+)-ATPase activity in the sciatic nerve of alloxan-induced diabetic mice. Mice were made diabetic by subcutaneous injection of 200 mg of alloxan/kg of body weight. The activity of Na+,K(+)-ATPase decreased rapidly (43% after 3 days) and slightly thereafter (58% at 11 days). We show that intraperitoneal injection of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C, prevents completely the loss of Na+,K(+)-ATPase activity produced by alloxan. Also, H7 injected into diabetic mice, 4-9 days after the injection of alloxan, restores the activity of the enzyme. The amount of activity recovered depends on the dose of H7 administered; complete recovery was reached with injection of 15 mg of H7/kg of body weight. The effect of H7 is transient, with a half-life of approximately 1 h. PMID:1312572

Hermenegildo, C; Felipo, V; Miñana, M D; Grisolía, S

1992-04-01

344

Nerve growth factor and neurotrophin-3 mediate survival of pulmonary plasma cells during the allergic airway inflammation.  

Science.gov (United States)

Allergen-specific Abs play a pivotal role in the induction and maintenance of allergic airway inflammation. During secondary immune responses, plasma cell survival and Ab production is mediated by extrinsic factors provided by the local environment (survival niches). It is unknown whether neurotrophins, a characteristic marker of allergic airway inflammation, influence plasma cell survival in the lung. Using a mouse model of allergic asthma, we found that plasma cells from the lung and spleen are distinct subpopulations exhibiting differential expression patterns of neurotrophins and their receptors (Trks). In vitro, the nerve growth factor (NGF) and neurotrophin-3