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Sample records for nerve growth factor-sensitive

  1. Nerve growth factor and asthma.

    PubMed

    Bonini, S; Lambiase, A; Lapucci, G; Properzi, F; Bresciani, M; Bracci Laudiero, M L; Mancini, M J; Procoli, A; Micera, A; Sacerdoti, G; Bonini, S; Levi-Schaffer, F; Rasi, G; Aloe, L

    2002-01-01

    An increasing body of evidence shows that nerve growth factor (NGF) exerts biological activity not only on the central and peripheral nervous system, but also on the immune system thereby influencing allergic diseases and asthma. (1) NGF circulating levels are increased in patients with allergic diseases and asthma, and are related to the severity of the inflammatory process and disease. In vernal keratoconjunctivitis, NGF plasma levels correlate with the number of mast cells infiltrating the conjunctiva, and NGF mRNA is increased in nasal mucosal scrapings of patients with allergic rhinitis who have high levels of NGF in serum and nasal fluids; NGF is further increased in nasal fluids after specific allergen challenge. (2) NGF is produced and released by several modulatory and effector cells of allergic inflammation and asthma, for example T-helper 2 lymphocytes, mast cells and eosinophils. (3) NGF receptors are expressed on the conjunctival epithelium of patients with allergic conjunctivitis and the number of NGF-receptor positive cells is increased in the conjunctiva of these patients. Indeed, local administration of NGF induces fibroblast activation and healing processes of human corneal ulcers, which suggests that NGF plays a role in tissue remodelling processes occurring in asthma. (4) NGF increases airway hyperreactivity to histamine in an animal model of asthma, while anti-NGF treatment reduces airway hyperreactivity induced by ovalbumin topical challenge in the sensitized mouse. PMID:12144547

  2. Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

    PubMed Central

    Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

    2013-01-01

    Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

  3. Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects.

    PubMed

    Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

    2013-11-25

    Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

  4. Hepatocyte growth factor sensitizes brain tumors to c-MET kinase inhibition

    PubMed Central

    Zhang, Ying; Farenholtz, Kaitlyn E.; Yang, Yanzhi; Guessous, Fadila; diPierro, Charles G.; Calvert, Valerie S.; Deng, Jianghong; Schiff, David; Xin, Wenjun; Lee, Jae K.; Purow, Benjamin; Christensen, James; Petricoin, Emanuel; Abounader, Roger

    2013-01-01

    Purpose The receptor tyrosine kinase (RTK) c-MET and its ligand hepatocyte growth factor (HGF) are deregulated and promote malignancy in cancer and brain tumors. Consequently, clinically applicable c-MET inhibitors have been developed. The purpose of this study was to investigate the not well known molecular determinants that predict responsiveness to c-MET inhibitors, and to explore new strategies for improving inhibitor efficacy in brain tumors. Experimental design We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells (GSCs), and established cell line-derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done. We also explored new approaches for improving the efficacy of the inhibitors in vitro and in vivo. Results We found that HGF co-expression is a key predictor of response to c-MET inhibition among the examined factors, and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET inhibition in responsive and non-responsive cells. Surprisingly, we also found that short pre-treatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the anti-tumor effects of c-MET inhibition. We observed a similar ligand-induced sensitization effect to an EGFR small molecule kinase inhibitor. Conclusions These findings allow the identification of a subset of patients that will be responsive to c-MET inhibition, and propose ligand pre-treatment as a potential new strategy for improving the anti-cancer efficacy of RTK inhibitors. PMID:23386689

  5. Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth

    NASA Astrophysics Data System (ADS)

    Lin, Keng-Min; Shea, Jill; Gale, Bruce K.; Sant, Himanshu; Larrabee, Patti; Agarwal, Jay

    2016-04-01

    Nerve injury can occur due to penetrating wounds, compression, traumatic stretch, and cold exposure. Despite prompt repair, outcomes are dismal. In an attempt to help resolve this challenge, in this work, a poly-lactic-co-glycolic acid (PLGA) nerve conduit with associated biodegradable drug reservoir was designed, fabricated, and tested. Unlike current nerve conduits, this device is capable of fitting various clinical scenarios by delivering different drugs without reengineering the whole system. To demonstrate the potential of this device for nerve repair, a series of experiments were performed using nerve growth factor (NGF). First, an NGF dosage curve was developed to determine the minimum NGF concentration for optimal axonal outgrowth on chick dorsal root ganglia (DRG) cells. Next, PLGA devices loaded with NGF were evaluated for sustained drug release and axon growth enhancement with the released drug. A 20 d in vitro release test was conducted and the nerve conduit showed the ability to meet and maintain the minimum NGF requirement determined previously. Bioactivity assays of the released NGF showed that drug released from the device between the 15th and 20th day could still promote axon growth (76.6-95.7 μm) in chick DRG cells, which is in the range of maximum growth. These novel drug delivery conduits show the ability to deliver NGF at a dosage that efficiently promotes ex vivo axon growth and have the potential for in vivo application to help bridge peripheral nerve gaps.

  6. Nerve Growth Factor and Diabetic Neuropathy

    PubMed Central

    Vinik, Aaron

    2003-01-01

    Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50–90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal abnormalities in diabetes can be duplicated by experimental depletion of specific neurotrophic factors, their receptors or their binding proteins. In experimental models of diabetes there is a reduction in the availability of these growth factors, which may be a consequence of metabolic abnormalities, or may be independent of glycemic control. These neurotrophic factors are required for the maintenance of the neurons, the ability to resist apoptosis and regenerative capacity. The best studied of the neurotrophic factors is nerve growth factor (NGF) and the related members of the neurotrophin family of peptides. There is increasing evidence that there is a deficiency of NGF in diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) that may also contribute to the clinical symptoms resulting from small fiber dysfunction. Similarly, NT3 appears to be important for large fiber and IGFs for autonomic neuropathy. Whether the observed growth factor deficiencies are due to decreased synthesis, or functional, e.g. an inability to bind to their receptor, and/or abnormalities in nerve transport and processing, remains to be established. Although early studies in humans on the role of neurotrophic factors as a therapy for diabetic neuropathy have been unsuccessful, newer agents and the possibilities uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate that neurotrophic factor therapy, specifically targeted at different nerve fiber populations, might enter the therapeutic armamentarium. PMID:14668049

  7. Let-7 microRNAs Regenerate Peripheral Nerve Regeneration by Targeting Nerve Growth Factor

    PubMed Central

    Li, Shiying; Wang, Xinghui; Gu, Yun; Chen, Chu; Wang, Yaxian; Liu, Jie; Hu, Wen; Yu, Bin; Wang, Yongjun; Ding, Fei; Liu, Yan; Gu, Xiaosong

    2015-01-01

    Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF) promotes peripheral nerve regeneration, but its clinical applications are limited by several constraints. In this study, we found that the time-dependent expression profiles of eight let-7 family members in the injured nerve after sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs) significantly reduced cell proliferation and migration of primary Schwann cells (SCs) by directly targeting NGF and suppressing its protein translation. Following sciatic nerve injury, the temporal change in let-7 miRNA expression was negatively correlated with that in NGF expression. Inhibition of let-7 miRNAs increased NGF secretion by primary cultured SCs and enhanced axonal outgrowth from a coculture of primary SCs and dorsal root gangalion neurons. In vivo tests indicated that let-7 inhibition promoted SCs migration and axon outgrowth within a regenerative microenvironment. In addition, the inhibitory effect of let-7 miRNAs on SCs apoptosis might serve as an early stress response to nerve injury, but this effect seemed to be not mediated through a NGF-dependent pathway. Collectively, our results provide a new insight into let-7 miRNA regulation of peripheral nerve regeneration and suggest a potential therapy for repair of peripheral nerve injury. PMID:25394845

  8. Comparison of divided sciatic nerve growth within dermis, venous and nerve graft conduit in rat

    PubMed Central

    Fatemi, Mohammad Javad; Foroutan, Kamal Seyed; Ashtiani, Abass Kazemi; Mansoori, Maryam Jafari; Vaghardoost, Reza; Pedram, Sepehr; Hosseinpolli, Aidin; Rajabi, Fatemeh; Mousavi, Seyed Jaber

    2010-01-01

    BACKGROUND: Considering the common origin of skin and peripheral nervous system, a tube of dermal layer of skin hypothetically can be an ideal conduit for nerve reconstruction. An experimental study performed to evaluate the nerve regeneration of efficacy into a dermal tube. METHODS: Sixty male Wistar rats were used. A 10 mm gap was produced in right sciatic nerves. In group A the autogenous nerve grafts were used to bridge the defects. In group B vein conduit were use to reconstruct the gaps. In group C dermal tube were used to bridge the defects. Morphologic studies were carried out after 3 month. RESULTS: The density of nerve fibers was significantly higher in autogenous nerve graft group. The efficacy of nerve growth into the dermal tube group was significantly poor in comparison to other groups. CONCLUSIONS: In the present study, dermis was used as the nerve conduit for the first time. This study indicates that the dermal tube is not a suitable conduit for nerve regeneration till further studies to resolve the problems before clinical application. PMID:21526083

  9. Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs

    PubMed Central

    Hedlund, Eva-Maria Eleonora; Yang, Xiaojuan; Zhang, Yin; Yang, Yunlong; Shibuya, Masabumi; Zhong, Weide; Sun, Baocun; Liu, Yizhi; Hosaka, Kayoko; Cao, Yihai

    2013-01-01

    The role of placental growth factor (PlGF) in modulation of tumor angiogenesis and tumor growth remains an enigma. Furthermore, anti-PlGF therapy in tumor angiogenesis and tumor growth remains controversial in preclinical tumor models. Here we show that in both human and mouse tumors, PlGF induced the formation of dilated and normalized vascular networks that were hypersensitive to anti-VEGF and anti–VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using plgf shRNA in a human choriocarcinoma significantly accelerated tumor growth rates and acquired resistance to anti-VEGF drugs, whereas gain-of-function of PlGF in a mouse tumor increased anti-VEGF sensitivity. Further, we show that VEGFR-2 and VEGFR-1 blocking antibodies displayed opposing effects on tumor angiogenesis. VEGFR-1 blockade and genetic deletion of the tyrosine kinase domain of VEGFR-1 resulted in enhanced tumor angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and tumor growth and may potentially serve as a predictive marker of anti-VEGF cancer therapy. PMID:23267058

  10. A photon-driven micromotor can direct nerve fibre growth

    NASA Astrophysics Data System (ADS)

    Wu, Tao; Nieminen, Timo A.; Mohanty, Samarendra; Miotke, Jill; Meyer, Ronald L.; Rubinsztein-Dunlop, Halina; Berns, Michael W.

    2012-01-01

    Axonal path-finding is important in the development of the nervous system, nerve repair and nerve regeneration. The behaviour of the growth cone at the tip of the growing axon determines the direction of axonal growth and migration. We have developed an optical-based system to control the direction of growth of individual axons (nerve fibres) using laser-driven spinning birefringent spheres. One or two optical traps position birefringent beads adjacent to growth cones of cultured goldfish retinal ganglion cell axons. Circularly polarized light with angular momentum causes the trapped bead to spin. This creates a localized microfluidic flow generating an estimated 0.17 pN shear force against the growth cone that turns in response to the shear. The direction of axonal growth can be precisely manipulated by changing the rotation direction and position of this optically driven micromotor. A physical model estimating the shear force density on the axon is described.

  11. Identification and characterization of a cytoskeleton-associated, epidermal growth factor sensitive pp60c-src substrate.

    PubMed

    Maa, M C; Wilson, L K; Moyers, J S; Vines, R R; Parsons, J T; Parsons, S J

    1992-12-01

    In studies aimed at identifying and characterizing pp60c-src substrates that participate in the enhanced mitogenic response to epidermal growth factor (EGF) observed in murine C3H10T1/2 fibroblasts overexpressing c-src, we have identified a 75-kDa protein (p75) whose properties are consistent with those expected of such a substrate. We present evidence to show that p75 is immunologically related to a recently described, cytoskeleton-associated, pp60v-src substrate [Wu et al. (1991). Mol. Cell. Biol., 11, 5113-5124), and that its phosphotyrosine content is increased cooperatively by c-src overexpression and EGF stimulation. p75 is rapidly (within 2 min) phosphorylated on tyrosine upon EGF treatment and undergoes a second, prolonged phase of tyrosyl phosphorylation from 7 to 21 h after EGF addition, suggesting that tyrosyl phosphorylation of p75 is important for late as well as early events following EGF receptor activation. Enhanced tyrosyl phosphorylation of p75 is also seen when cells overexpressing c-src are treated with platelet-derived growth factor (PDGF), but significantly less phosphorylation is observed with insulin and fibroblast growth factor (FGF). Both basal and EGF-induced tyrosyl phosphorylation of p75 are reduced in cells overexpressing mutated forms of c-src (unmyristylated, or kinase deficient) as compared with wild-type c-src overexpressers, indicating the dependence of the enhanced tyrosyl phosphorylation on membrane-associated, enzymatically active pp60c-src. In cellular fractionation experiments p75 partitions with the cytosol, while immunofluorescence studies reveal a striking colocalization with pp60c-src at the plasma membrane and in the perinuclear region. Partial co-staining of p75 and actin occurs at the cell's periphery. These data provide evidence for p75 being a direct substrate of pp60c-src. The possible role of p75 in the enhanced response to EGF seen in c-src overexpressers is discussed. PMID:1281304

  12. Facilitation of facial nerve regeneration using chitosan-β-glycerophosphate-nerve growth factor hydrogel.

    PubMed

    Chao, Xiuhua; Xu, Lei; Li, Jianfeng; Han, Yuechen; Li, Xiaofei; Mao, YanYan; Shang, Haiqiong; Fan, Zhaomin; Wang, Haibo

    2016-06-01

    Conclusion C/GP hydrogel was demonstrated to be an ideal drug delivery vehicle and scaffold in the vein conduit. Combined use autologous vein and NGF continuously delivered by C/GP-NGF hydrogel can improve the recovery of facial nerve defects. Objective This study investigated the effects of chitosan-β-glycerophosphate-nerve growth factor (C/GP-NGF) hydrogel combined with autologous vein conduit on the recovery of damaged facial nerve in a rat model. Methods A 5 mm gap in the buccal branch of a rat facial nerve was reconstructed with an autologous vein. Next, C/GP-NGF hydrogel was injected into the vein conduit. In negative control groups, NGF solution or phosphate-buffered saline (PBS) was injected into the vein conduits, respectively. Autologous implantation was used as a positive control group. Vibrissae movement, electrophysiological assessment, and morphological analysis of regenerated nerves were performed to assess nerve regeneration. Results NGF continuously released from C/GP-NGF hydrogel in vitro. The recovery rate of vibrissae movement and the compound muscle action potentials of regenerated facial nerve in the C/GP-NGF group were similar to those in the Auto group, and significantly better than those in the NGF group. Furthermore, larger regenerated axons and thicker myelin sheaths were obtained in the C/GP-NGF group than those in the NGF group. PMID:26881479

  13. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury.

    PubMed

    Li, Hong-Fei; Wang, Yi-Ru; Huo, Hui-Ping; Wang, Yue-Xiang; Tang, Jie

    2015-11-01

    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration. PMID:26807123

  14. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

    PubMed Central

    Li, Hong-fei; Wang, Yi-ru; Huo, Hui-ping; Wang, Yue-xiang; Tang, Jie

    2015-01-01

    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration. PMID:26807123

  15. Nerve growth factor levels and localisation in human asthmatic bronchi.

    PubMed

    Olgart Höglund, C; de Blay, F; Oster, J P; Duvernelle, C; Kassel, O; Pauli, G; Frossard, N

    2002-11-01

    Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa. BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections. The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects. This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo, and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from

  16. Nerve growth factor binding domain of the nerve growth factor receptor

    SciTech Connect

    Welcher, A.A.; Bitler, C.M.; Radeke, M.J.; Shooter, E.M. )

    1991-01-01

    A structural analysis of the rat low-affinity nerve growth factor (NGF) receptor was undertaken to define the NGF binding domain. Mutant NGF receptor DNA constructs were expressed in mouse fibroblasts or COS cells, and the ability of the mutant receptors to bind NGF was assayed. In the first mutant, all but 16 amino acid residues of the intracellular domain of the receptor were removed. This receptor bound NGF with a K{sub d} comparable to that of the wild-type receptor. A second mutant contained only the four cysteine-rich sequences from the extracellular portion of the protein. This mutant was expressed in COS cells and the resultant protein was a secreted soluble form of the receptor that was able to bind NGF. Two N-terminal deletions, in which either the first cystein-rich sequence or the first and part of the second cystein-rich sequences were removed, bound NGF. However, a mutant lacking all four cysteine-rich sequences was unable to bind NGF. These results show that the four cysteine-rich sequences of the NGF receptor contain the NGF binding domain.

  17. NEUROBIOLOGICAL EFFECTS OF COLCHICINE: MODULATION BY NERVE GROWTH FACTOR

    EPA Science Inventory

    To study the effects of exogenously applied nerve growth factor (NGF) on colchicine-induced neurodegeneration in the dentate gyrus of the rat hippocampal formation, male Fischer 344 rats (n=75) weighing 275-325 grams received colchicine [COLCH; 2.5 ug/site in 0.5 ul of artificial...

  18. Nerve Growth Factor Decreases in Sympathetic and Sensory Nerves of Rats with Chronic Heart Failure

    PubMed Central

    Lu, Jian

    2014-01-01

    Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6–20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185

  19. Nerve growth factor mRNA in brain: localization by in situ hybridization

    SciTech Connect

    Rennert, P.D.; Heinrich, G.

    1986-07-31

    Nerve Growth Factor is a 118 amino acid polypeptide that plays an important role in the differentiation and survival of neurons. The recent discovery that a mRNA that encodes beta Nerve Growth Factor is present in brain suggests that the Nerve Growth Factor gene may not only regulate gene expression of peripheral but also of central neurons. To identify the site(s) of Nerve Growth Factor mRNA production in the brain and to determine which cells express the Nerve Growth Factor gene, the technique of in situ hybridization was employed. A 32P-labeled RNA probe complementary to Nerve Growth Factor mRNA hybridized to cells in the stratum granulosum of the dentate gyrus and the stratum pyramidale of the hippocampus. These observations identify for the first time cellular sites of Nerve Growth Factor gene expression in the central nervous system, and suggest that Nerve Growth Factor mRNA is produced by neurons.

  20. Nerve Growth Factor: A Focus on Neuroscience and Therapy

    PubMed Central

    Aloe, Luigi; Rocco, Maria Luisa; Omar Balzamino, Bijorn; Micera, Alessandra

    2015-01-01

    Nerve growth factor (NGF) is the firstly discovered and best characterized neurotrophic factor, known to play a critical protective role in the development and survival of sympathetic, sensory and forebrain cholinergic neurons. NGF promotes neuritis outgrowth both in vivo and in vitro and nerve cell recovery after ischemic, surgical or chemical injuries. Recently, the therapeutic property of NGF has been demonstrated on human cutaneous and corneal ulcers, pressure ulcer, glaucoma, maculopathy and retinitis pigmentosa. NGF eye drops administration is well tolerated, with no detectable clinical evidence of systemic or local adverse effects. The aim of this review is to summarize these biological properties and the potential clinical development of NGF. PMID:26411962

  1. Biochemical and biological properties of the nerve growth factor receptor

    SciTech Connect

    Taniuchi, M.

    1988-01-01

    We have utilized a monoclonal antibody (192-IgG) to study the rat nerve growth factor receptor. After intraocular injection, {sup 125}I-192-IgG was retrogradely transported in sympathetic neuronal axons to the superior cervical ganglion. When the sciatic nerve was ligated to induce the accumulation of axonally transported materials, 192-IgG immunostaining was observed on both sides of the ligature, indicating that NGF receptors are transported in both orthograde and retrograde directions. By using {sup 125}I-NGF crosslinking and 192-IgG immunoprecipitation, we detected receptor molecules throughout the rat brain, thereby supporting the hypothesis that NGF is active in the central nervous system. We also discovered that sciatic nerve transection leads to a dramatic increase in the amount of NGF receptor found in the distal portion of the nerve. Immunostaining revealed that all Schwann cells in the distal axotomized nerve were expressing NGF receptors. We examined phosphorylation of NGF receptor in cultured sympathetic neurons and PC12 cells. We also examined pharmacological effects of 192-IgG. Systemic injection of 192-IgG into neonatal rats caused a permanent partial sympathectomy in a dose-dependent manner; a maximum of 50% of the cells were killed.

  2. Effects of medium flow on axon growth with or without nerve growth factor.

    PubMed

    Kumamoto, Junichi; Kitahata, Hiroyuki; Goto, Makiko; Nagayama, Masaharu; Denda, Mitsuhiro

    2015-09-11

    Axon growth is a crucial process in regeneration of damaged nerves. On the other hand, elongation of nerve fibers in the epidermis has been observed in skin of atopic dermatitis patients. Thus, regulation of nerve fiber extension might be an effective strategy to accelerate nerve regeneration and/or to reduce itching in pruritus dermatosis. We previously demonstrated that neurons and epidermal keratinocytes similarly contain multiple receptors that are activated by various environmental factors, and in particular, keratinocytes are influenced by shear stress. Thus, in the present study, we evaluated the effects of micro-flow of the medium on axon growth in the presence or absence of nerve growth factor (NGF), using cultured dorsal-root-ganglion (DRG) cells. The apparatus, AXIS™, consists of two chambers connected by a set of microgrooves, through which signaling molecules and axons, but not living cells, can pass. When DRG cells were present in chamber 1, NGF was present in chamber 2, and micro-flow was directed from chamber 1 to chamber 2, axon growth was significantly increased compared with other conditions. Acceleration of axon growth in the direction of the micro-flow was also observed in the absence of NGF. These results suggest that local micro-flow might significantly influence axon growth. PMID:26212442

  3. Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density.

    PubMed

    Hirth, Michael; Rukwied, Roman; Gromann, Alois; Turnquist, Brian; Weinkauf, Benjamin; Francke, Klaus; Albrecht, Philip; Rice, Frank; Hägglöf, Björn; Ringkamp, Matthias; Engelhardt, Maren; Schultz, Christian; Schmelz, Martin; Obreja, Otilia

    2013-11-01

    Nerve growth factor (NGF) is involved in the long-term sensitization of nociceptive processing linked to chronic pain. Functional and structural ("sprouting") changes can contribute. Thus, humans report long-lasting hyperalgesia to mechanical and electrical stimulation after intradermal NGF injection and NGF-induced sprouting has been reported to underlie cancer bone pain and visceral pain. Using a human-like animal model we investigated the relationship between the structure and function of unmyelinated porcine nociceptors 3 weeks after intradermal NGF treatment. Axonal and sensory characteristics were studied by in vivo single-fiber electrophysiology and immunohistochemistry. C fibers recorded extracellularly were classified based on mechanical response and activity-dependent slowing (ADS) of conduction velocity. Intraepidermal nerve fiber (IENF) densities were assessed by immunohistochemistry in pigs and in human volunteers using the same NGF model. NGF increased conduction velocity and reduced ADS and propagation failure in mechano-insensitive nociceptors. The proportion of mechano-sensitive C nociceptors within NGF-treated skin areas increased from 45.1% (control) to 71% and their median mechanical thresholds decreased from 40 to 20 mN. After NGF application, the mechanical receptive fields of nociceptors increased from 25 to 43 mm(2). At the structural level, however, IENF density was not increased by NGF. In conclusion, intradermal NGF induces long-lasting axonal and mechanical sensitization in porcine C nociceptors that corresponds to hyperalgesia observed in humans. Sensitization is not accompanied by increased IENF density, suggesting that NGF-induced hyperalgesia might not depend on changes in nerve fiber density but could be linked to the recruitment of previously silent nociceptors. PMID:23891896

  4. Induction of nerve growth factor receptors on cultured human melanocytes

    SciTech Connect

    Peacocke, M.; Yaar, M.; Mansur, C.P.; Chao, M.V.; Gilchrest, B.A. )

    1988-07-01

    Normal differentiation and malignant transformation of human melanocytes involve a complex series of interactions during which both genetic and environmental factors play roles. At present, the regulation of these processes is poorly understood. The authors have induced the expression of nerve growth factor (NGF) receptors on cultured human melanocytes with phorbol 12-tetradecanoate 13-acetate and have correlated this event with the appearance of a more differentiated, dendritic morphology. Criteria for NGF receptor expression included protein accumulation and cell-surface immunofluorescent staining with a monoclonal antibody directed against the human receptor and induction of the messenger RNA species as determined by blot-hybridization studies. The presence of the receptor could also be induced by UV irradiation or growth factor deprivation. The NGF receptor is inducible in cultured human melanocytes, and they suggest that NGF may modulate the behavior of this neural crest-derived cell in the skin.

  5. A Review of Bioactive Release from Nerve Conduits as a Neurotherapeutic Strategy for Neuronal Growth in Peripheral Nerve Injury

    PubMed Central

    Choonara, Yahya E.; Bijukumar, Divya; du Toit, Lisa C.

    2014-01-01

    Peripheral nerve regeneration strategies employ the use of polymeric engineered nerve conduits encompassed with components of a delivery system. This allows for the controlled and sustained release of neurotrophic growth factors for the enhancement of the innate regenerative capacity of the injured nerves. This review article focuses on the delivery of neurotrophic factors (NTFs) and the importance of the parameters that control release kinetics in the delivery of optimal quantities of NTFs for improved therapeutic effect and prevention of dose dumping. Studies utilizing various controlled-release strategies, in attempt to obtain ideal release kinetics, have been reviewed in this paper. Release strategies discussed include affinity-based models, crosslinking techniques, and layer-by-layer technologies. Currently available synthetic hollow nerve conduits, an alternative to the nerve autografts, have proven to be successful in the bridging and regeneration of primarily the short transected nerve gaps in several patient cases. However, current research emphasizes on the development of more advanced nerve conduits able to simulate the effectiveness of the autograft which includes, in particular, the ability to deliver growth factors. PMID:25143934

  6. Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

    PubMed Central

    Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.

    2013-01-01

    Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. PMID:23659607

  7. Mast Cells Synthesize, Store, and Release Nerve Growth Factor

    NASA Astrophysics Data System (ADS)

    Leon, A.; Buriani, A.; dal Toso, R.; Fabris, M.; Romanello, S.; Aloe, L.; Levi-Montalcini, R.

    1994-04-01

    Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions are typically associated with rapid mast cell activation and NGF accumulation in inflammatory exudates, we hypothesized that mast cells may be capable of producing NGF. Here we report that (i) NGF mRNA is expressed in adult rat peritoneal mast cells; (ii) anti-NGF antibodies clearly stain vesicular compartments of purified mast cells and mast cells in histological sections of adult rodent mesenchymal tissues; and (iii) medium conditioned by peritoneal mast cells contains biologically active NGF. Mast cells thus represent a newly recognized source of NGF. The known actions of NGF on peripheral nerve fibers and immune cells suggest that mast cell-derived NGF may control adaptive/reactive responses of the nervous and immune systems toward noxious tissue perturbations. Conversely, alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature.

  8. Mouse nerve growth factor gene: structure and expression.

    PubMed Central

    Selby, M J; Edwards, R; Sharp, F; Rutter, W J

    1987-01-01

    The organization and biologically significant sequences of the entire mouse nerve growth factor (NGF) gene have been determined. The gene spans 45 kilobases and contains several small 5' exons. Transcription of the gene results in four different mRNA species, which can be accounted for by alternative splicing and independent initiation from two promoters. These transcripts encode proteins which have divergent N termini and the NGF moiety at their C termini. The levels of the various NGF transcripts have been determined in different tissues and throughout postnatal development. We have also examined the expression of these transcripts in the brain in response to specific early sensory deprivation. The results suggest that the expression of NGF mRNA during postnatal development is regulated independently of the formation of complex neural networks. Images PMID:3670305

  9. Nerve growth factor-induced migration of endothelial cells.

    PubMed

    Dollé, Jean-Pierre; Rezvan, Amir; Allen, Fred D; Lazarovici, Philip; Lelkes, Peter I

    2005-12-01

    Nerve growth factor (NGF) is a well known neurotropic and neurotrophic agonist in the nervous system, which recently was shown to also induce angiogenic effects in endothelial cells (ECs). To measure NGF effects on the migration of cultured ECs, an important step in neoangiogenesis, we optimized an omnidirectional migration assay using human aortic endothelial cells (HAECs) and validated the assay with human recombinant basic fibroblast growth factor (rhbFGF) and human recombinant vascular endothelial growth factor (rhVEGF). The potencies of nerve growth factor purified from various species (viper, mouse, and recombinant human) to stimulate HAEC migration was similar to that of VEGF and basic fibroblast growth factor (bFGF) (EC50 of approximately 0.5 ng/ml). Recombinant human bFGF was significantly more efficacious than either viper NGF or rhVEGF, both of which stimulated HAEC migration by approximately 30% over basal spontaneous migration. NGF-mediated stimulation of HAEC migration was completely blocked by the NGF/TrkA receptor antagonist K252a [(8R*,9S*,11S*)-(/)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,-8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(c,d,e)trindene-1-one] (30 nM) but not by the VEGF/Flk receptor antagonist SU-5416 [3-[(2,4-dimethylpyrrol-5-yl) methylidenyl]-indolin-2-one] (250 nM), indicating a direct effect of NGF via TrkA receptor activation on HAEC migration. Viper NGF stimulation of HAEC migration was additively increased by either rhVEGF or rhbFGF, suggesting a potentiating interaction between their tyrosine kinase receptor signaling pathways. Viper NGF represents a novel pharmacological tool to investigate possible TrkA receptor subtypes in endothelial cells. The ability of NGF to stimulate migration of HAEC cells in vitro implies that this factor may play an important role in the cardiovascular system besides its well known effects in the nervous system. PMID:16123305

  10. Nerve growth factor enhances Clara cell proliferation after lung injury.

    PubMed

    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

    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

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

    PubMed Central

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

    2013-01-01

    Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkANTR and p75NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A. PMID:24244623

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

    NASA Astrophysics Data System (ADS)

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

    1985-07-01

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

  13. Retrograde axonal transport of /sup 125/I-nerve growth factor in rat ileal mesenteric nerves. Effect of streptozocin diabetes

    SciTech Connect

    Schmidt, R.E.; Plurad, S.B.; Saffitz, J.E.; Grabau, G.G.; Yip, H.K.

    1985-12-01

    The retrograde axonal transport of intravenously (i.v.) administered /sup 125/I-nerve growth factor (/sup 125/I-NGF) was examined in mesenteric nerves innervating the small bowel of rats with streptozocin (STZ) diabetes using methods described in detail in the companion article. The accumulation of /sup 125/I-NGF distal to a ligature on the ileal mesenteric nerves of diabetic animals was 30-40% less than in control animals. The inhibition of accumulation of /sup 125/I-NGF in diabetic animals was greater at a ligature tied 2 h after i.v. administration than at a ligature tied after 14 h, which suggests that the diabetic animals may have a lag in initiation of NGF transport in the terminal axon or retardation of transport at some site along the axon. The /sup 125/I-NGF transport defect was observed as early as 3 days after the induction of diabetes, a time before the development of structural axonal lesions, and did not worsen at later times when dystrophic axonopathy is present. Both the ileal mesenteric nerves, which eventually develop dystrophic axonopathy in experimental diabetes, and the jejunal mesenteric nerves, which never develop comparable structural alterations, showed similar /sup 125/I-NGF transport deficits, suggesting that the existence of the transport abnormality does not predict the eventual development of dystrophic axonal lesions. Autoradiographic localization of /sup 125/I-NGF in the ileal mesenteric nerves of animals that had been diabetic for 11-13 mo demonstrated decreased amounts of /sup 125/I-NGF in transit in unligated paravascular nerve fascicles. There was, however, no evidence for focal retardation of transported /sup 125/I-NGF at the sites of dystrophic axonal lesions.

  14. Anti-nerve growth factor in pain management: current evidence

    PubMed Central

    Chang, David S; Hsu, Eugene; Hottinger, Daniel G; Cohen, Steven P

    2016-01-01

    There continues to be an unmet need for safe and effective pain medications. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) dominate the clinical landscape despite limited effectiveness and considerable side-effect profiles. Although significant advancements have identified myriad potential pain targets over the past several decades, the majority of new pain pharmacotherapies have failed to come to market. The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the US Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established. PMID:27354823

  15. Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice

    PubMed Central

    Ma, Chi Him Eddie; Omura, Takao; Cobos, Enrique J.; Latrémolière, Alban; Ghasemlou, Nader; Brenner, Gary J.; van Veen, Ed; Barrett, Lee; Sawada, Tomokazu; Gao, Fuying; Coppola, Giovanni; Gertler, Frank; Costigan, Michael; Geschwind, Dan; Woolf, Clifford J.

    2011-01-01

    Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth. PMID:21965333

  16. The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

    PubMed Central

    Pandey, Rahul; Blanco, Jorge; Udolph, Gerald

    2011-01-01

    During development, the growth of the animal body is accompanied by a concomitant elongation of the peripheral nerves, which requires the elongation of integrated nerve fibers and the axons projecting therein. Although this process is of fundamental importance to almost all organisms of the animal kingdom, very little is known about the mechanisms regulating this process. Here, we describe the identification and characterization of novel mutant alleles of GlcAT-P, the Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P mutants reveal shorter larval peripheral nerves and an elongated ventral nerve cord (VNC). We show that GlcAT-P is expressed in a subset of neurons in the central brain hemispheres, in some motoneurons of the ventral nerve cord as well as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants the VNC is under tension of shorter peripheral nerves suggesting that the VNC elongates as a consequence of tension imparted by retarded peripheral nerve growth during larval development. We also provide evidence that for growth of peripheral nerve fibers GlcAT-P is critically required in hemocytes; however, glial cells are also important in this process. The glial specific repo gene acts as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P mutant background enhances VNC elongation. We propose a model in which hemocytes are required for aspects of glial cell biology which in turn affects the elongation of peripheral nerves during larval development. Our data also identifies GlcAT-P as a first candidate gene involved in growth of integrated peripheral nerves and therefore establishes Drosophila as an amenable in-vivo model system to study this process at the cellular and molecular level in more detail. PMID:22132223

  17. Influence of congenital facial nerve palsy on craniofacial growth in craniofacial microsomia.

    PubMed

    Choi, Jaehoon; Park, Sang Woo; Kwon, Geun-Yong; Kim, Sang-Hyun; Hur, Ji An; Baek, Seung-Hak; Kim, Jae Chan; Choi, Tae Hyun; Kim, Sukwha

    2014-11-01

    Facial muscles are of major importance in human craniofacial growth and development. The purpose of our study was to investigate whether congenital facial nerve palsy influences craniofacial growth in craniofacial microsomia. Fifty-one patients with unilateral craniofacial microsomia and no history of craniofacial skeletal surgery whose radiographs were taken after craniofacial growth was complete were included in this study. These patients were divided into groups in which the facial nerve was involved or uninvolved. The authors evaluated a total of seven measurement items to analyze the midface and mandibular asymmetry. Twenty patients had facial nerve involvement, and 31 had no involvement. None of the measurement items revealed any significant differences between the facial nerve-involved group and the uninvolved group within the same modified Pruzansky grade. There was no correlation between the type of facial nerve involvement and the measurement items. In relationships among the measurement items within each group, maxillary asymmetry was indirectly correlated with mandibular asymmetry or midline deviation through the occlusal plane angle in the uninvolved groups. However, in the facial nerve-involved group, the relationships disappeared. When the correlations in the facial nerve-involved group were compared with those of the uninvolved group, the relationships in the uninvolved group appeared more significant than in the facial nerve-involved group. The loss of relationships between the upper and lower jaw in the facial nerve-involved group might have been caused by subtle changes, which occur in midfacial bones and in the mandible due to facial nerve palsy. The main limitation of our study is that aside from facial nerve palsy, craniofacial microsomia has many factors that can influence craniofacial growth, such as hypoplasia of the mandibular condyle and soft tissue deficiencies. PMID:25210001

  18. Growth-regulated synthesis and secretion of biologically active nerve growth factor by human keratinocytes.

    PubMed

    Di Marco, E; Marchisio, P C; Bondanza, S; Franzi, A T; Cancedda, R; De Luca, M

    1991-11-15

    Nerve growth factor (NGF) transcripts were identified in normal human keratinocytes in primary and secondary culture. The expression of the NGF mRNA was strongly down-regulated by corticosteroids and was maximal when keratinocytes were in the exponential phase of growth. Immunofluorescence studies on growing keratinocytes colonies and on elutriated keratinocytes obtained from growing colonies and mature stratified epithelium showed specific staining of the Golgi apparatus only in basal keratinocytes in the exponential phase of growth. The keratinocyte-derived NGF was secreted in a biologically active form as assessed by neurite induction in sensory neurons obtained from chick embryo dorsal root ganglia. Based on these data we suggest that the basal keratinocyte is the cell synthesizing and secreting NGF in the human adult epidermis. The paracrine secretion of NGF by keratinocytes might have a major role in regulating innervation, lymphocyte function, and melanocyte growth and differentiation in epidermal morphogenesis as well as during wound healing. PMID:1718982

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

    PubMed Central

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

    2011-01-01

    Transplantation of adipose-derived mesenchymal stem cells (ASCs) induces tissue regeneration by accelerating the growth of blood vessels and nerve. However, mechanisms by which they accelerate the growth of nerve fibers are only partially understood. We used transplantation of ASCs with subcutaneous matrigel implants (well-known in vivo model of angiogenesis) and model of mice limb reinnervation to check the influence of ASC on nerve growth. Here we show that ASCs stimulate the regeneration of nerves in innervated mice's limbs and induce axon growth in subcutaneous matrigel implants. To investigate the mechanism of this action we analyzed different properties of these cells and showed that they express numerous genes of neurotrophins and extracellular matrix proteins required for the nerve growth and myelination. Induction of neural differentiation of ASCs enhances production of brain-derived neurotrophic factor (BDNF) as well as ability of these cells to induce nerve fiber growth. BDNF neutralizing antibodies abrogated the stimulatory effects of ASCs on the growth of nerve sprouts. These data suggest that ASCs induce nerve repair and growth via BDNF production. This stimulatory effect can be further enhanced by culturing the cells in neural differentiation medium prior to transplantation. PMID:21423756

  20. Genes that guide growth cones along the C. elegans ventral nerve cord.

    PubMed

    Wightman, B; Baran, R; Garriga, G

    1997-07-01

    During nervous system development, growth cone pioneering and fasciculation contribute to nerve bundle structure. Pioneer growth cones initially navigate along neuroglia to establish an axon scaffold that guides later extending growth cones. In C. elegans, the growth cone of the PVPR neuron pioneers the left ventral nerve cord bundle, providing a path for the embryonic extensions of the PVQL and AVKR growth cones. Later during larval development, the HSNL growth cone follows cues in the left ventral nerve cord bundle provided by the PVPR and PVQL axons. Here we show that mutations in the genes enu-1, fax-1, unc-3, unc-30, unc-42 and unc-115 disrupt pathfinding of growth cones along the left ventral nerve cord bundle. Our results indicate that unc-3 and unc-30 function in ventral nerve cord pioneering and that enu-1, fax-1, unc-42 and unc-115 function in recognition of the PVPR and PVQL axons by the AVKR and HSNL growth cones. PMID:9216999

  1. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    PubMed

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-01

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries. PMID:26671004

  2. Nerve Growth Factor Inhibits Sympathetic Neurons' Response to an Injury Cytokine

    NASA Astrophysics Data System (ADS)

    Shadiack, Annette M.; Vaccariello, Stacey A.; Sun, Yi; Zigmond, Richard E.

    1998-06-01

    Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor. It is shown in the present study that no stimulation of galanin expression occurs following direct application of LIF to intact neurons in the superior cervical sympathetic ganglion. Injection of animals with an antiserum to nerve growth factor concomitant with the application of LIF, on the other hand, does stimulate galanin expression. The data suggest that the response of neurons to an injury factor, LIF, is affected by whether the neurons still receive trophic signals from their targets.

  3. Nerve growth factor promotes in vitro proliferation of neural stem cells from tree shrews

    PubMed Central

    Xiong, Liu-lin; Chen, Zhi-wei; Wang, Ting-hua

    2016-01-01

    Neural stem cells promote neuronal regeneration and repair of brain tissue after injury, but have limited resources and proliferative ability in vivo. We hypothesized that nerve growth factor would promote in vitro proliferation of neural stem cells derived from the tree shrews, a primate-like mammal that has been proposed as an alternative to primates in biomedical translational research. We cultured neural stem cells from the hippocampus of tree shrews at embryonic day 38, and added nerve growth factor (100 μg/L) to the culture medium. Neural stem cells from the hippocampus of tree shrews cultured without nerve growth factor were used as controls. After 3 days, fluorescence microscopy after DAPI and nestin staining revealed that the number of neurospheres and DAPI/nestin-positive cells was markedly greater in the nerve growth factor-treated cells than in control cells. These findings demonstrate that nerve growth factor promotes the proliferation of neural stem cells derived from tree shrews. PMID:27212919

  4. Nerve growth factor promotes in vitro proliferation of neural stem cells from tree shrews.

    PubMed

    Xiong, Liu-Lin; Chen, Zhi-Wei; Wang, Ting-Hua

    2016-04-01

    Neural stem cells promote neuronal regeneration and repair of brain tissue after injury, but have limited resources and proliferative ability in vivo. We hypothesized that nerve growth factor would promote in vitro proliferation of neural stem cells derived from the tree shrews, a primate-like mammal that has been proposed as an alternative to primates in biomedical translational research. We cultured neural stem cells from the hippocampus of tree shrews at embryonic day 38, and added nerve growth factor (100 μg/L) to the culture medium. Neural stem cells from the hippocampus of tree shrews cultured without nerve growth factor were used as controls. After 3 days, fluorescence microscopy after DAPI and nestin staining revealed that the number of neurospheres and DAPI/nestin-positive cells was markedly greater in the nerve growth factor-treated cells than in control cells. These findings demonstrate that nerve growth factor promotes the proliferation of neural stem cells derived from tree shrews. PMID:27212919

  5. Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells☆

    PubMed Central

    Yang, Xiaochun; Duan, Xuanchu

    2013-01-01

    A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline (90 mg/kg) was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells, glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis. PMID:25206672

  6. Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels.

    PubMed

    Conovaloff, Aaron W; Beier, Brooke L; Irazoqui, Pedro P; Panitch, Alyssa

    2011-01-01

    Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. Furthermore, cultures of chick dorsal root ganglia in gels of hyaluronic acid or chondroitin sulfate revealed enhanced growth in chondroitin sulfate gels only upon addition of peptide. Taken together, these results suggest a synergistic nerve growth factor-binding activity between this peptide and chondroitin sulfate. PMID:23507745

  7. Transforming Growth Factor-β Promotes Axonal Regeneration After Chronic Nerve Injury.

    PubMed

    Sulaiman, Wale A R

    2016-04-01

    When spinal cord injury (SCI) occurs, injured cells must survive and regenerate to close gaps caused by the injury and to create functional motor units. After peripheral nerve injury, Wallerian degeneration in the distal nerve stump creates a neurotrophic and growth-supportive environment for injured neurons and axons via Schwann cells and secreted cytokines/neurotrophins. In both SCI and peripheral nerve injury, injured motor and sensory neurons must regenerate axons, eventually reaching and reinnervating target tissue (SDC Figure 1, http://links.lww.com/BRS/B116). This process is often unsuccessful after SCI, and the highly complex anatomy of branching axons and nerves in the peripheral nervous system leads to slow recovery of function, even with careful and appropriate techniques. PMID:27015069

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

    NASA Astrophysics Data System (ADS)

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

    2009-11-01

    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.

  9. Experimental Research on Differentiation-Inducing Growth of Nerve Lateral Bud by HUC-MSCs Chitosan Composite Conduit.

    PubMed

    Xiao, Qiang; Zhang, Xuepu; Wu, Yuexin

    2015-11-01

    This study is intended to explore the role of human umbilical-cord-derived mesenchymal stem cells (HUC-MSCs) in nerve end-to-side anastomosis, as well as in the induction and promotion of growth of nerve lateral bud. The chitosan nerve conduit was prepared based on the biological characteristics of chitosan, and the nerve conduit was filled with HUC-MSCs, and was used to bridge the nerve end-to-side anastomotic stoma. The experimental animals were randomly assigned into three groups (10 in each group), and the nerve end-to-side anastomosis was conducted: (1) group A (control group): traditional tibial nerve-common peroneal nerve end-to-side anastomosis; (2) group B (experimental group 1): tibial nerve-common peroneal nerve end-to-side anastomotic stoma bridged with chitosan nerve conduit; (3) group C (experimental group 2): tibial nerve-common peroneal nerve end-to-side anastomotic stoma bridged by chitosan nerve conduit filled with HUC-MSCs. General morphological observation, nerve electrophysiology, and anti-S-100 immunohistochemistry were performed. All experimental animals survived, and no infections were found at operative incisions. The nerve continuity was in good condition through visual observation when sampling, which is mild adhesion to the surrounding tissue and easy to be separated. 12 W HUC-MSCs chitosan composite nerve conduits were degraded completely after operation. Electrophysiological test showed that the nerve conduction velocity (NCV) in group C was significantly higher than that in group A or group B (p < 0.01). There were no significant differences between NCVs of group A and group B. Toluidine blue staining and transmission electron microscope showed that the number of the medullated fibers and the myelin sheath thickness in group C were larger than those in group A or B. There were no significant differences between the numbers of the medullated fibers and between the myelin sheath thicknesses of groups A and B. By means of anti-S-100

  10. Scaffolds from alternating block polyurethanes of poly(ɛ-caprolactone) and poly(ethylene glycol) with stimulation and guidance of nerve growth and better nerve repair than autograft.

    PubMed

    Niu, Yuqing; Li, Linjing; Chen, Kevin C; Chen, Feiran; Liu, Xiangyu; Ye, Jianfu; Li, Wei; Xu, Kaitian

    2015-07-01

    Nerve repair scaffolds from novel alternating block polyurethanes (PUCL-alt-PEG) based on PCL and PEG without additional growth factors or proteins were prepared by a particle leaching method. The scaffolds have pore size 10-20 µm and porosity 92%. Mechanical tests showed that the polyurethane scaffolds have maximum loads of 5.97 ± 0.35 N and maximal stresses of 8.84 ± 0.5 MPa. Histocompatiblity of the nerve repair scaffolds was tested in a SD rat model for peripheral nerve defect treatment. Two types of treatments including PUCL-alt-PEG scaffolds and autografts were compared in rat model. After 32 weeks, bridging of a 12 mm defect gap by the regenerated nerve was observed in all rats. The nerve regeneration was systematically characterized by sciatic function index (SFI), electrophysiology, histological assessment including HE staining, immunohistochemistry, ammonia sliver staining, Masson's trichrome staining and TEM observation. Results revealed that nerve repair scaffolds from PUCL-alt-PEG exhibit better regeneration effects compared to autografts. Electrophysiological recovery was seen in 90% and 87% of rats in PUCL-alt-PEG and autograft groups respectively. Biodegradation in vitro and in vivo shows good degradation match of PUCL-alt-PEG scaffolds with nerve regeneration. It demonstrates that plain nerve repair scaffolds from PUCL-alt-PEG biomaterials can achieve peripheral nerve regeneration satisfactorily. PMID:25410272

  11. Growth of injured rabbit optic axons within their degenerating optic nerve

    SciTech Connect

    Lavie, V.; Murray, M.; Solomon, A.; Ben-Bassat, S.; Belkin, M.; Rumelt, S.; Schwartz, M. )

    1990-08-15

    Spontaneous growth of axons after injury is extremely limited in the mammalian central nervous system (CNS). It is now clear, however, that injured CNS axons can be induced to elongate when provided with a suitable environment. Thus injured CNS axons can elongate, but they do not do so unless their environment is altered. We now show apparent regenerative growth of injured optic axons. This growth is achieved in the adult rabbit optic nerve by the use of a combined treatment consisting of: (1) supplying soluble substances originating from growing axons to be injured rabbit optic nerves, and (2) application of low energy He-Ne laser irradiation, which appears to delay degenerative changes in the injured axons. Two to 8 weeks after this treatment, unmyelinated and thinly myelinated axons are found at the lesion site and distal to it. Morphological and immunocytochemical evidence indicate that these thinly myelinated and unmyelinated axons are growing in close association with glial cells. Only these axons are identified as being growing axons. These newly growing axons transverse the site of injury and extend into the distal stump of the nerve, which contains degenerating axons. Axons of this type could be detected distal to the lesion only in nerves subjected to the combined treatment. No unmyelinated or thinly myelinated axons in association with glial cells were seen at 6 or 8 weeks postoperatively in nerves that were not treated, or in nerves in which the two stumps were completely disconnected. Two millimeters distal to the site of injury, the growing axons are confined to a compartment comprising 5%-30% of the cross section of the nerve. A temporal analysis indicates that axons have grown as far as 6 mm distal to the site of injury, by 8 weeks postoperatively.

  12. Nerve growth factor: role in growth, differentiation and controlling cancer cell development.

    PubMed

    Aloe, Luigi; Rocco, Maria Luisa; Balzamino, Bijorn Omar; Micera, Alessandra

    2016-01-01

    Recent progress in the Nerve Growth Factor (NGF) research has shown that this factor acts not only outside its classical domain of the peripheral and central nervous system, but also on non-neuronal and cancer cells. This latter observation has led to divergent hypothesis about the role of NGF, its specific distribution pattern within the tissues and its implication in induction as well as progression of carcinogenesis. Moreover, other recent studies have shown that NGF has direct clinical relevance in certain human brain neuron degeneration and a number of human ocular disorders. These studies, by suggesting that NGF is involved in a plethora of physiological function in health and disease, warrant further investigation regarding the true role of NGF in carcinogenesis. Based on our long-lasting experience in the physiopathology of NGF, we aimed to review previous and recent in vivo and in vitro NGF studies on tumor cell induction, progression and arrest. Overall, these studies indicate that the only presence of NGF is unable to generate cell carcinogenesis, both in normal neuronal and non-neuronal cells/tissues. However, it cannot be excluded the possibility that the co-expression of NGF and pro-carcinogenic molecules might open to different consequence. Whether NGF plays a direct or an indirect role in cell proliferation during carcinogenesis remains to demonstrate. PMID:27439311

  13. Mesenchymal stem cells modified with nerve growth factor improve recovery of the inferior alveolar nerve after mandibular distraction osteogenesis in rabbits.

    PubMed

    Wang, L; Zhao, Y; Cao, J; Yang, X; Lei, D

    2015-03-01

    Distraction osteogenesis is widely used in the treatment of bony deformities and defects. However, injury to the inferior alveolar nerve is a concern. Our aim was to investigate the feasibility of using lentiviral-mediated human nerve growth factor beta (hNGFβ) of the inferior alveolar nerve in mandibular distraction osteogenesis in rabbits. To achieve this, mesenchymal stem cells (MSC) from the bone marrow of rabbit mandibles were isolated and genetically engineered using recombinant lentiviral vector containing hNGFβ. Twenty New Zealand white rabbits underwent mandibular distraction osteogenesis, and 5 million MSC transduced with hNGFβ-vector or control vector were transplanted around the nerve in the gap where the bone had been fractured during the operation (n=10 in each group). After gradual distraction, samples of the nerve were harvested for histological and histomorphometric analysis. We found that the genetically engineered MSC transduced by the lentiviral vector were able to secrete hNGFβ at physiologically relevant concentrations as measured by ELISA. Histological examination of the nerve showed more regenerating nerve fibres and less myelin debris in the group in which hNGFβ-modified MSC had been implanted than in the control group. Histomorphometric analysis of the nerve showed increased density of myelinated fibres in the group in which hNGFβ-modified MSC had been implanted than in the control group. The data suggest that implantation of hNGFβ-modified MSC can accelerate the morphological recovery of the inferior alveolar nerve during mandibular distraction osteogenesis in rabbits. The use of lentiviral-mediated gene treatment to deliver hNGFβ through MSC may be a promising way of minimising injury to the nerve. PMID:25600702

  14. Transforming growth factor-β3 promotes facial nerve injury repair in rabbits

    PubMed Central

    WANG, YANMEI; ZHAO, XINXIANG; HUOJIA, MUHTER; XU, HUI; ZHUANG, YOUMEI

    2016-01-01

    The present study investigated the effects of transforming growth factor (TGF)-β3 on the regeneration of facial nerves in rabbits. A total of 20 adult rabbits were randomly divided into three equal groups: Normal control (n=10), surgical control (n=10) and TGF-β3 treatment (n=10). The total number and diameter of the regenerated nerve fibers was significantly increased in the TGF-β3 treatment group, as compared with in the surgical control group (P<0.01). Furthermore, in the TGF-β3 treatment group, the epineurial repair of the facial nerves was intact and the nerve fibers, which were arranged in neat rows, were morphologically intact with visible myelin swelling. However, in the surgical control group, the epineurial repair was incomplete, as demonstrated by: Atrophic nerve fibers, partially disappeared axons and myelin of uneven thickness with fuzzy borders. Electron microscopy demonstrated that the regenerated fibers in the TGF-β3 treatment group were predominantly myelinated, with clear-layered myelin sheath structures and axoplasms rich in organelles. Although typical layered myelin sheath structures were observed in the surgical control group, the myelin sheaths of the myelinated nerve fibers were poorly developed and few organelles were detected in the axoplasms. Neuro-electrophysiological examination demonstrated that, as compared with the surgical control group, the latency period of the action potentials in the TGF-β3 treatment group were shorter, whereas the stimulus amplitudes of the action potentials were significantly increased (P<0.01). The results of the present study suggest that TGF-β3 may improve the regeneration of facial nerves following trauma or injury. PMID:26997982

  15. Erythropoietin promotes peripheral nerve regeneration in rats by upregulating expression of insulin-like growth factor-1

    PubMed Central

    Wang, Wei; Li, Dongsheng; Li, Qing; Wang, Lei; Bai, Guang; Yang, Tao; Li, Qiang; Zhu, Zhitu

    2015-01-01

    Introduction Erythropoietin (EPO) has been shown to have beneficial effects on peripheral nerve damage, but its mechanism of action remains incompletely understood. In this study we hypothesized that EPO promotes peripheral nerve repair via neurotrophic factor upregulation. Material and methods Thirty adult male Wistar rats were employed to establish a sciatic nerve injury model. They were then randomly divided into two groups to be subjected to different treatment: 0.9% saline (group A) and 5000 U/kg EPO (group B). The walking behavior of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by electron microscopy. The expression of insulin-like growth factor-1 (IGF-1) in the injured sciatic nerves was detected by immunohistochemical analysis. Results Compared to saline treatment, EPO treatment led to the growth of myelin sheath, the recovery of normal morphology of axons and Schwann cells, and higher density of myelinated nerve fibers. Erythropoietin treatment promoted the recovery of SFI in the injured sciatic nerves. In addition, EPO treatment led to increased IGF-1 expression in the injured sciatic nerves. Conclusions Erythropoietin may promote peripheral nerve repair in a rat model of sciatic nerve injury through the upregulation of IGF-1 expression. These findings reveal a novel mechanism underlying the neurotrophic effects of EPO. PMID:25995763

  16. Radixin Is Involved in Lamellipodial Stability during Nerve Growth Cone Motility

    PubMed Central

    Castelo, Leslie; Jay, Daniel G.

    1999-01-01

    Immunocytochemistry and in vitro studies have suggested that the ERM (ezrin-radixin-moesin) protein, radixin, may have a role in nerve growth cone motility. We tested the in situ role of radixin in chick dorsal root ganglion growth cones by observing the effects of its localized and acute inactivation. Microscale chromophore-assisted laser inactivation (micro-CALI) of radixin in growth cones causes a 30% reduction of lamellipodial area within the irradiated region whereas all control treatments did not affect lamellipodia. Micro-CALI of radixin targeted to the middle of the leading edge often split growth cones to form two smaller growth cones during continued forward movement (>80%). These findings suggest a critical role for radixin in growth cone lamellipodia that is similar to ezrin function in pseudopodia of transformed fibroblasts. They are consistent with radixin linking actin filaments to each other or to the membrane during motility. PMID:10233159

  17. Molecular cloning of a human gene that is a member of the nerve growth factor family.

    PubMed Central

    Jones, K R; Reichardt, L F

    1990-01-01

    Cell death within the developing vertebrate nervous system is regulated in part by interactions between neurons and their innervation targets that are mediated by neurotrophic factors. These factors also appear to have a role in the maintenance of the adult nervous system. Two neurotrophic factors, nerve growth factor and brain-derived neurotrophic factor, share substantial amino acid sequence identity. We have used a screen that combines polymerase chain reaction amplification of genomic DNA and low-stringency hybridization with degenerate oligonucleotides to isolate human BDNF and a human gene, neurotrophin-3, that is closely related to both nerve growth factor and brain-derived neurotrophic factor. mRNA products of the brain-derived neurotrophic factor and neurotrophin-3 genes were detected in the adult human brain, suggesting that these proteins are involved in the maintenance of the adult nervous system. Neurotrophin-3 is also expected to function in embryonic neural development. Images PMID:2236018

  18. Nerve growth factor antibody exacerbates neuropathological signs of experimental allergic encephalomyelitis in adult lewis rats.

    PubMed

    Micera, A; Properzi, F; Triaca, V; Aloe, L

    2000-05-01

    In this study, experimental allergic encephalomyelitis (EAE) rats and rats exhibiting EAE expressing high circulating anti-nerve growth factor antibody were daily monitored for clinical signs and chronic relapses. Eighty-five days after EAE induction, blood, spinal cord and brain stem were used for histological examination, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) evaluation. The results showed that NGF-deprived rats display more severe clinical signs of disease. These effects were associated with a significant reduction of NGF in the brain stem and spinal cord but not of BDNF, which decreased only in spinal cord. These observations provide additional support to the hypothesis of a protective NGF role in rats exhibiting EAE. PMID:10713350

  19. Changes in myelin sheath thickness and internode geometry in the rabbit phrenic nerve during growth.

    PubMed Central

    Friede, R L; Brzoska, J; Hartmann, U

    1985-01-01

    The rabbit phrenic nerve was studied at seven phases of growth from the newborn to the adult to determine the length of the nerve fibres, the length of the internodes, the fibre calibre, the geometric proportions of the internodes and the thickness of the myelin sheaths. The elongation of the internodes corresponded precisely to the elongation of the nerve, indicating a constant number of approximately 140 internodes per fibre, each internode elongating commensurate with body growth. Internode elongation was accompanied by increases in fibre calibre, but these parameters did not change in precise proportion. The internodes of thick fibres were relatively short for calibre, as defined by the length/diameter quotient. This trend of foreshortening changed during growth. Sheath thickness, defined by the quotient axon diameter/fibre diameter, was determined with a computer-assisted method. Fibres of young rabbits had relatively thin sheaths for axon calibre, compared with adult rabbits. The changes in sheath thickness corresponded to the changes in internode geometry. This was consistent with previous studies showing that elongation or foreshortening of an internode of a given calibre has a slight, but definite effect on the thickness of its myelin sheath. PMID:3870716

  20. Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: A sciatic nerve transection model

    PubMed Central

    Golzadeh, Atefeh; Mohammadi, Rahim

    2016-01-01

    Background: Effects of platelet-derived growth factor B (PDGF-B) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Materials and Methods: Forty-five male, white Wistar rats were divided into three experimental groups (n = 15), randomly: Normal control group (NC), silicon group (SIL), and PDGF-B treated group (SIL/PDGF). In NC group, left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the SIL group, the left sciatic nerve was exposed in the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone conduit and filled with 10 μL phosphate buffered solution. In SIL/PDGF group, the silicon conduit was filled with 10 μL PDGF-B (0.5 ng/mL). Each group was subdivided into three subgroups of five and were studied in 4, 8, 12 weeks after surgery. Results: Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass, and histomorphometric studies showed earlier regeneration of axons in SIL/PDGF than in SIL group (P < 0.05). Conclusion: Local administration of PDGF-B combined with silicon grafting could accelerate functional recovery and may have clinical implications for the surgical management of patients after facial nerve transection. PMID:27274342

  1. Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent.

    PubMed

    Podlasek, Carol A; Ghosh, Rudrani; Onur Cakir, Omer; Bond, Christopher; McKenna, Kevin E; McVary, Kevin T

    2013-11-01

    Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n=39). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS. PMID:23872662

  2. The effects of gradients of nerve growth factor immobilized PCLA scaffolds on neurite outgrowth in vitro and peripheral nerve regeneration in rats.

    PubMed

    Tang, Shuo; Zhu, Jixiang; Xu, Yangbin; Xiang, Andy Peng; Jiang, Mei Hua; Quan, Daping

    2013-09-01

    Introducing concentration gradients of nerve growth factor (NGF) into conduits for repairing of peripheral nerve injury is crucial for nerve regeneration and guidance. Herein, combining differential adsorption of NGF/silk fibroin (SF) coating, the gradient of NGF-immobilized membranes (G-Ms) and nanofibrous nerve conduits (G-nNCs) were successfully fabricated. The efficacy of NGF gradients was confirmed by a quantitative comparison of dorsal root ganglia (DRG) neurite outgrowth on the G-Ms or uniform NGF-immobilized membranes (U-Ms). Significantly, the neurite turning ratio was 0.48 ± 0.11 for G-M group, but it was close to zero for U-M group. The neurite length of DRGs in the middle of the G-Ms was significantly longer than that of U-M group, even though the average NGF concentration was approximated. Furthermore, 12 weeks after implantation in rats with a 14 mm gap of sciatic nerve injury, G-nNCs achieved satisfying outcomes of nerve regeneration associated with morphological and functional improvements, which was superior to that of the uniform NGF-immobilized nNCs (U-nNCs). Sciatic function index (SFI), compound muscle action potentials (CMAPs), total number of myelinated nerve fibers, thickness of myelin sheath were similar for the G-nNCs and autografts, with the G-nNCs having a higher density of axons than the autografts. Our results demonstrated the significant role of introducing NGF gradients into scaffolds in promoting nerve regeneration. PMID:23791502

  3. The myelin oligodendrocyte glycoprotein directly binds nerve growth factor to modulate central axon circuitry

    PubMed Central

    Mei, Feng; Greenfield, Ariele; Jahn, Sarah; Shen, Yun-An A.; Reid, Hugh H.; McKemy, David D.

    2015-01-01

    Myelin oligodendrocyte glycoprotein (MOG) is a central nervous system myelin-specific molecule expressed on the outer lamellae of myelin. To date, the exact function of MOG has remained unknown, with MOG knockout mice displaying normal myelin ultrastructure and no apparent specific phenotype. In this paper, we identify nerve growth factor (NGF) as a binding partner for MOG and demonstrate that this interaction is capable of sequestering NGF from TrkA-expressing neurons to modulate axon growth and survival. Deletion of MOG results in aberrant sprouting of nociceptive neurons in the spinal cord. Binding of NGF to MOG may offer widespread implications into mechanisms that underlie pain pathways. PMID:26347141

  4. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    NASA Technical Reports Server (NTRS)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

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

    PubMed Central

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

    1991-01-01

    We have examined 1,2-diglycerides (DGs) generated in PC12 cells in response to the muscarinic agonist carbachol and compared them with those generated in response to the differentiation factors nerve growth factor and basic fibroblast growth factor. Whereas carbachol stimulates a greater release of inositol phosphates, all three agonists generate similar levels of DGs. In this report, we have analyzed the molecular species of PC12 DGs generated in response to these three agonists. Additionally, we have analyzed the molecular species of PC12 phospholipids. The data indicate that 1) after 1 min of either nerve growth factor or basic fibroblast growth factor stimulation, DGs arise primarily from phosphoinositide hydrolysis; 2) in contrast, after 1 min of carbachol stimulation, DG are generated equally by both phosphoinositide and phosphatidylcholine hydrolysis; and 3) after 15 min of stimulation by any of these agonists, DGs are generated largely by phosphatidylcholine hydrolysis, with a smaller component arising from the phosphoinositides. These results suggest that at least part of the mechanism by which PC12 cells distinguish between different agonists is via alterations in phospholipid sources and kinetics of DG generation. PMID:1892912

  6. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons.

    PubMed

    Murayama, Chiaki; Watanabe, Shimpei; Nakamura, Motokazu; Norimoto, Hisayoshi

    2015-01-01

    Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in "itch-scratch" animal models is under investigation. PMID:26287150

  7. Corneal Sulfated Glycosaminoglycans and Their Effects on Trigeminal Nerve Growth Cone Behavior In Vitro: Roles for ECM in Cornea Innervation

    PubMed Central

    Schwend, Tyler; Deaton, Ryan J.; Zhang, Yuntao; Caterson, Bruce; Conrad, Gary W.

    2012-01-01

    Purpose. Sensory trigeminal nerve growth cones innervate the cornea in a highly coordinated fashion. The purpose of this study was to determine if extracellular matrix glycosaminoglycans (ECM–GAGs), including keratan sulfate (KS), dermatan sulfate (DS), and chondroitin sulfate A (CSA) and C (CSC), polymerized in developing eyefronts, may provide guidance cues to nerves during cornea innervation. Methods. Immunostaining using antineuron-specific-β-tubulin and monoclonal antibodies for KS, DS, and CSA/C was performed on eyefronts from embryonic day (E) 9 to E14 and staining visualized by confocal microscopy. Effects of purified GAGs on trigeminal nerve growth cone behavior were tested using in vitro neuronal explant cultures. Results. At E9 to E10, nerves exiting the pericorneal nerve ring grew as tight fascicles, advancing straight toward the corneal stroma. In contrast, upon entering the stroma, nerves bifurcated repeatedly as they extended anteriorly toward the epithelium. KS was localized in the path of trigeminal nerves, whereas DS and CSA/C–rich areas were avoided by growth cones. When E10 trigeminal neurons were cultured on different substrates comprised of purified GAG molecules, their neurite growth cone behavior varied depending on GAG type, concentration, and mode of presentation (immobilized versus soluble). High concentrations of immobilized KS, DS, and CSA/C inhibited neurite growth to varying degrees. Neurites traversing lower, permissive concentrations of immobilized DS and CSA/C displayed increased fasciculation and decreased branching, whereas KS caused decreased fasciculation and increased branching. Enzymatic digestion of sulfated GAGs canceled their effects on trigeminal neurons. Conclusions. Data herein suggest that GAGs may direct the movement of trigeminal nerve growth cones innervating the cornea. PMID:23132805

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

    NASA Astrophysics Data System (ADS)

    Sandrock, Alfred W.; Matthew, William D.

    1987-10-01

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

  9. The in vitro biological effect of nerve growth factor is inhibited by synthetic peptides.

    PubMed Central

    Longo, F M; Vu, T K; Mobley, W C

    1990-01-01

    Nerve growth factor (NGF)1 is a neurotrophic polypeptide that acts via specific receptors to promote the survival and growth of neurons. To delineate the NGF domain(s) responsible for eliciting biological activity, we synthesized small peptides corresponding to three regions in NGF that are hydrophilic and highly conserved. Several peptides from mouse NGF region 26-40 inhibited the neurite-promoting effect of NGF on sensory neurons in vitro. Inhibition was sequence-specific and could be overcome by increasing the concentration of NGF. Moreover, peptide actions were specific for NGF-mediated events in that they failed to block the neurotrophic activity of ciliary neuronotrophic factor (CNTF) or phorbol 12-myristate 13-acetate (PMA). In spite of the inhibition of NGF activity, peptides did not affect the binding of radiolabeled NGF. These studies define one region of NGF that may be required for neurotrophic activity. Images PMID:2100197

  10. Nerve growth factor regulates synaptophysin expression in developing trigeminal ganglion neurons in vitro.

    PubMed

    Tarsa, L; Balkowiec, A

    2009-02-01

    The role of neuronal growth factors in synaptic maturation of sensory neurons, including trigeminal ganglion (TG) neurons, remains poorly understood. Here, we show that nerve growth factor (NGF) regulates the intracellular distribution of the synaptic vesicle protein synaptophysin (Syp) in newborn rat TG neurons in vitro. While reducing the number of Syp-positive cell bodies, NGF dramatically increases Syp immunoreactivity in both proximal and distal segments of the neurite. Intriguingly, the increase in Syp immunoreactivity occurs only in neuron-enriched cultures, in which the number of non-neuronal cells is significantly reduced. Together, our data indicate that NGF is a candidate molecule involved in early postnatal maturation of TG neurons, including control of presynaptic assembly, and thereby formation of synaptic connections. PMID:19019428

  11. Nerve Growth Factor Regulates Synaptophysin Expression In Developing Trigeminal Ganglion Neurons In Vitro

    PubMed Central

    Tarsa, L.; Balkowiec, A.

    2008-01-01

    The role of neuronal growth factors in synaptic maturation of sensory neurons, including trigeminal ganglion (TG) neurons, remains poorly understood. Here, we show that nerve growth factor (NGF) regulates the intracellular distribution of the synaptic vesicle protein synaptophysin (Syp) in newborn rat TG neurons in vitro. While reducing the number of Syp-positive cell bodies, NGF dramatically increases Syp immunoreactivity in both proximal and distal segments of the neurite. Intriguingly, the increase in Syp immunoreactivity occurs only in neuron-enriched cultures, in which the number of non-neuronal cells is significantly reduced. Together, our data indicate that NGF is a candidate molecule involved in early postnatal maturation of TG neurons, including control of presynaptic assembly, and thereby formation of synaptic connections. PMID:19019428

  12. Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator

    PubMed Central

    Zhou, Xiang; Hao, Qian; Liao, Peng; Luo, Shiwen; Zhang, Minhong; Hu, Guohui; Liu, Hongbing; Zhang, Yiwei; Cao, Bo; Baddoo, Melody; Flemington, Erik K; Zeng, Shelya X; Lu, Hua

    2016-01-01

    Cancer develops and progresses often by inactivating p53. Here, we unveil nerve growth factor receptor (NGFR, p75NTR or CD271) as a novel p53 inactivator. p53 activates NGFR transcription, whereas NGFR inactivates p53 by promoting its MDM2-mediated ubiquitin-dependent proteolysis and by directly binding to its central DNA binding domain and preventing its DNA-binding activity. Inversely, NGFR ablation activates p53, consequently inducing apoptosis, attenuating survival, and reducing clonogenic capability of cancer cells, as well as sensitizing human cancer cells to chemotherapeutic agents that induce p53 and suppressing mouse xenograft tumor growth. NGFR is highly expressed in human glioblastomas, and its gene is often amplified in breast cancers with wild type p53. Altogether, our results demonstrate that cancers hijack NGFR as an oncogenic inhibitor of p53. DOI: http://dx.doi.org/10.7554/eLife.15099.001 PMID:27282385

  13. Beta-nerve growth factor promotes neurogenesis and angiogenesis during the repair of bone defects

    PubMed Central

    Chen, Wei-hui; Mao, Chuan-qing; Zhuo, Li-li; Ong, Joo L.

    2015-01-01

    We previously showed that the repair of bone defects is regulated by neural and vascular signals. In the present study, we examined the effect of topically applied β-nerve growth factor (β-NGF) on neurogenesis and angiogenesis in critical-sized bone defects filled with collagen bone substitute. We created two symmetrical defects, 2.5 mm in diameter, on either side of the parietal bone of the skull, and filled them with bone substitute. Subcutaneously implanted osmotic pumps were used to infuse 10 μg β-NGF in PBS (β-NGF + PBS) into the right-hand side defect, and PBS into the left (control) defect, over the 7 days following surgery. Immunohistochemical staining and hematoxylin-eosin staining were carried out at 3, 7, 14, 21 and 28 days postoperatively. On day 7, expression of β III-tubulin was lower on the β-NGF + PBS side than on the control side, and that of neurofilament 160 was greater. On day 14, β III-tubulin and protein gene product 9.5 were greater on the β-NGF + PBS side than on the control side. Vascular endothelial growth factor expression was greater on the experimental side than the control side at 7 days, and vascular endothelial growth factor receptor 2 expression was elevated on days 14 and 21, but lower than control levels on day 28. However, no difference in the number of blood vessels was observed between sides. Our results indicate that topical application of β-NGF promoted neurogenesis, and may modulate angiogenesis by promoting nerve regeneration in collagen bone substitute-filled defects. PMID:26330843

  14. Neuroprotective role of nerve growth factor in hypoxicischemic injury. From brain to skin.

    PubMed

    Chiaretti, Antonio; Falsini, Benedetto; Aloe, Luigi; Pierri, Filomena; Fantacci, Claudia; Riccardi, Riccardo

    2011-06-01

    Hypoxic-ischemic injuries (HII) of the brain, optic pathways, and skin are frequently associated with poor neurological and clinical outcome. Unfortunately, no new therapeutic approaches have been proposed for these conditions. Recently, experimental and clinical studies showed that nerve growth factor (NGF) can improve neurological deficits, visual loss and skin damage after HII. Based on these studies, we report the effects of NGF administration in different lesions of the brain, optic pathways and skin. 2.5S NGF purified and lyophilized from male mouse submaxillary glands was utilized for the treatment. NGF administration was started in absence of recovery after conventional and standardized treatment. One mg NGF was administered via the external catheter into the brain, by drop administration in the eye, and by subcutaneous administration in the skin. We treated 4 patients: 2 children with hypoxic-ischemic brain damage, an adult patient with an optic glioma-induced visual loss and a child with a severe crush syndrome of the lower left limb. After NGF treatment, we observed an amelioration of both neurological and electrophysiological function of the brain, a subjective and objective improvement of visual function, and a gradual improvement of ischemic skin lesion. No side effects were related to NGF treatment in all patients studied. Our observation shows that NGF administration may be an effective and safe adjunct therapy in patients with severe HII. The beneficial and prolonged effect on nerve function suggests a neuroprotective mechanism exerted by NGF on the residual viable neurological pathways of these patients. PMID:21702000

  15. Growth-associated protein 43 in differentiating peripheral nerve sheath tumors from other non-neural spindle cell neoplasms.

    PubMed

    Chen, Wei-Shen; Chen, Pei-Ling; Lu, Dongsi; Lind, Anne C; Dehner, Louis P

    2014-02-01

    The malignant peripheral nerve sheath tumor is a relatively uncommon type of soft tissue sarcoma arising from a peripheral nerve or extraneural soft tissues and showing nerve sheath differentiation. The diagnosis of malignant peripheral nerve sheath tumor is one of the most challenging tasks in surgical pathology because of its uncommon type (5-10% soft tissue sarcomas), morphologic resemblance to other spindle cell neoplasms and lack of sensitive and specific immunohistochemical markers. The pathologic diagnosis is more straightforward in the clinical setting of neurofibromatosis-1, but problems are mainly centered on the non-neurofibromatosis-1 malignant peripheral nerve sheath tumors. To date, S100 protein is the most widely applied marker in the case of a suspected malignant peripheral nerve sheath tumor, yet its suboptimal sensitivity and its expression in other spindle cell neoplasms, including spindle cell melanoma, clear-cell sarcoma, leiomyosarcoma and monophasic synovial sarcoma, add to the diagnostic conundrum. Growth-associated protein 43 (GAP43), a membrane-associated phosphoprotein expressed in neuronal growth cones and Schwann cell precursors during neural development and axonal regeneration, was applied to a set of nerve sheath and non-nerve sheath spindle cell neoplasms. The findings in this study indicate that GAP43 is expressed in malignant peripheral nerve sheath tumors (n=18/21; 86%) and demonstrates a sensitivity superior to S100 protein (n=13/21; 62%). GAP43 is also positive in neurofibromas (n=17/18; 94%), schwannomas (n=11/12; 92%) and desmoplastic melanomas (n=7/10; 70%). In contrast, it is negative in the non-desmoplastic spindle cell melanomas (n=20/22; 91%). Of the other non-neural soft tissue sarcomas, GAP43 is non-reactive in most leiomyosarcomas (n=14/16; 88%) and clear-cell sarcomas (n=8/8), and only focally positive in monophasic synovial sarcomas (n=3/7; 43%). GAP43 is seemingly a highly sensitive marker for peripheral nerve

  16. A Cell Line Producing Recombinant Nerve Growth Factor Evokes Growth Responses in Intrinsic and Grafted Central Cholinergic Neurons

    NASA Astrophysics Data System (ADS)

    Ernfors, Patrik; Ebendal, Ted; Olson, Lars; Mouton, Peter; Stromberg, Ingrid; Persson, Hakan

    1989-06-01

    The rat β nerve growth factor (NGF) gene was inserted into a mammalian expression vector and cotransfected with a plasmid conferring resistance to neomycin into mouse 3T3 fibroblasts. From this transfection a stable cell line was selected that contains several hundred copies of the rat NGF gene and produces excess levels of recombinant NGF. Such genetically modified cells were implanted into the rat brain as a probe for in vivo effects of NGF on central nervous system neurons. In a model of the cortical cholinergic deficits in Alzheimer disease, we demonstrate a marked increase in the survival of, and fiber outgrowth from, grafts of fetal basal forebrain cholinergic neurons, as well as stimulation of fiber formation by intact adult intrinsic cholinergic circuits in the cerebral cortex. Adult cholinergic interneurons in intact striatum also sprout vigorously toward implanted fibroblasts. Our results suggest that this model has implications for future treatment of neurodegenerative diseases.

  17. Nerve growth factor: a neurotrophin with activity on cells of the immune system.

    PubMed

    Aloe, L; Simone, M D; Properzi, F

    Numerous studies published in the last two decades provide evidence that nerve growth factor (NGF), a polypeptide originally discovered because of its neurotrophic activity, acts on a variety of cells of the immune system, including mast cells, eosinophils, and B and T lymphocytes. NGF has been shown to increase during inflammatory responses, autoimmune disorders, parasitic infections, and allergic diseases. Moreover, stress, which is characterized also by activation of a variety of immune cells, causes a significant increase in basal plasma NGF levels. Recently published studies reveal that hematopoietic progenitor cells seem to be able to produce and/or respond to NGF. We report these data and discuss the hypothesis of the possible implication of NGF on the functional activities of immune cells. PMID:10383121

  18. Measuring nerve growth factor in saliva by immunoassay: A cautionary note.

    PubMed

    Matin, Marla J; Li, Daming; Peterson, Jon; Taylor, Marcus K; Laurent, Heidemarie K; Lucas, Todd; Granger, Steve J; Granger, Douglas A; Granger, Steve W

    2016-01-01

    Nerve growth factor (NGF), a neurotrophin, modulates a diverse set of physiologic processes in the nervous, immune, and endocrine systems. Studies suggest that NGF can be measured in saliva (sNGF). Historically, the method for measuring sNGF involves the off-label use of an enzyme immunoassay designed for use with cell-culture supernatants/tissue extracts (Nam et al., 2007; Ruhl et al., 2004). In a series of experiments we reveal this measurement strategy is subject to non-specific interference by constituents present in oral fluids. We conclude that the measurement of sNGF by this assay is not optimal for use with oral fluid specimens. PMID:26519777

  19. Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance

    PubMed Central

    Turney, Stephen G.; Ahmed, Mostafa; Chandrasekar, Indra; Wysolmerski, Robert B.; Goeckeler, Zoe M.; Rioux, Robert M.; Whitesides, George M.; Bridgman, Paul C.

    2016-01-01

    Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion–cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. PMID:26631553

  20. Nerve growth factor partially recovers inflamed skin from stress-induced worsening in allergic inflammation.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Spatz, Katharina; Daniltchenko, Maria; Joachim, Ricarda; Gimenez-Rivera, Andrey; Hendrix, Sven; Botchkarev, Vladimir A; Brandner, Johanna M; Klapp, Burghard F

    2011-03-01

    Neuroimmune dysregulation characterizes atopic disease, but its nature and clinical impact remain ill-defined. Induced by stress, the neurotrophin nerve growth factor (NGF) may worsen cutaneous inflammation. We therefore studied the role of NGF in the cutaneous stress response in a mouse model for atopic dermatitis-like allergic dermatitis (AlD). Combining several methods, we found that stress increased cutaneous but not serum or hypothalamic NGF in telogen mice. Microarray analysis showed increased mRNAs of inflammatory and growth factors associated with NGF in the skin. In stress-worsened AlD, NGF-neutralizing antibodies markedly reduced epidermal thickening together with NGF, neurotrophin receptor (tyrosine kinase A and p75 neurotrophin receptor), and transforming growth factor-β expression by keratinocytes but did not alter transepidermal water loss. Moreover, NGF expression by mast cells was reduced; this corresponded to reduced cutaneous tumor necrosis factor-α (TNF-α) mRNA levels but not to changes in mast cell degranulation or in the T helper type 1 (Th1)/Th2 cytokine balance. Also, eosinophils expressed TNF receptor type 2, and we observed reduced eosinophil infiltration after treatment with NGF-neutralizing antibodies. We thus conclude that NGF acts as a local stress mediator in perceived stress and allergy and that increased NGF message contributes to worsening of cutaneous inflammation mainly by enhancing epidermal hyperplasia, pro-allergic cytokine induction, and allergy-characteristic cellular infiltration. PMID:21085186

  1. Effect of an Adipose-Derived Stem Cell and Nerve Growth Factor-Incorporated Hydrogel on Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury

    PubMed Central

    Kim, In Gul; Piao, Shuyu; Lee, Ji Young; Hong, Sung Hoo; Hwang, Tae-Kon; Kim, Sae Woong; Kim, Choung Soo; Ra, Jeong Chan; Noh, Insup

    2013-01-01

    Postprostatectomy erectile dysfunction (ED) is the major problem for patients with clinically localized prostate cancer. Recently, gene and stem cell-based therapy of the corpus cavernosum has been attempted for postprostatectomy ED, but those therapies are limited by rapid blood flow and disruption of the normal architecture of the corpus cavernosum. In this study, we attempted to regenerate the damaged cavernous nerve (CN), which is the main cause of ED. We investigated the effectiveness of human adipose-derived stem cell (hADSC) and nerve growth factor-incorporated hyaluronic acid-based hydrogel (NGF-hydrogel) application on the CN in a rat model of bilateral cavernous nerve crush injury. Four weeks after the operation, erectile function was assessed by detecting the intracavernous pressure (ICP)/arterial pressure level by CN electrostimulation. The ICP was significantly increased by application of hADSC with NGF-hydrogel compared to the other experimental groups. CN and penile tissue were collected for histological examination. PKH-26 labeled hADSC colocalized with beta III tubulin were shown in CN tissue sections. hADSC/NGF-hydrogel treatment prevented smooth muscle atrophy in the corpus cavernosum. In addition, the hADSC/NGF-hydrogel group showed increased endothelial nitric oxide synthase protein expression. This study suggests that application of hADSCs with NGF-hydrogel on the CN might be a promising treatment for postprostatectomy ED. PMID:22834730

  2. Nerve Growth Factor Receptor TrkA Is Expressed by Horizontal and Amacrine Cells During Chicken Retinal Development

    PubMed Central

    KARLSSON, MIRIAM; CLARY, DOUGLAS O.; LEFCORT, FRANCES B.; REICHARDT, LOUIS F.; KARTEN, HARVEY J.; HALLBÖÖK, FINN

    2009-01-01

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

  3. [NERVE GROWTH FACTOR IN THE URINE OF PATIENTS WITH IDIOPATHIC DETRUSOR OVERACTIVITY AND OVERACTIVE BLADDER WITHOUT DETRUSOR OVERACTIVITY].

    PubMed

    Krivoborodov, G G; Kolesanova, E F; Tur, E I; Efremov, N S

    2015-01-01

    The purpose was to determine the concentration of the neurotrophin nerve growth factor in urine to assess its possible role as a marker in the diagnosis of various forms of overactive bladder. The study included patients with urinary frequency and urgency: 21 patients with idiopathic detrusor overactivity, 18--with overactive bladder without detrusor overactivity and 11 healthy volunteers (control group). The level of nerve growth factor in the urine was determined in all participants of the study by the enzyme immunoassay (ELISA). In the control group the average ratio of nerve growth factor level to the level of urine creatinine was 0.2 ± 0.06, in patients with overactive bladder without detrusor overactivity -0.33 ± 0.06 (p > 0.05). In patients with idiopathic detrusor overactivity the rate was significantly higher and amounted to 6.04 ± 0.9 (p < 0.05). Therefore, measurement of the concentration of nerve growth factor in the urine may be used for differential diagnosis of the presence or absence of detrusor overactivity in patients with overactive bladder. PMID:26390554

  4. Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities in painful neuropathy of type 2 diabetes

    PubMed Central

    Cheng, Hsinlin T.; Dauch, Jacqueline R.; Hayes, John M.; Yanik, Brandon M.; Feldman, Eva L

    2011-01-01

    Painful diabetic neuropathy (PDN) is a common, yet devastating complication of type 2 diabetes. At this time, there is no objective test for diagnosing PDN. In the current study, we measured the peptidergic intraepidermal nerve fiber densities (IENFD) from hind paws of the db/db mouse, an animal model for type 2 diabetes, during the period of mechanical allodynia from 6–12 wk of age. Intraepidermal nerve fibers (IENF) of the hind footpads were identified by protein gene product (PGP) 9.5 immunohistochemistry. The peptidergic IENF were determined by double immunofluorescence using anti-PGP9.5 and antibodies against tropomyosin-receptor-kinase (Trk) A. We observed a significant increase in PGP9.5-positive IENFD at 8 and 10 wk of age. Similarly, Trk A-positive peptidergic IENF, which also express substance P and calcitonin gene related peptide in db/db mice, were observed to be elevated from 1.5 to 2 fold over controls. This upregulation ended at 16 wk of age, in accordance with the reduction of mechanical allodynia. Anti-NGF treatment significantly inhibited the upregulation of peptidergic IENFD during the period of mechanical allodynia, suggesting increased neurotrophism may mediate this phenomenon. In addition, SB203580, an inhibitor of p38, blocked the increase in peptidergic IENFD in db/db mice. The current results suggest peptidergic IENFD could be a potential diagnostic indicator for PDN in type 2 diabetes. Furthermore, the inhibition of NGF-p38 signaling could be a potential therapeutic strategy for treating this painful condition. PMID:21872660

  5. Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons

    SciTech Connect

    Richardson, P.M.; Riopelle, R.J.

    1984-07-01

    To investigate the distribution of nerve growth factor (NGF) receptors on peripheral and central axons, (/sup 125/I)NGF was injected into the sciatic nerve or spinal cord of adult rats. Accumulation of (/sup 125/I)NGF in lumbar dorsal root ganglia was monitored by gamma emission counting and radioautography. (/sup 125/I)NGF, injected endoneurially in small quantities, was taken into sensory axons by a saturable process and was transported retrogradely to their cell bodies at a maximal rate of 2.5 to 7.5 mm/hr. Because very little (/sup 125/I)NGF reached peripheral terminals, the results were interpreted to indicate that receptors for NGF are present on nonterminal segments of sensory axons. The specificity and high affinity of NGF uptake were illustrated by observations that negligible amounts of gamma activity accumulated in lumbar dorsal root ganglia after comparable intraneural injection of (/sup 125/I) cytochrome C or (/sup 125/I)oxidized NGF. Similar techniques were used to demonstrate avid internalization and retrograde transport of (/sup 125/I)NGF by intraspinal axons arising from dorsal root ganglia. Following injection of (/sup 125/I)NGF into lumbar or cervical regions of the spinal cord, neuronal perikarya were clearly labeled in radioautographs of lumbar dorsal root ganglia. Sites for NGF uptake on primary sensory neurons in the adult rat are not restricted to peripheral axon terminals but are extensively distributed along both peripheral and central axons. Receptors on axons provide a mechanism whereby NGF supplied by glia could influence neuronal maintenance or axonal regeneration.

  6. Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212)

    SciTech Connect

    Tron, V.A.; Coughlin, M.D.; Jang, D.E.; Stanisz, J.; Sauder, D.N. )

    1990-04-01

    Nerve growth factor (NGF) is a polypeptide that is required for normal development and maintenance of the sympathetic and sensory nervous systems. Skin has been shown to contain relatively high amounts of NGF, which is in keeping with the finding that the quantity of NGF in a tissue is proportional to the extent of sympathetic innervation of that organ. Since the keratinocyte, a major cellular constituent of the skin, is known to produce other growth factors and cytokines, our experiments were designed to determine whether keratinocytes are a source of NGF. Keratinocyte-conditioned media from the keratinocyte cell line PAM 212 contained NGF-like activity, approximately 2-3 ng/ml, as detected by the neurite outgrowth assay. Freshly isolated BALB/c keratinocytes contained approximately 0.1 ng/ml. Using a cDNA probe directed against NGF, we demonstrated the presence of a 1.3-kb NGF mRNA in both PAM 212 and BALB/c keratinocytes. Since ultraviolet radiation (UV) is a potentially important modulating factor for cytokines in skin, we examined the effect of UV on NGF mRNA expression. Although UV initially inhibited the expression of keratinocyte NGF mRNA (4 h), by 24 h an induction of NGF mRNA was seen. The NGF signal could also be induced by phorbol esters. Thus, keratinocytes synthesize and express NGF, and its expression is modulated by UVB and phorbol esters.

  7. Structural gene for beta-nerve growth factor not defective in familial dysautonomia.

    PubMed Central

    Breakefield, X O; Orloff, G; Castiglione, C; Coussens, L; Axelrod, F B; Ullrich, A

    1984-01-01

    The developmental loss of neurons in sympathetic, sensory, and some parasympathetic ganglia in familial dysautonomia suggests an inherited defect in the action of beta-nerve growth factor (beta-NGF). The role of this growth factor in dysautonomia has been difficult to resolve as there is no known source of authentic human beta-NGF. The availability of a cloned DNA probe for the human beta-NGF gene has allowed identification of some copies of the gene (alleles) in six affected families. Alleles differ in the length of restriction endonuclease fragments that hybridize to DNA probes for the gene. In two families, affected children did not inherit the same two alleles at the beta-NGF locus. Since this disease is transmitted in an autosomal recessive manner, affected children must share the same alleles at the locus causing the disease. This analysis excludes the beta-NGF gene region as the cause of this neurologic disease but does not eliminate other genes involved in beta-NGF action, such as those coding for processing enzymes, receptors, or other subunits of the NGF complex. Images PMID:6330750

  8. The role of nerve growth factor in the prophylaxis and treatment of diabetic foot ulcers

    PubMed Central

    Tiaka, Elisavet K; Papanas, Nikolaos; Manolakis, Anastassios C; Maltezos, Efstratios

    2011-01-01

    Diabetic foot ulcers are still particularly difficult to heal. Therefore, preventing and therapeutic adjuncts are increasingly being explored. Nerve growth factor (NGF) is a promising agent exhibiting beneficial actions on both diabetic peripheral neuropathy, one of the main causes of foot ulcers, and on ulcer healing. Indeed, preclinical research in animal models of diabetes has revealed the trophic effect of NGF on small C-fibres, while phase 2 human trials have provided evidence for a favourable effect on sensory neuropathy. However, the results of a phase 3 trial were moderate and, therefore, not enough to encourage widespread use of NGF in the treatment of diabetic neuropathy. Available literature on the role of NGF on diabetic wound healing is sparse but encouraging. Exogenous supplementation of NGF or the use of alternative techniques to increase its endogenous expression could emerge as a protective and therapeutic modality for diabetic foot ulcers in addition to standard treatment and other growth factors. The present review provides an outlook on the role of NGF in the prophylaxis and treatment of diabetic foot ulcers. PMID:22928161

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

    PubMed

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

    2013-12-01

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

  10. Membrane proteins of the nerve growth cone and their developmental regulation

    SciTech Connect

    Simkowitz, P.; Ellis, L.; Pfenninger, K.H.

    1989-03-01

    The membrane polypeptides of growth cone fragments (growth cone particles, GCPs) isolated from fetal rat brain by subcellular fractionation have been analyzed in further detail. The major polypeptides of salt-washed GCP membranes detected by 1-dimensional gel electrophoresis resolve in 2-dimensional gels as a spot of 52 kDa that comigrates with beta-tubulin and reacts with anti-beta-tubulin; a 46 kDa, pl 4.3, polypeptide (pp46) that has no equivalent in the soluble fraction and is identical to one of the GCP's major phosphoproteins and to GAP43; a spot of 42 kDa that comigrates with actin; and a species of 34 kDa (p34) without soluble equivalent. The prominent 38 kDa doublet identified in 1-dimensional gels is difficult to resolve in 2-dimensional gels. The major phosphoproteins pp80ac, pp46, and pp40, as well as p34 partition into the oil phase of Triton X-114 extracts, suggesting that they are integral membrane proteins, at least in our experimental conditions. The properties of pp46 reported here are in conflict with the highly hydrophilic amino acid sequence predicted for GAP43/B50/F1. Growth-cone and presynaptic membrane proteins are compared as follows. After eye injection of 35S-methionine, GCPs and synaptosomes are isolated from the target areas of optic nerve of fetal and adult rats, respectively. Polypeptides are separated by 1- and 2-dimensional gel electrophoresis and the radiolabeled species identified fluorographically. The comparison of labeled GCP and synaptosome polypeptides shows that all 5 major Coomassie blue-stained polypeptides of GCP membranes (52, 46, 42, 38, 34 kDa) are intensely labeled after eye injection. However, in synaptosomes, these polypeptides are weakly labeled if at all; instead, an intensely labeled polypeptide of 28 kDa, and several additional species not seen in GCPs, have appeared.

  11. Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

    PubMed Central

    Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

    2016-01-01

    IMPORTANCE Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and lacks effective disease modifying therapies. In 2001 we initiated a clinical trial of Nerve Growth Factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in AD patients. We present post-mortem findings in 10 subjects with survival times ranging from 1 to 10 years post-treatment. OBJECTIVE To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND PARTICIPANTS 10 patients with early AD underwent NGF gene therapy using either ex vivo or in vivo gene transfer. The brains of all eight patients in the first Phase 1 ex vivo trial and two patients in a subsequent Phase 1 in vivo trial were examined. MAIN OUTCOME MEASURES Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In two cases, NGF protein levels were measured by ELISA. RESULTS Degenerating neurons in the AD brain respond to NGF. All patients exhibited a trophic response to NGF, in the form of axonal sprouting toward the NGF source. Comparing treated and non-treated sides of the brain in three patients that underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P>0.05). Activation of cellular signaling and functional markers were present in two patients that underwent AAV2-mediated NGF gene transfer. Neurons exhibiting tau pathology as well as neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes with resulting activation of cell signaling. No adverse pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE These findings indicate that

  12. Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea

    PubMed Central

    Bu, Meng; Tang, Jingling; Wei, Yinghui; Sun, Yanhui; Wang, Xinyu; Wu, Linhua; Liu, Hongzhuo

    2015-01-01

    Purpose Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route. Methods A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously. Results Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane. Conclusion Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants. PMID:26604754

  13. Nerve growth factor preserves a critical motor period in rat striatum.

    PubMed

    Wolansky, M J; Paratcha, G C; Ibarra, G R; Azcurra, J M

    1999-01-01

    We previously found the occurrence of a critical motor period during rat postnatal development where circling training starting the 7-day schedule at 30 days-but not before or after-induces a lifetime drop in the binding to cholinergic muscarinic receptors (mAChRs) in striatum. Here, we studied whether nerve growth factor (NGF) participates in this restricted period of muscarinic sensitivity. For this purpose, we administered mouse salival gland 2.5S NGF (1.4 or 0.4 microg/day, infused by means of ALZA minipumps) by intrastriatal unilateral route between days 25 and 39, and then trained rats starting at 40 days. Under these conditions, NGF induced a long-term reduction in the striatal [3H] quinuclidilbenzylate (QNB) binding sites despite the fact that motor training was carried out beyond the natural critical period. Thus, at day 70, measurement of specific QNB binding in infused striata of trained rats showed decreases of 42% (p < .0004) and 33% (p < .02) after administration of the higher and lower NGF doses, respectively, with respect to trained rats treated with cytochrome C, for control. Noncannulated striata of the NGF-treated rats also showed a decrease in QNB binding sites (44%; p < .0001) only at the higher infusion rate. This effect was not found in the respective control groups. Our observations show that NGF modulates the critical period in which activity-dependent mAChR setting takes place during rat striatal maturation. PMID:10027568

  14. The multiple life of nerve growth factor: tribute to rita levi-montalcini (1909-2012).

    PubMed

    Aloe, Luigi; Chaldakov, George N

    2013-03-01

    At the end of the 19(th) century, it was envisaged by Santiago Ramon y Cajal, but not, proven, that life at the neuronal level requires trophic support. The proof was obtained in the early 1950's by work initiated by Rita Levi-Montalcini (RLM) discovering the nerve growth factor (NGF). Today, NGF and its relatives, collectively designated neurotrophins, are well recognized as mediators of multiple biological phenomena in health and disease, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other neurotrophins are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, from Alzheimer's and other neurodegenerative diseases to atherosclerosis and other cardiometabolic diseases. Recent studies demonstrated the therapeutic potentials of NGF in these diseases, including ocular and cutaneous diseases. Furthermore, NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, melanoma, and urinary bladder syndromes. Altogether, NGF's multiple potential in health and disease is briefly described here. PMID:25207059

  15. Structural and functional insights into lipid-bound nerve growth factors.

    PubMed

    Tong, Qiong; Wang, Feng; Zhou, Hong-Zhe; Sun, Han-Li; Song, Hui; Shu, Yu-Yan; Gong, Yong; Zhang, Wen-Ting; Cai, Tan-Xi; Yang, Fu-Quan; Tang, Jie; Jiang, Tao

    2012-09-01

    Nerve growth factor (NGF) is a dimeric molecule that modulates the survival, proliferation, and differentiation of nervous cells and is also known to act on cells of the immune system and endocrine system. NGFs extracted from mouse submaxillary gland and cobra venom have different immunological behaviors, yet the underlying mechanism remains unclear. Here we report the crystal structure of the NGF purified from Chinese cobra Naja naja atra (cNGF), which unexpectedly reveals a 2-tailed lipid molecule that is embedded between the two protomers of the NGF homodimer. In addition, crystallographic analysis indicated that the purified mouse NGF(mNGF) is free from lipid but can bind lysophosphatidylserine (lyso-PS) in the same pocket as cNGF. Bioassays indicated that the binding of lipid molecules to cNGF and mNGF are essential for their mast cell activation activity and abates their p75(NTR) binding capacity. Taken together, these results suggest a new mechanism for the regulation of the function of NGF. PMID:22649032

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

    PubMed

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

    2015-01-01

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

  17. The trk Tyrosine Protein Kinase Mediates the Mitogenic Properties of Nerve Growth Factor and Neurotrophin-3

    PubMed Central

    Cordon-Cardo, Carlos; Tapley, Peter; Jing, Shuqian; Nanduri, Venkata; O’Rourke, Edward; Lamballe, Fabienne; Kovary, Karla; Klein, Rüdiger; Jones, Kevin R.; Reichardt, Louis F.; Barbacid, Mariano

    2009-01-01

    Summary The product of the trk proto-oncogene encodes a receptor for nerve growth factor (NGF). Here we show that NGF is a powerful mitogen that can induce resting NIH 3T3 cells to enter S phase, grow in semisolid medium, and become morphologically transformed. These mitogenic effects are absolutely dependent on expression of gp140trk receptors, but do not require the presence of the previously described low affinity NGF receptor. gp140trk also serves as a receptor for the related factor neurotrophin-3 (NT-3), but not for brain-derived neurotrophic factor. Both NGF and NT-3 induce the rapid phosphorylation of gp140trk receptors and the transient expression of c-Fos proteins. However, NT-3 appears to elicit more limited mitogenic responses than NGF. These results indicate that the product of the trk proto-oncogene is sufficient to mediate signal transduction processes induced by NGF and NT-3, at least in proliferating cells. PMID:1649007

  18. Treatment of PC12 cells with nerve growth factor increases iron uptake.

    PubMed Central

    Mwanjewe, J; Hui, B K; Coughlin, M D; Grover, A K

    2001-01-01

    Phaeochromocytoma PC12 cells treated with nerve growth factor (NGF) differentiate into a neuronal phenotype. Here we compare the uptake of transferrin-bound and non-transferrin-bound iron in NGF-treated (neuronal phenotype) and control (proliferating) PC12 cells. The non-transferrin-bound iron uptake was greater in the NGF-treated cells than in the control, independently of the uptake time, the iron-chelating agents used, the oxidation state of iron (Fe(2+) or Fe(3+)) and the iron concentration tested. The NGF-treated cells expressed L-type and N-type voltage-operated Ca(2+) channels. Nitrendipine (an L-type inhibitor) and possibly omega-conotoxin (an N-type inhibitor) inhibited the iron uptake by 20%. Thapsigargin inhibits the endoplasmic reticulum Ca(2+) pump and allowed Mn(2+) entry into cells. Preincubating PC12 cells with thapsigargin increased the iron uptake. The rate of transferrin-bound iron uptake was less than 1% of the non-transferrin-bound iron uptake and the maximum transferrin-bound iron uptake was also very low. We conclude that an increase in the iron uptake by multiple pathways accompanies the transition of PC12 cells from the proliferating to the neuronal phenotype. PMID:11463361

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

    SciTech Connect

    Kasaian, M.T.

    1987-01-01

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

  20. Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

    PubMed Central

    Yang, Xiao-Qing; Xu, Yun-Fei; Guo, Sen; Liu, Yi; Ning, Shang-Lei; Lu, Xiao-Fei; Yang, Hui; Chen, Yu-Xin

    2014-01-01

    AIM: To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase (NGF-TrkA) signaling pathway and prognosis in intrahepatic cholangiocarcinoma (IHCC). METHODS: NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry. Correlations between NGF-TrkA expression and clinicopathological features were analyzed by χ2 test. Moreover, we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis. With experiments in vitro, we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-β stimulation. RESULTS: We found that NGF and TrkA expression was significantly related with differentiation (P = 0.024) and intraneural invasion (P = 0.003), respectively. Additionally, double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC (P = 0.003). Moreover, we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion. CONCLUSION: NGF-TrkA double higher expression is an independent prognostic factor in IHCC. NGF-TrkA pathway can promote IHCC progression, indicating that NGF-TrkA may become a potential drug target. PMID:24744599

  1. Serum brain-derived neurotrophic factor and nerve growth factor decreased in chronic ketamine abusers

    PubMed Central

    Ke, Xiaoyin; Ding, Yi; Xu, Ke; He, Hongbo; Zhang, Minling; Wang, Daping; Deng, Xuefeng; Zhang, Xifan; Zhou, Chao; Liu, Yuping; Ning, Yuping; Fan, Ni

    2016-01-01

    Aims This study investigated the serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in a group of chronic ketamine abusers in comparison to healthy controls. The correlations between the serum BDNF, NGF level with the subjects’ demographic, pattern of ketamine use were also examined. Methods 93 subjects who met the criteria of ketamine dependence and 39 healthy subjects were recruited. Serum BDNF and NGF levels were assayed by enzyme-linked immunosorbent assay (ELISA). Psychopathological symptoms were assessed using Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Results Both serum levels of BDNF and NGF were significant lower in the ketamine users compared to the healthy control subjects (9.50 ± 6.68 versus 14.37 ± 6.07 ng/ml, p = 0.019 for BDNF; 1.93 ± 0.80 versus 2.60 ± 1.07 ng/ml, p = 0.011 for NGF). BDNF level was negatively associated with current frequency of ketamine use (r = −0.209, p = 0.045). Conclusions Both BDNF and NGF serum concentrations were significantly lower among chronic ketamine users than among health controls. PMID:25064020

  2. Developmentally Regulated Expression of the Nerve Growth Factor Receptor Gene in the Periphery and Brain

    NASA Astrophysics Data System (ADS)

    Buck, C. R.; Martinez, Humberto J.; Black, Ira B.; Chao, Moses V.

    1987-05-01

    Nerve growth factor (NGF) regulates development and maintenance of function of peripheral sympathetic and sensory neurons. A potential role for the trophic factor in brain has been detected only recently. The ability of a cell to respond to NGF is due, in part, to expression of specific receptors on the cell surface. To study tissue-specific expression of the NGF receptor gene, we have used sensitive cRNA probes for detection of NGF receptor mRNA. Our studies indicate that the receptor gene is selectively and specifically expressed in sympathetic (superior cervical) and sensory (dorsal root) ganglia in the periphery, and by the septum-basal forebrain centrally, in the neonatal rat in vivo. Moreover, examination of tissues from neonatal and adult rats reveals a marked reduction in steady-state NGF receptor mRNA levels in sensory ganglia. In contrast, a 2- to 4-fold increase was observed in the basal forebrain and in the sympathetic ganglia over the same time period. Our observations suggest that NGF receptor mRNA expression is developmentally regulated in specific areas of the nervous system in a differential fashion.

  3. Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve Growth Factor-Mediated Signaling.

    PubMed

    Kim, Hyo Geun; Lim, Soonmin; Hong, Jongki; Kim, Ae-Jung; Oh, Myung Sook

    2016-02-01

    The flower bud of Zingiber mioga Roscoe, known as 'myoga' or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal-regulated kinases and cAMP response element-binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability. PMID:26563629

  4. The trk family of receptors mediates nerve growth factor and neurotrophin-3 effects in melanocytes.

    PubMed Central

    Yaar, M; Eller, M S; DiBenedetto, P; Reenstra, W R; Zhai, S; McQuaid, T; Archambault, M; Gilchrest, B A

    1994-01-01

    We have recently shown that (a) human melanocytes express the p75 nerve growth factor (NGF) receptor in vitro; (b) that melanocyte dendricity and migration, among other behaviors, are regulated at least in part by NGF; and (c) that cultured human epidermal keratinocytes produce NGF. We now report that melanocyte stimulation with phorbol 12-tetra decanoate 13-acetate (TPA), previously reported to induce p75 NGF receptor, also induces trk in melanocytes, and TPA effect is further potentiated by the presence of keratinocytes in culture. Moreover, trk in melanocytes becomes phosphorylated within minutes after NGF stimulation. As well, cultures of dermal fibroblasts express neurotrophin-3 (NT-3) mRNA; NT-3 mRNA levels in cultured fibroblasts are modulated by mitogenic stimulation, UV irradiation, and exposure to melanocyte-conditioned medium. Moreover, melanocytes constitutively express low levels of trk-C, and its expression is downregulated after TPA stimulation. NT-3 supplementation to cultured melanocytes maintained in Medium 199 alone prevents cell death. These combined data suggest that melanocyte behavior in human skin may be influenced by neurotrophic factors, possibly of keratinocyte and fibroblast origin, which act through high affinity receptors. Images PMID:7929831

  5. Nerve Growth Factor Regulates Neurolymphatic Remodeling during Corneal Inflammation and Resolution

    PubMed Central

    Fink, Darci M.; Connor, Alicia L.; Kelley, Philip M.; Steele, Maria M.; Hollingsworth, Michael A.; Tempero, Richard M.

    2014-01-01

    The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation–pain and swelling–by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that NGF-laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF-C. Adult human dermal lymphatic endothelial cells did not express canonical NGF receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors in the presence of NGF, although NGF treatment increased their migratory and tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a hierarchical relationship with NGF functioning upstream of the VEGF family members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together, these studies show that NGF stimulates lymphangiogenesis and that NGF may act as a pathogenic factor that negatively regulates the normal neural and lymphatic vascular remodeling events that accompany wound recovery. PMID:25383879

  6. Imbalance of the Nerve Growth Factor and Its Precursor: Implication in Diabetic Retinopathy

    PubMed Central

    Mohamed, Riyaz; El-Remessy, Azza B

    2015-01-01

    Diabetic retinopathy is the leading cause of blindness in working age in US and worldwide. Neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) are known to be essential for growth, differentiation and survival of neurons in the developing and mature retina. Nevertheless, a growing body of evidence supports an emerging role of neurotrophins in retinal diseases and in particular, diabetic retinopathy. Neurotrophins are initially synthesized in a pro-form and undergo proteolytic cleavage to produce the mature form that activates two distinctive receptors, the tyrosine kinase tropomycin receptor (Trk) and, to lesser extent, the common low affinity p75 neurotrophin receptor (p75NTR). Despite tight glycemic and metabolic control, many diabetic patients continue to experience progressive retinal damage. Understanding the molecular events involved in diabetic retinopathy is extremely important to identify novel therapeutic strategies to halt the disease progression. Diabetes induces imbalance in neurotrophins by increasing its proform, which is associated with upregulation of the p75NTR receptor in the retina. A growing body of evidence supports a link between the imbalance of pro-neurotrophins and early retinal inflammation, neuro-and microvascular degeneration. Therefore, examining changes in the levels of neurotrophins and its receptors might provide a therapeutically beneficial target to combat disease progression in diabetic patients. This commentary aims to highlight the impact of diabetes-impaired balance of neurotrophins and in particular, the NGF and its receptors; TrkA and p75NTR in the pathology of DR. PMID:26807305

  7. Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons.

    PubMed Central

    Winn, S R; Hammang, J P; Emerich, D F; Lee, A; Palmiter, R D; Baetge, E E

    1994-01-01

    Effective treatments for neurodegenerative disorders are limited by our inability to alter the progression of the diseases. A number of proteins have specific neuroprotective activities in vitro; however, the delivery of these factors into the central nervous system over the long term at therapeutic levels has been difficult to achieve. BHK cells engineered to express and release human nerve growth factor were encapsulated in an immunoisolation polymeric device and transplanted into both fimbria-fornix-lesioned rat brains and naive controls. In the lesioned rat brain, chronic delivery of human nerve growth factor by the encapsulated BHK cells provided nearly complete protection of axotomized medial septal cholinergic neurons. Human nerve growth factor continued to be released by encapsulated cells upon removal from the aspirative site after 3 weeks or from normal rat striatum after 3 and 6 months in vivo. Long-term encapsulated cell survival was confirmed by histologic analysis. This encapsulated xenogeneic system may provide therapeutically effective amounts of a number of neurotrophic factors, alone or in combination, to virtually any site within the body. Images PMID:8134395

  8. Effect of exercise on the expression of nerve growth factor in the spinal cord of rats with induced osteoarthritis.

    PubMed

    Park, Soo-Jin; Yong, Min-Sik; Na, Sang-Su

    2015-08-01

    [Purpose] We examined the impact of exercise on the expression pattern of nerve growth factor in the spinal cord of rats with induced osteoarthritis of the knee joint. [Subjects and Methods] To produce monosodium iodoacetate-induced arthritis, rats were administered 3 mg/50 µL monosodium iodoacetate through the interarticular space of the right knee. The animals were randomly divided into four groups: rats sacrificed 3 weeks after 0.9% saline solution injection (shame group, n = 10), rats sacrificed 3 weeks after monosodium iodoacetate injection (control group, n = 10), rats with 4 weeks rest from 3 weeks after monosodium iodoacetate injection (no exercise group, n = 10), and rats with 4 weeks treadmill training from 3 weeks after monosodium iodoacetate injection (exercise group, n = 10). Serial coronal sections of the lumbar spine were cut and processed for immunohistochemistry. [Results] The expression of nerve growth factor was significantly increased in the EG compared with the SG, CG, and NEG. [Conclusion] Increased nerve growth factor expression in the spinal cord due to exercise-induced stimulation can be effective in treating chronic pain. Such treatment will contribute not only to improving the joint function of patients with chronic pain but also their quality of life. PMID:26357438

  9. Carnosic acid, a component of rosemary (Rosmarinus officinalis L.), promotes synthesis of nerve growth factor in T98G human glioblastoma cells.

    PubMed

    Kosaka, Kunio; Yokoi, Toshio

    2003-11-01

    Nerve growth factor (NGF) is a factor vital for the growth and functional maintenance of nerve tissue. The authors found that a rosemary (Rosmarinus officinalis L.) extract enhanced the production of NGF in T98G human glioblastoma cells. Furthermore, the results indicated that carnosic acid and carnosol, which are major components of the rosemary extract, were able to promote markedly enhanced synthesis of NGF. PMID:14600414

  10. Expression of nerve growth factor and its receptors in the uterus of rabbits: functional involvement in prostaglandin synthesis.

    PubMed

    Maranesi, M; Parillo, F; Leonardi, L; Rebollar, P G; Alonso, B; Petrucci, L; Gobbetti, A; Boiti, C; Arruda-Alencar, J; Moura, A; Zerani, M

    2016-07-01

    The aim of the present study was to evaluate: (1) the presence of nerve growth factor (NGF), neurotrophic tyrosine kinase receptor 1 (NTRK1), and nerve growth factor receptor (NGFR) in the rabbit uterus; and (2) the in vitro effects of NGF on PGF2α and PGE2 synthesis and on the PGE2-9-ketoreductase (PGE2-9-K) activity by the rabbit uterus. Nerve growth factor, NTRK1, and NGFR were immunolocalized in the luminal and glandular epithelium and stroma cells of the endometrium. reverse transcriptase polymerase chain reaction indicated the presence of messenger RNA for NGF, NTRK1, and NGFR in the uterus. Nerve growth factor increased (P < 0.01) in vitro secretions of PGF2α and PGE2 but coincubation with either NTRK1 or oxide nitric synthase (NOS) inhibitors reduced (P < 0.01) PGF2α production and blocked (P < 0.01) PGE2 secretion. Prostaglandins releases were lower (P < 0.01) than control when uterine samples were treated with NGF plus cyclooxygenase inhibitor. However, addition of NGFR inhibitor reduced (P < 0.01) PGF2α secretion less efficiently than NTRK1 or NOS inhibitors but had no effect on PGE2 yield. Nerve growth factor increased (P < 0.01) the activity of PGE2-9-K, whereas coincubation with NTRK1 or NOS inhibitors abolished (P < 0.01) this increase in PGE2-9-K activity. However, cotreatment with either cyclooxygenase or NGFR inhibitors had no effect on PGE2-9-K activity. This is the first study to document the distribution of NGF/NTRK1 and NGFR systems and their effects on prostaglandin synthesis in the rabbit uterus. NGF/NTRK1 increases PGF2α and PGE2 productions by upregulating NOS and PGE2-9-K activities, whereas NGF/NGFR augments only PGF2α secretion, through an intracellular mechanism that is still unknown. PMID:26986844

  11. Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease.

    PubMed Central

    Mufson, E J; Kordower, J H

    1992-01-01

    Using a monoclonal antibody directed against the primate nerve growth factor (NGF) receptor, we examined the expression of NGF receptors within neuronal perikarya of normal adult human cerebral cortex (27-98 years old) and individuals with Alzheimer disease (AD). This expression of cortical NGF receptors was compared with that seen in other neurological diseases and normal human development as well as in young and aged nonhuman primates. NGF receptor-containing cortical neurons were not observed in young adults (less than 50 years old) and were observed only infrequently in non-demented elderly individuals (50-80 years old). In contrast, numerous NGF receptor-containing cortical neurons were seen in AD patients of all ages and in one 98-year-old nondemented patient. In advanced age and AD, numerous NGF receptor-positive neurons were located within laminae II-VI of temporal association cortices whereas only a few were seen in the subicular complex, entorhinal cortex, parahippocampal gyrus, and amygdaloid complex. These perikarya appeared healthy, with bipolar, fusiform, or multipolar morphologies and extended varicose dendritic arbors. These neurons failed to express neurofibrillary tangle-bearing material. In contrast to AD, NGF receptor-containing cortical neurons were not observed in Parkinson disease, Pick disease, or Shy-Drager syndrome. The NGF receptor-containing cortical neurons seen in advanced age and AD were similar in morphology to those observed in human fetal cortex. No NGF receptor-containing cortical neurons were observed in young or aged nonhuman primates. These findings suggest that neurons within the human cerebral cortex exhibit plasticity in their expression of NGF receptors in AD and extreme advanced aging. Images PMID:1309947

  12. Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans.

    PubMed

    Andersen, Helle; Arendt-Nielsen, Lars; Svensson, Peter; Danneskiold-Samsøe, Bente; Graven-Nielsen, Thomas

    2008-11-01

    Intramuscular injection of nerve growth factor (NGF) has been shown to induce long-term sensitisation and time-dependent hyperalgesia indicating potential involvement of both central and peripheral pain mechanisms. This double-blind placebo-controlled study was designed to describe the spatial distribution of muscle hyperalgesia over time (immediately after, 3 h, 1, 4, 7 and 21 days) after injecting NGF (5 mug) into the tibialis anterior (TA) muscle, to explore possibly involved central pain mechanisms and to investigate the effect of gender on development of hyperalgesia. Totally 20 healthy volunteers (10 men and 10 women) participated in the study. An isotonic saline injection into the contralateral TA muscle served as a control condition for the NGF injection. Pressure pain thresholds (PPT) were used to test for muscle hyperalgesia along the TA (seven sites) muscle at the extensor digitorum longus and at the web between 1st and 2nd metatarsal (central involvement). One day after the NGF/control injections, hypertonic saline (0.5 ml, 5.8%) was injected into the left and right TA to study the pain response to chemical stimulation of the hyperalgesic muscle tissue. Scores on a modified Likert scale were used to assess soreness during muscle function. An area of hyperalgesia was observed locally at the injected site 3 h after injection of NGF, which expanded both proximally and distally on day 1; this effect subsided on day 4. Decreased PPT was also found between 1st and 2nd metatarsal on day 1. Hypertonic saline evoked more pain in men when injected in the NGF treated TA compared to the control leg. Injection of NGF increased muscle soreness during muscle activity for 7 days. In this material there was no gender effect of NGF-induced muscle hyperalgesia. The expansion of muscle hyperalgesia to distant areas indicates that central mechanisms are involved. PMID:18813917

  13. Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor

    PubMed Central

    Song, Fengju; Zheng, Hong; Chen, Kexin; Zhang, Wei; Yang, Jilong

    2016-01-01

    Background Malignant peripheral nerve sheath tumors (MPNST) are rare, highly malignant, and poorly understood sarcomas. The often poor outcome of MPNST highlights the necessity of identifying prognostic predictors for this aggressive sarcoma. Here, we investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs. Results aCGH and bioinformatics analysis identified frequent amplification of the FGFR1 gene. FISH analysis revealed that 26.9% MPNST samples had amplification of FGFR1, with both focal and polysomy patterns observed. IHC identified that FGFR1 protein expression was positively correlated with FGFR1 gene amplification. High expression of FGFR1 protein was associated with better overall survival (OS) and was an independent prognostic predictor for OS of MPNST patients. Additionally, combined expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better OS. FGFR4 protein was expressed 82.3% of MPNST samples, and was associated with poor disease-free survival. Materials and Methods We performed microarray-based comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Medical University Cancer Institute and Hospital. Fluorescence in situ hybridization (FISH) was used to validate the gene amplification detected by aCGH analysis. Another cohort of 63 formalin-fixed paraffin-embedded MPNST samples (including 52 samples for FISH assay) was obtained to explore FGFR1, 2, 3, and 4 protein expression by immunohistochemical (IHC) analysis. Conclusions Our integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST. PMID:26993773

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

    NASA Astrophysics Data System (ADS)

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

    1982-02-01

    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.

  15. Cross Talk between Neuroregulatory Molecule and Monocyte: Nerve Growth Factor Activates the Inflammasome

    PubMed Central

    Datta-Mitra, Ananya; Kundu-Raychaudhuri, Smriti; Mitra, Anupam; Raychaudhuri, Siba P.

    2015-01-01

    Background Increasing evidence points to a role for the extra-neuronal nerve growth factor (NGF) in acquired immune responses. However, very little information is available about its role and underlying mechanism in innate immunity. The role of innate immunity in autoimmune diseases is becoming increasingly important. In this study, we explored the contribution of pleiotropic NGF in the innate immune response along with its underlying molecular mechanism with respect to IL-1β secretion. Methods Human monocytes, null and NLRP3 deficient THP-1 cell lines were used for this purpose. We determined the effect of NGF on secretion of IL-1β at the protein and mRNA levels. To determine the underlying molecular mechanism, the effect of NGF on NLRP1/NLRP3 inflammasomes and its downstream key protein, activated caspase-1, were evaluated by ELISA, immunoflorescence, flow cytometry, and real-time PCR. Results In human monocytes and null THP-1 cell line, NGF significantly upregulates IL-1β at protein and mRNA levels in a caspase-1 dependent manner through its receptor, TrkA. Furthermore, we observed that NGF induces caspase-1 activation through NLRP1/NLRP3 inflammasomes, and it is dependent on the master transcription factor, NF-κB. Conclusions To best of our knowledge, this is the first report shedding light on the mechanistic aspect of a neuroregulatory molecule, NGF, in innate immune response, and thus enriches our understanding regarding its pathogenic role in inflammation. These observations add further evidence in favor of anti-NGF therapy in autoimmune diseases and also unlock a new area of research about the role of NGF in IL-1β mediated diseases. PMID:25876154

  16. Lower Levels of Urinary Nerve Growth Factor Might Predict Recurrent Urinary Tract Infections in Women

    PubMed Central

    2016-01-01

    Purpose: To investigate the changes in urinary nerve growth factor (uNGF) levels after acute urinary tract infection (UTI) and to assess the role of uNGF in predicting UTI recurrence in women. Methods: Women with uncomplicated, symptomatic UTIs were enrolled. Cephalexin 500 mg (every 6 hours) was administered for 7–14 days to treat acute UTIs. Subsequently, the patients were randomized to receive either sulfamethoxazole/trimethoprim 800 mg/160 mg daily at bedtime, or celecoxib 200 mg daily for 3 months and were monitored for up to 12 months. NGF levels in the urine were determined at baseline, 1, 4, and 12 weeks after the initiation of prophylactic therapy, and were compared between women with first-time UTIs and recurrent UTIs, sulfamethoxazole/trimethoprim and celecoxib-treated women, and no UTI recurrence and UTI recurrence that occurred during the follow-up period. Twenty women free of UTIs served as controls. Results: A total of 139 women with UTI and 20 controls were enrolled in the study, which included 50 women with a first-time UTI and 89 women with recurrent UTIs. Thirty-seven women completed the study. Women with recurrent UTIs (n=23) had a trend of lower uNGF levels than women with first-time UTIs (n=14). During follow-up, 9 women had UTI recurrence. The serial uNGF levels in women with UTI recurrence were significantly lower than those in women who did not have UTI recurrence during the follow-up period. Conclusions: The lower levels of uNGF in women with recurrent UTI and the incidence of UTI recurrence during follow-up suggest that lower uNGF might reflect the defective innate immunity in women with recurrent UTI. PMID:27032555

  17. Nerve Growth Factor Is Regulated by Toll-Like Receptor 2 in Human Intervertebral Discs.

    PubMed

    Krock, Emerson; Currie, J Brooke; Weber, Michael H; Ouellet, Jean A; Stone, Laura S; Rosenzweig, Derek H; Haglund, Lisbet

    2016-02-12

    Nerve growth factor (NGF) contributes to the development of chronic pain associated with degenerative connective tissue pathologies, such as intervertebral disc degeneration and osteoarthritis. However, surprisingly little is known about the regulation of NGF in these conditions. Toll-like receptors (TLR) are pattern recognition receptors classically associated with innate immunity but more recently were found to be activated by endogenous alarmins such as fragmented extracellular matrix proteins found in degenerating discs or cartilage. In this study we investigated if TLR activation regulates NGF and which signaling mechanisms control this response in intervertebral discs. TLR2 agonists, TLR4 agonists, or IL-1β (control) treatment increased NGF, brain-derived neurotrophic factor (BDNF), and IL-1β gene expression in human disc cells isolated from healthy, pain-free organ donors. However, only TLR2 activation or IL-1β treatment increased NGF protein secretion. TLR2 activation increased p38, ERK1/2, and p65 activity and increased p65 translocation to the cell nucleus. JNK activity was not affected by TLR2 activation. Inhibition of NF-κB, and to a lesser extent p38, but not ERK1/2 activity, blocked TLR2-driven NGF up-regulation at both the transcript and protein levels. These results provide a novel mechanism of NGF regulation in the intervertebral disc and potentially other pathogenic connective tissues. TLR2 and NF-κB signaling are known to increase cytokines and proteases, which accelerate matrix degradation. Therefore, TLR2 or NF-κB inhibition may both attenuate chronic pain and slow the degenerative progress in vivo. PMID:26668319

  18. Noninflammatory upregulation of nerve growth factor underlies gastric hypersensitivity induced by neonatal colon inflammation.

    PubMed

    Li, Qingjie; Winston, John H; Sarna, Sushil K

    2016-02-01

    Gastric hypersensitivity is one of the key contributors to the postprandial symptoms of epigastric pain/discomfort, satiety, and fullness in functional dyspepsia patients. Epidemiological studies found that adverse early-life experiences are risk factors for the development of gastric hypersensitivity. Preclinical studies found that neonatal colon inflammation elevates plasma norepinephrine (NE), which upregulates expression of nerve growth factor (NGF) in the muscularis externa of the gastric fundus. Our goal was to investigate the cellular mechanisms by which NE upregulates the expression of NGF in gastric hypersensitive (GHS) rats, which were subjected previously to neonatal colon inflammation. Neonatal colon inflammation upregulated NGF protein, but not mRNA, in the gastric fundus of GHS rats. Western blotting showed upregulation of p110γ of phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), phosphoinositide-dependent kinase-1 (PDK1), pAKT(Ser473), and phosphorylated 4E-binding protein (p4E-BP1)(Thr70), suggesting AKT activation and enhanced NGF protein translation. AKT inhibitor MK-2206 blocked the upregulation of NGF in the fundus of GHS rats. Matrix metalloproteinase 9 (MMP-9), the major NGF-degrading protease, was suppressed, indicating that NGF degradation was impeded. Incubation of fundus muscularis externa with NE upregulated NGF by modulating the protein translation and degradation pathways. Yohimbine, an α2-adrenergic receptor antagonist, upregulated plasma NE and NGF expression by activating the protein translation and degradation pathways in naive rats. In contrast, a cocktail of adrenergic receptor antagonists suppressed the upregulation of NGF by blocking the activation of the protein translation and degradation pathways. Our findings provide evidence that the elevation of plasma NE induces NGF expression in the gastric fundus. PMID:26608656

  19. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.

    PubMed Central

    Bonini, S; Lambiase, A; Bonini, S; Angelucci, F; Magrini, L; Manni, L; Aloe, L

    1996-01-01

    Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma. Images Fig. 2 PMID:8855290

  20. Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

    PubMed

    De Santis, S; Pace, A; Bove, L; Cognetti, F; Properzi, F; Fiore, M; Triaca, V; Savarese, A; Simone, M D; Jandolo, B; Manzione, L; Aloe, L

    2000-01-01

    The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds. PMID:10656436

  1. Three important components in the regeneration of the cavernous nerve: brain-derived neurotrophic factor, vascular endothelial growth factor and the JAK/STAT signaling pathway.

    PubMed

    Zhang, Hai-Yang; Jin, Xun-Bo; Lue, Tom F

    2011-03-01

    Retroperitoneal operations, such as radical prostatectomy, often damage the cavernous nerve, resulting in a high incidence of erectile dysfunction. Although improved nerve-sparing techniques have reduced the incidence of nerve injury, and the administration of phosphodiesterase type 5 inhibitors has revolutionized the treatment of erectile dysfunction, this problem remains a considerable challenge. In recent years, scientists have focused on brain-derived neurotrophic factor and vascular endothelial growth factor in the treatment of cavernous nerve injury in rat models. Results showed that both compounds were capable of enhancing the regeneration of the cavernous nerve and that activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway played a major role in the process. PMID:21170078

  2. Nicotine Stimulates Nerve Growth Factor in Lung Fibroblasts through an NFκB-Dependent Mechanism

    PubMed Central

    Wongtrakool, Cherry; Grooms, Kora; Bijli, Kaiser M.; Crothers, Kristina; Fitzpatrick, Anne M.; Hart, C. Michael

    2014-01-01

    Rationale Airway hyperresponsiveness (AHR) is classically found in asthma, and persistent AHR is associated with poor asthma control. Although airway smooth muscle (ASM) cells play a critical pathophysiologic role in AHR, the paracrine contributions of surrounding cells such as fibroblasts to the contractile phenotype of ASM cells have not been examined fully. This study addresses the hypothesis that nicotine promotes a contractile ASM cell phenotype by stimulating fibroblasts to increase nerve growth factor (NGF) secretion into the environment. Methods Primary lung fibroblasts isolated from wild type and α7 nicotinic acetylcholine receptor (α7 nAChR) deficient mice were treated with nicotine (50 µg/ml) in vitro for 72 hours. NGF levels were measured in culture media and in bronchoalveolar lavage (BAL) fluid from asthmatic, smoking and non-smoking subjects by ELISA. The role of the NFκB pathway in nicotine-induced NGF expression was investigated by measuring NFκB nuclear translocation, transcriptional activity, chromatin immunoprecipitation assays, and si-p65 NFκB knockdown. The ability of nicotine to stimulate a fibroblast-mediated, contractile ASM cell phenotype was confirmed by examining expression of contractile proteins in ASM cells cultured with fibroblast-conditioned media or BAL fluid. Results NGF levels were elevated in the bronchoalveolar lavage fluid of nicotine-exposed mice, current smokers, and asthmatic children. Nicotine increased NGF secretion in lung fibroblasts in vitro in a dose-dependent manner and stimulated NFκB nuclear translocation, p65 binding to the NGF promoter, and NFκB transcriptional activity. These responses were attenuated in α7 nAChR deficient fibroblasts and in wild type fibroblasts following NFκB inhibition. Nicotine-treated, fibroblast-conditioned media increased expression of contractile proteins in ASM cells. Conclusion Nicotine stimulates NGF release by lung fibroblasts through α7 nAChR and NFκB dependent pathways

  3. Nerve Growth Factor Secretion From Pulp Fibroblasts is Modulated by Complement C5a Receptor and Implied in Neurite Outgrowth.

    PubMed

    Chmilewsky, Fanny; Ayaz, Warda; Appiah, James; About, Imad; Chung, Seung-Hyuk

    2016-01-01

    Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential. Previous studies demonstrated that the complement system, a major component of innate immunity and inflammation, is activated at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction of the active Complement C5a fragment with pulp progenitor cells. In this study, we further determined the role of the active fragment complement C5a receptor (C5aR) in dental nerve regeneration in regards to local secretion of nerve growth factor (NGF) upon carious injury. Using ELISA and AXIS co-culture systems, we demonstrate that C5aR is critically implicated in the modulation of NGF secretion by LTA-stimulated pulp fibroblasts. The NGF secretion by LTA-stimulated pulp fibroblasts, which is negatively regulated by C5aR activation, has a role in the control of the neurite outgrowth length in our axon regeneration analysis. Our data provide a scientific step forward that can guide development of future therapeutic tools for innovative and incipient interventions targeting the dentin-pulp regeneration process by linking the neurite outgrowth to human pulp fibroblast through complement system activation. PMID:27539194

  4. Expression of Nerve Growth Factor (NGF), TrkA, and p75NTR in Developing Human Fetal Teeth

    PubMed Central

    Mitsiadis, Thimios A.; Pagella, Pierfrancesco

    2016-01-01

    Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75NTR and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75NTR, and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75NTR expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75NTR in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75NTR, and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues. PMID:27536251

  5. Nerve Growth Factor Secretion From Pulp Fibroblasts is Modulated by Complement C5a Receptor and Implied in Neurite Outgrowth

    PubMed Central

    Chmilewsky, Fanny; Ayaz, Warda; Appiah, James; About, Imad; Chung, Seung-Hyuk

    2016-01-01

    Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential. Previous studies demonstrated that the complement system, a major component of innate immunity and inflammation, is activated at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction of the active Complement C5a fragment with pulp progenitor cells. In this study, we further determined the role of the active fragment complement C5a receptor (C5aR) in dental nerve regeneration in regards to local secretion of nerve growth factor (NGF) upon carious injury. Using ELISA and AXIS co-culture systems, we demonstrate that C5aR is critically implicated in the modulation of NGF secretion by LTA-stimulated pulp fibroblasts. The NGF secretion by LTA-stimulated pulp fibroblasts, which is negatively regulated by C5aR activation, has a role in the control of the neurite outgrowth length in our axon regeneration analysis. Our data provide a scientific step forward that can guide development of future therapeutic tools for innovative and incipient interventions targeting the dentin-pulp regeneration process by linking the neurite outgrowth to human pulp fibroblast through complement system activation. PMID:27539194

  6. A nerve growth factor peptide retards seizure development and inhibits neuronal sprouting in a rat model of epilepsy.

    PubMed Central

    Rashid, K; Van der Zee, C E; Ross, G M; Chapman, C A; Stanisz, J; Riopelle, R J; Racine, R J; Fahnestock, M

    1995-01-01

    Kindling, an animal model of epilepsy wherein seizures are induced by subcortical electrical stimulation, results in the upregulation of neurotrophin mRNA and protein in the adult rat forebrain and causes mossy fiber sprouting in the hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve growth factor domain that interferes with the binding of neurotrophins to their receptors resulted in significant retardation of kindling and inhibition of mossy fiber sprouting. These findings suggest a critical role for neurotrophins in both kindling and kindling-induced synaptic reorganization. Images Fig. 2 PMID:7568161

  7. Recombinant human nerve growth factor for clinical trials: protein expression, purification, stability and characterisation of binding to infusion pumps.

    PubMed

    Allen, S J; Robertson, A G; Tyler, S J; Wilcock, G K; Dawbarn, D

    2001-02-26

    Nerve growth factor (NGF) has been suggested to be of therapeutic benefit to patients with Alzheimer's disease. One of the early changes in this disease is a loss of cholinergic function within the brain, and NGF is able to rescue cholinergic neurons both in vitro and in vivo. We describe the production of recombinant human beta-NGF (rhNGF), using baculovirus infection of insect cells; its purification, formulation and subsequent stability for use in clinical trials. Tests were also carried out to monitor release of protein from infusion pumps and catheters for intracerebroventricular administration (icv). Initial problems with non-specific binding were overcome using a blocking formula. PMID:11245895

  8. Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue.

    PubMed

    Taurone, Samanta; Bianchi, Enrica; Attanasio, Giuseppe; Di Gioia, Cira; Ierinó, Rocco; Carubbi, Cecilia; Galli, Daniela; Pastore, Francesco Saverio; Giangaspero, Felice; Filipo, Roberto; Zanza, Christian; Artico, Marco

    2015-07-01

    Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular

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

    PubMed Central

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

    2009-01-01

    Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6) and the neurotrophin (NT) Nerve Growth Factor (NGF) for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold), regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold), growth differentiation factor 15 (GDF15; 80-fold), platelet-derived growth factor alpha (PDGFA; 69-fold), growth hormone releasing hormone (GHRH; 30-fold), adenylate cyclase activating polypeptide (PACAP; 20-fold) and hepatocyte growth factor (HGF; 5-fold). NGF recruits GDF15 (131-fold), transforming growth factor beta 1 (TGFB1; 101-fold) and brain-derived neurotrophic factor (BDNF; 89-fold). Both stimuli activate growth-associated protein 43 (GAP-43) indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold) and early growth response 1 (Egr1/Zif268; 3-fold) known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell adhesion, small

  10. Carnosine, nerve growth factor receptor and tyrosine hydroxylase expression during the ontogeny of the rat olfactory system.

    PubMed

    Biffo, S; Martí, E; Fasolo, A

    1992-01-01

    The localizations of carnosine, nerve growth factor (NGF) receptor and tyrosine hydroxylase (TH) were studied in the embryonic and postnatal rat olfactory bulb and epithelium by means of single- and double-immunostaining methods. Tyrosine hydroxylase ontogeny was also evaluated at the mRNA level by in situ hybridization. All these molecules were expressed in the olfactory bulb but with different developmental patterns and cellular localization: carnosine immunoreactivity is seen from embryonic day 17 in primary olfactory neurons scattered in the nasal cavity and in fibres projecting from them to the olfactory bulb. Nerve growth factor-receptor immunoreactivity associated with small glial-like cells is visible in some glomeruli starting from the second day of postnatal life. At postnatal day 10 NGF-receptor immunoreactivity is extended to all glomeruli. Periglomerular neurons expressing TH mRNA and protein are present prenatally and their number sharply increases during the early postnatal development. Double-staining methods show that TH and NGF-receptor immunoreactivity do not overlap in cell bodies and processes. In addition, NGF-receptor immunoreactivity is not colocalized with carnosine. These findings definitely exclude NGF-receptor expression in periglomerular and primary olfactory neurons, suggesting that at least part of NGF-receptor expression in the olfactory bulb is associated with glial cells. In addition, they provide the first immunohistochemical data on carnosine ontogeny and confirm at the mRNA level previous studies on the ontogeny of TH protein. PMID:1376608

  11. Ex Vivo Assay of Electrical Stimulation to Rat Sciatic Nerves: Cell Behaviors and Growth Factor Expression.

    PubMed

    Du, Zhiyong; Bondarenko, Olexandr; Wang, Dingkun; Rouabhia, Mahmoud; Zhang, Ze

    2016-06-01

    Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities. PMID:26516696

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

    PubMed

    Ni, Hsiao-Chiang; Tseng, Ting-Chen; Chen, Jeng-Rung; Hsu, Shan-Hui; Chiu, Ing-Ming

    2013-09-01

    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. PMID:23880639

  13. Controlled release of vascular endothelial growth factor using poly-lactic-co-glycolic acid microspheres: In vitro characterization and application in polycaprolactone fumarate nerve conduits

    PubMed Central

    Rui, Jing; Dadsetan, Mahrokh; Runge, M. Brett; Spinner, Robert J.; Yaszemski, Michael J.; Windebank, Anthony J.; Wang, Huan

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of VEGF encapsulating poly-lactic-co-glycolic acid (PLGA) microspheres and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16% of the microspheres with a diameter < 53 µm. VEGF content measured by ELISA indicated 93.79 ±10.64% encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6±8.25% within the first 24 hours, followed by consistent release of approximately 0.34% per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation confirming that VEGF retained its bioactivity through the 4-week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold, robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system. PMID:22019759

  14. An assessment of sympathetic function in isolated tissues from mice given nerve-growth-factor antiserum and 6-hydroxydopamine

    PubMed Central

    Hughes, I. E.; Kirk, Jennifer A.; Kneen, Barbara; Large, B. J.

    1973-01-01

    1. Experiments were done on isolated tissues from mice injected with 0·9% w/v NaCl solution (saline), 6-hydroxydopamine (6-OHDA), nerve-growth-factor antiserum (NGF-As) or a combination of these agents (NGF-As+6-OHDA). 2. Fluorescence histochemistry of vasa deferentia showed clear differences between each of the treatments but no such distinction was possible in cardiac ventricle or intestine. 3. Compared with controls, the chronotropic responses of atria to field stimulation were reduced by all three treatments in the order NGF-As<6-OHDAnerve stimulation was reduced in the NGF-As group, whilst preparations from the two groups given 6-OHDA usually gave a motor response which was blocked by atropine. 6. None of the treatments employed in these experiments caused complete sympathectomy although 6-OHDA alone or in combination with NGF-As produced a more pronounced effect than NGF-As alone and the relative ineffectiveness of the latter is discussed. The implications of the motor response after 6-OHDA in ileum when the nerves were stimulated is considered in the light of the cholinergic link hypothesis. PMID:4723797

  15. Correlation between nerve growth factor and tissue expression of IL-17 in leprosy.

    PubMed

    Aarão, Tinara Leila de Sousa; de Sousa, Jorge Rodrigues; Botelho, Beatriz Santos; Fuzii, Hellen Thais; Quaresma, Juarez Antonio Simões

    2016-01-01

    Leprosy is a serious public health problem in peripheral and developing countries. Leprosy is a chronic infectious-contagious disease caused by the intracellular, bacillus Mycobacterium leprae, which causes tissue damage and demyelination of peripheral nerves. Recent studies have demonstrated the participation of new subtype's cytokines profile in the inflammatory response of leprosy. Since nerve functions are affected by inflammatory response during the course of leprosy, changes in the production of NGF and its receptor (NGF R) may be directly associated with disability and sensory loss. Skin biopsies were collected and submitted to immunohistochemistry using specific antibodies to IL-17, NGF and NGF R. Quantitative analysis of NGF, NGFR and IL-17 immunostaining showed a significant difference between the clinical forms, with higher expression of NGF and NGFR in lepromatous leprosy and IL-17 in tuberculoid leprosy. The present study showed that IL-17, in addition to stimulating an inflammatory response, negatively regulates the action of NGF and NGF R in the polar forms of the disease. PMID:26616164

  16. Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats.

    PubMed

    Dos Reis, Renata C; Kopruszinski, Caroline M; Nones, Carina F M; Chichorro, Juliana G

    2016-09-01

    There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain. PMID:27392124

  17. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.

    PubMed

    Chuang, H H; Prescott, E D; Kong, H; Shields, S; Jordt, S E; Basbaum, A I; Chao, M V; Julius, D

    2001-06-21

    Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex. These studies delineate a biochemical mechanism through which bradykinin and NGF produce hypersensitivity and might explain how the activation of PLC signalling systems regulates other members of the TRP channel family. PMID:11418861

  18. Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation.

    PubMed

    Perini, Irene; Tavakoli, Mitra; Marshall, Andrew; Minde, Jan; Morrison, India

    2016-08-01

    The rare nerve growth factor-β (NGFB) mutation R221W causes a selective loss of thinly myelinated fibers and especially unmyelinated C-fibers. Carriers of this mutation show altered pain sensation. A subset presents with arthropathic symptoms, with the homozygous most severely affected. The aim of the present study was to investigate the relationship between peripheral afferent loss and pain evaluation by performing a quantification of small-fiber density in the cornea of the carriers, relating density to pain evaluation measures. In vivo corneal confocal microscopy (CCM) was used to quantify C-fiber loss in the cornea of 19 R221W mutation carriers (3 homozygous) and 19 age-matched healthy control subjects. Pain evaluation data via the Situational Pain Questionnaire (SPQ) and the severity of neuropathy based on the Neuropathy Disability Score (NDS) were assessed. Homozygotes, heterozygotes, and control groups differed significantly in corneal C-nerve fiber density, with the homozygotes showing a significant afferent reduction. Importantly, peripheral C-fiber loss correlated negatively with pain evaluation, as revealed by SPQ scores. This study is the first to investigate the contribution of small-fiber density to the perceptual evaluation of pain. It demonstrates that the lower the peripheral small-fiber density, the lower the degree of reported pain intensity, indicating a functional relationship between small-fiber density and higher level pain experience. PMID:27146986

  19. Combinatorial Therapy with Tamoxifen And Trifluoperazine Effectively Inhibits Malignant Peripheral Nerve Sheath Tumor Growth by Targeting Complementary Signaling Cascades

    PubMed Central

    Brosius, Stephanie N.; Turk, Amy N.; Byer, Stephanie J.; Longo, Jody Fromm; Kappes, John C.; Roth, Kevin A.; Carroll, Steven L.

    2014-01-01

    Chemotherapeutic agents effective against malignant peripheral nerve sheath tumors (MPNSTs) are urgently needed. We recently found that tamoxifen potently impedes xenograft growth. In vitro, tamoxifen inhibits MPNST proliferation and survival in an estrogen receptor-independent manner; these effects are phenocopied by the calmodulin inhibitor trifluoperazine. The present study was performed to establish the mechanism of action of tamoxifen in vivo and optimize its therapeutic effectiveness. To determine if tamoxifen has estrogen receptor-dependent effects in vivo, we grafted MPNST cells in castrated and ovariectomized mice; xenograft growth was unaffected by reductions in sex hormones. To establish whether tamoxifen and trifluoperazine additively or synergistically impede MPNST growth, mice xenografted with NF1-associated or sporadic MPNST cells were treated with tamoxifen, trifluoperazine, or both drugs for 30 days. Both monotherapies inhibited graft growth by 50%, whereas combinatorial treatment maximally reduced graft mass by 90% and enhanced decreases in proliferation and survival. Kinomic analyses showed that tamoxifen and trifluoperazine have both shared and distinct targets in MPNSTs. Additionally, trifluoperazine prevented tamoxifen-induced increases in serum/glucocorticoid regulated kinase 1, a protein linked to tamoxifen resistance. These findings suggest that combinatorial therapy with tamoxifen and trifluoperazine is effective against MPNSTs because these agents target complementary pathways that are essential for MPNST pathogenesis. PMID:25289889

  20. Effect of transgenic human insulin-like growth factor-1 on spinal motor neurons following peripheral nerve injury

    PubMed Central

    GU, JIAXIANG; LIU, HONGJUN; ZHANG, NAICHEN; TIAN, HENG; PAN, JUNBO; ZHANG, WENZHONG; WANG, JINGCHENG

    2015-01-01

    The aim of the present study was to observe the protective effect of exogenous human insulin-like growth factor-1 (hIGF-1) on spinal motor neurons, following its local transfection into an area of peripheral nerve injury. A total of 90 male Wistar rats that had been established as sciatic nerve crush injury models were randomly divided into three groups: hIGF-1 treatment, sham-transfected control and blank control groups. The different phases of hIGF-1 expression were observed in the spinal cord via postoperative immunostaining and the apoptosis of motor neurons was observed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Pathological changes of the motor neurons and Nissl bodies within cell bodies were observed via Marsland and Luxol fast blue double staining, while changes in the neuropil of the spinal cord anterior horn were investigated via ultrastructural observation. It was found that hIGF-1, locally transfected into an area of peripheral nerve injury, was expressed in the spinal anterior horn following axoplasmic transport; the peak hIGF-1 expression occurred approximately a week following transfection. The number of apoptotic spinal cord motor neurons observed in the hIGF-1 treatment group was fewer than that in the sham-transfected and blank control groups at days 7, 14 and 21 following transfection (P<0.01). Furthermore, the quantity of motor neuron cells in the anterior horn of the spinal cord in the hIGF-1 treatment group was higher compared with those in the sham-transfected and blank control groups at days 2, 7, 14 and 28 following transfection (P<0.01). The degenerative changes of Nissl bodies within the cytoplasm of the hIGF-1 treatment group were less severe compared with those of the sham-transfected and blank control groups. At day 56 following transfection, the spinal anterior horn neuropil ultrastructure in the hIGF-1 treatment group was generally normal, while the sham-transfected and blank control

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

    SciTech Connect

    Matsushima, H.; Bogenmann, E. )

    1990-09-01

    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.

  2. Platelet-derived nerve growth factor supports the survival of cholinergic neurons in organotypic rat brain slices.

    PubMed

    Kniewallner, Kathrin M; Grimm, Natalia; Humpel, Christian

    2014-06-27

    Platelets play a role in repair of vessels and contain different growth factors, including nerve growth factor (NGF). Since NGF is the most potent growth factor to support survival of cholinergic neurons, we aimed to study the effects of platelet-derived NGF on cholinergic neurons in organotypic brain slices. Brain slices of the nucleus basalis of Meynert (nBM) were cultured with or without NGF (10ng/ml) or platelet extracts (100μg/ml) or fresh platelets (10(8) platelets/ml). In order to enhance NGF in platelets recombinant NGF (100ng) was loaded into platelets using ultrasound (3h). Our data show that recombinant NGF markedly supports survival of cholinergic neurons. The addition of fresh platelets showed a tendency for enhancing cholinergic neuron numbers, while platelet extracts had no effects. Ultrasound was highly effective to load recombinant NGF into platelets. The addition of NGF-loaded platelets markedly enhanced cholinergic neuron numbers. In conclusion, our data provide evidence that NGF-derived platelets may counteract cell death of cholinergic neurons. PMID:24861506

  3. INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

    EPA Science Inventory

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

  4. DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

    EPA Science Inventory


    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

  5. Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain

    SciTech Connect

    Altar, C.A.; Burton, L.E.; Bennett, G.L.; Dugich-Djordjevic, M. )

    1991-01-01

    Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF.

  6. Pinched Nerve

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Pinched Nerve Information Page Table of Contents (click to jump ... being done? Clinical Trials Organizations What is Pinched Nerve? The term "pinched nerve" is a colloquial term ...

  7. Nerve biopsy

    MedlinePlus

    Nerve biopsy may be done to help diagnose: Axon degeneration (destruction of the axon portion of the nerve cell) Damage to the ... Demyelination Inflammation of the nerve Leprosy Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis

  8. Effect of acute and chronic administration of L-tyrosine on nerve growth factor levels in rat brain.

    PubMed

    Ferreira, Gabriela K; Jeremias, Isabela C; Scaini, Giselli; Carvalho-Silva, Milena; Gomes, Lara M; Furlanetto, Camila B; Morais, Meline O; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2013-08-01

    Most inborn errors of tyrosine catabolism produce hypertyrosinemia. Neurological manifestations are variable and some patients are developmentally normal, while others show different degrees of developmental retardation. Considering that current data do not eliminate the possibility that elevated levels of tyrosine and/or its derivatives may have noxious effects on central nervous system development in some patients, the present study evaluated nerve growth factor (NGF) levels in hippocampus, striatum and posterior cortex of young rats. In our acute protocol, Wistar rats (10 and 30 days old) were killed 1 h after a single intraperitoneal administration of L-tyrosine (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); the rats were killed 12 h after the last injection. NGF levels were then evaluated. Our findings showed that acute administration of L-tyrosine decreased NGF levels in striatum of 10-day-old rats. In the 30-day-old rats, NGF levels were decreased in hippocampus and posterior cortex. On the other hand, chronic administration of L-tyrosine increased NGF levels in posterior cortex. Decreased NGF may impair growth, differentiation, survival and maintenance of neurons. PMID:23690230

  9. Selective translocation of protein kinase C-delta in PC12 cells during nerve growth factor-induced neuritogenesis.

    PubMed Central

    O'Driscoll, K R; Teng, K K; Fabbro, D; Greene, L A; Weinstein, I B

    1995-01-01

    The specific intracellular signals initiated by nerve growth factor (NGF) that lead to neurite formation in PC12 rat pheochromocytoma cells are as of yet unclear. Protein kinase C-delta (PKC delta) is translocated from the soluble to the particulate subcellular fraction during NGF-induced-neuritogenesis; however, this does not occur after treatment with the epidermal growth factor, which is mitogenic but does not induce neurite formation. PC12 cells also contain both Ca(2+)-sensitive and Ca(2+)-independent PKC enzymatic activities, and express mRNA and immunoreactive proteins corresponding to the PKC isoforms alpha, beta, delta, epsilon, and zeta. There are transient decreases in the levels of immunoreactive PKCs alpha, beta, and epsilon after 1-3 days of NGF treatment, and after 7 days there is a 2.5-fold increase in the level of PKC alpha, and a 1.8-fold increase in total cellular PKC activity. NGF-induced PC12 cell neuritogenesis is enhanced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) in a TPA dose- and time-dependent manner, and this differentiation coincides with abrogation of the down-regulation of PKC delta and other PKC isoforms, when the cells are treated with TPA. Thus a selective activation of PKC delta may play a role in neuritogenic signals in PC12 cells. Images PMID:7626808

  10. Temporal profile of nerve growth factor expression in the partial central nervous system of the Yangtze alligator Alligator sinensis (Reptilia,Crocodylia) during early postnatal growth.

    PubMed

    Zheng, Lanrong; Chen, Fangfang; Wang, Renping; Zhou, Yongkang; Wu, Xiaobing

    2013-05-01

    Expression of nerve growth factor (NGF) in structures of the partial central nervous system of the Yangtze alligator, Alligator sinensis (Reptilia, Crocodylia) was examined during early postnatal growth using immunohistochemistry and Western blot assays. In animals 0-2 years of age NGF-positive cells in the cerebral cortex increased gradually in number and size, and were predominantly distributed in the molecular layer. NGF-positive cells in the midbrain showed similar increases but with predominant distribution in the ependymal layer. NGF-positive cells increased in the cerebellum between 0 and 1 years of age, with increased NGF expression being seen during the first 2 years of life mostly in the ependymal layer. NGF-positive cells were mainly found in the gray matter of the spinal cord with decreasing cell numbers, NGF expression levels being seen from 0 to 2 years and small processes without synaptic connection from 1 to 2 years. These results suggest that NGF is involved in the early postnatal growth of several structures of Yangtze alligator partial central nervous system, suggesting a possible role of NGF in the Yangtze alligator partial central nervous system. PMID:23504856

  11. Nerve growth factor binds to normal human keratinocytes through high and low affinity receptors and stimulates their growth by a novel autocrine loop.

    PubMed

    Di Marco, E; Mathor, M; Bondanza, S; Cutuli, N; Marchisio, P C; Cancedda, R; De Luca, M

    1993-10-25

    Normal human keratinocytes synthesize and secrete biologically active nerve growth factor (NGF) in a growth regulated fashion (Di Marco, E., Marchisio, P. C., Bondanza, S., Franzi, A. T., Cancedda, R., and De Luca, M. (1991) J. Biol. Chem. 266, 21718-21722). Here we show that the same human keratinocytes bind NGF via low and high affinity receptors. In parallel with the course of NGF synthesis, the expression of low affinity NGF receptor (p75NGFr) decreases when a confluent, differentiated, and fully stratified epithelium is obtained. In skin sections, p75NGFr is present in basal keratinocytes and absent from suprabasal, terminally differentiated cells. The trkA protooncogene product (p140trkA), a component of the NGF receptor, is not expressed by keratinocytes. Instead, keratinocytes express a new member of the trk family (that we termed trkE), which generates 3.9-kilobase transcripts. Keratinocyte-derived NGF plays a key role in the autocrine epidermal cell proliferation. This has been proven by (i) direct effect of NGF on [3H]thymidine incorporation, (ii) inhibition of autocrine keratinocyte growth by monoclonal antibodies (alpha D11) inhibiting human NGF biological activity, and (iii) inhibition of autocrine keratinocyte proliferation by a trk-specific inhibitor, the natural alkaloid K252a. These data provide evidence that NGF, in addition to its effect as a survival and differentiation factor, is a potent regulator of cell proliferation, at least in human epithelial cells. PMID:7693679

  12. The Achyranthes bidentata polypeptide k fraction enhances neuronal growth in vitro and promotes peripheral nerve regeneration after crush injury in vivo

    PubMed Central

    Cheng, Qiong; Jiang, Chunyi; Wang, Caiping; Yu, Shu; Zhang, Qi; Gu, Xiaosong; Ding, Fei

    2014-01-01

    We have previously shown that Achyranthes bidentata polypeptides (ABPP), isolated from Achyranthes bidentata Blume (a medicinal herb), exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP. PMID:25657735

  13. Bridging nigrostriatal pathway with fibroblast growth factor-primed peripheral nerves and fetal ventral mesencephalon transplant recuperates from deficits in parkinsonian rats.

    PubMed

    Chiang, Yung-Hsiao; Lin, Shinn-Zong; Zhou, Feng C

    2006-01-01

    Previous studies have indicated that the nigrostriatal dopaminergic (DA) pathway can be reconstructed in hemiparkinsonian rats with a bridge transplantation technique involving fetal ventral mesencephalic transplants and glial cell line-derived neurotrophic factor. In this study, we examined if the nigrostriatal pathway can be restored by combining peripheral nervous tissue with the fetal ventral mesencephalon transplants. Adult rats were injected with 6-hydroxydopamine into left median forebrain bundle. Those with marked rotational behavior, which has been previously shown to indicate complete DA dennervtion, were used for transplant treatments. One month after the lesion, fetal ventral mesencephalic cells were transplanted into the nigral region followed by nigral-striatal grafting of peripheral nerves as a bridge. The bridging nerves (sciatic or intercostals) were pretreated with basic fibrous growth factor (nerve+bFGF+) or Hank's saline (nerve+bFGF-). We found that (a) animals receiving transplants of VM and bFGF+ nerve had a reduction in rotational behavior; (b) animals receiving bFGF-- nerve bridge only had a partial improvement in rotation. Reinnervation of tyrosine hydroxylase (TH)-immunoreactive (ir) fibers into the striatum was found in both of the above groups with more innervation in the former than in the latter. No TH-ir fibers in lesioned striatum or reduction in rotational behavior were found in animals receiving VM only, or VM plus bFGF. Taken together, our data indicate that peripheral nerve, with the aid of bFGF, greatly facilitates the reconstitution of the TH pathway from nigra to striatum and improves motor function in hemiparkinsonian rats. PMID:17121158

  14. Perinatal Epidermal Growth Factor Receptor Blockade Prevents Peripheral Nerve Disruption in a Mouse Model Reminiscent of Benign World Health Organization Grade I Neurofibroma

    PubMed Central

    Wu, Jianqiang; Crimmins, Jason T.; Monk, Kelly R.; Williams, Jon P.; Fitzgerald, Maureen E.; Tedesco, Susan; Ratner, Nancy

    2006-01-01

    Benign peripheral nerve tumors called neurofibromas are a major source of morbidity for patients with neurofibromatosis type 1. Some neurofibroma Schwann cells aberrantly express the epidermal growth factor receptor (EGFR). In a mouse model in which the CNPase promoter drives expression of human EGFR in Schwann cells, nerves develop hypertrophy, mast cell accumulation, collagen deposition, disruption of axon-glial interactions, characteristics of neurofibroma and are hypoalgesic. Administration of the EGFR antagonist cetuximab (IMC-C225) for 2 weeks beginning at birth in CNPase-hEGFR mice normalized all pathologies at 3 months of age as evaluated by hotplate testing or histology and by electron microscopy. Mast cell chemoattractants brain-derived neurotrophic factor, monocyte chemoattractant protein-1, and transforming growth factor-β1, which may account for mast cell accumulation and fibrosis, were reduced by cetuximab. Later treatment was much less effective. A birth to 2-week pulse of cetuximab blocked hEGFR phosphorylation and Schwann cell proliferation in perinatal mutant nerve, so CNPase-hEGFR Schwann cell numbers correlate with the cetuximab effect. A >250-fold enlarged population of EGFR+/p75+ cells was detected in newborn Nf1+/− mouse nerves. These results suggest the existence of an EGFR+ cell enriched in the perinatal period capable of driving complex changes characteristic of neurofibroma formation. PMID:16651634

  15. A modular, plasmin-sensitive, clickable poly(ethylene glycol)-heparin-laminin microsphere system for establishing growth factor gradients in nerve guidance conduits.

    PubMed

    Roam, Jacob L; Yan, Ying; Nguyen, Peter K; Kinstlinger, Ian S; Leuchter, Michael K; Hunter, Daniel A; Wood, Matthew D; Elbert, Donald L

    2015-12-01

    Peripheral nerve regeneration is a complex problem that, despite many advancements and innovations, still has sub-optimal outcomes. Compared to biologically derived acellular nerve grafts and autografts, completely synthetic nerve guidance conduits (NGC), which allow for precise engineering of their properties, are promising but still far from optimal. We have developed an almost entirely synthetic NGC that allows control of soluble growth factor delivery kinetics, cell-initiated degradability and cell attachment. We have focused on the spatial patterning of glial-cell derived human neurotrophic factor (GDNF), which promotes motor axon extension. The base scaffolds consisted of heparin-containing poly(ethylene glycol) (PEG) microspheres. The modular microsphere format greatly simplifies the formation of concentration gradients of reversibly bound GDNF. To facilitate axon extension, we engineered the microspheres with tunable plasmin degradability. 'Click' cross-linking chemistries were also added to allow scaffold formation without risk of covalently coupling the growth factor to the scaffold. Cell adhesion was promoted by covalently bound laminin. GDNF that was released from these microspheres was confirmed to retain its activity. Graded scaffolds were formed inside silicone conduits using 3D-printed holders. The fully formed NGC's contained plasmin-degradable PEG/heparin scaffolds that developed linear gradients in reversibly bound GDNF. The NGC's were implanted into rats with severed sciatic nerves to confirm in vivo degradability and lack of a major foreign body response. The NGC's also promoted robust axonal regeneration into the conduit. PMID:26352518

  16. Heparin modulation of the neurotropic effects of acidic and basic fibroblast growth factors and nerve growth factor on PC12 cells

    SciTech Connect

    Neufeld, G.; Gospodarowicz, D.; Dodge, L.; Fujii, D.K.

    1987-04-01

    Nerve growth factor (NGF) and acidic or basic fibroblast growth factor (aFGF and bFGF, respectively) induce neurite outgrowth from the rat pheochromocytoma cell line, PC12. The neurites induced by these three factors are stable for up to a month in cell culture in the continued presence of any of the above growth factors. bFGF (ED50 = 30 pg/ml) is 800 fold more potent in stimulating neurite outgrowth than aFGF (ED50 = 25 ng/ml) and 260 fold more potent than NGF (ED50 = 8 ng/ml). While the neurotropic activities of aFGF and NGF are potentiated by heparin, that of bFGF is both partially inhibited or stimulated, depending upon the concentration of bFGF. Radioreceptor binding experiments show that aFGF and bFGF bind to a common binding site on the PC12 cell surface. Affinity labeling studies demonstrate a single receptor with an apparent molecular weight of 145,000 daltons, which corresponds to the high molecular weight receptor identified in BHK-21 cells. NGF does not appear to compete with aFGF or bFGF for binding to the receptor. Heparin blocked the binding of bFGF to the receptor but had only a small inhibitory effect on the binding of aFGF to the receptor. Thus, it appears that heparin inhibition of the neurotropic effects of bFGF occurs, at least in part, by impairing the interaction of bFGF with the receptor, while having little effect on that of aFGF. The stimulatory effects of heparin on the neurotropic activity of aFGF, bFGF, and NGF may occur through a site not associated with the respective cellular receptor for the growth factors.

  17. TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization.

    PubMed

    Goswami, C; Schmidt, H; Hucho, F

    2007-02-01

    While the importance of Ca(2+) channel activity in axonal path finding is established, the underlying mechanisms are not clear. Here, we show that transient receptor potential vanilloid receptor 1 (TRPV1), a member of the TRP superfamily of nonspecific ion channels, is physically and functionally present at dynamic neuronal extensions, including growth cones. These nonselective cation channels sense exogenous ligands, such as resenifera toxin, and endogenous ligands, such as N-arachidonoyl-dopamine (NADA), and affect the integrity of microtubule cytoskeleton. Using TRPV1-transiently transfected F11 cells and embryonic dorsal root ganglia explants, we show that activation of TRPV1 results in growth cone retraction, and collapse and formation of varicosities along neurites. These changes were due to TRPV1-activation-mediated disassembly of microtubules and are partly Ca(2+)-independent. Prolonged activation with very low doses (1 nM) of NADA results in shortening of neurites in the majority of isolectin B4-positive dorsal root ganglia neurones. We postulate that TRPV1 activation plays an inhibitory role in sensory neuronal extension and motility by regulating the disassembly of microtubules. This might have a role in the chronification of pain. PMID:17288556

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

    PubMed Central

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

    2013-01-01

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

  19. Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor.

    PubMed Central

    Rodríguez-Tébar, A; Dechant, G; Götz, R; Barde, Y A

    1992-01-01

    Neurotrophin-3 (NT-3) has low-affinity (Kd = 8 x 10(-10) M), as well as high-affinity receptors (Kd = 1.8 x 10(-11) M) on embryonic chick sensory neurons, the latter in surprisingly high numbers. Like the structurally related proteins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), NT-3 also binds to the low-affinity NGF receptor, a molecule that we suggest to designate low-affinity neurotrophin receptor (LANR). NT-3 dissociates from the LANR much more rapidly than BDNF, and more slowly than NGF. The binding of labelled NT-3 to the LANR can be reduced by half using a concentration of BDNF corresponding to the Kd of BDNF to the LANR. In contrast, the binding of NT-3 to its high-affinity neuronal receptors can only be prevented by BDNF or NGF when used at concentrations several thousand-fold higher than those corresponding to their Kd to their high-affinity neuronal receptors. Thus, specific high-affinity NT-3 receptors exist on sensory neurons that can readily discriminate between three structurally related ligands. These findings, including the remarkable property of the LANR to bind three related ligands with similar affinity, but different rate constants, are discussed. PMID:1547788

  20. Nerve Growth Factor Regulation by TNF-α and IL-1β in Synovial Macrophages and Fibroblasts in Osteoarthritic Mice

    PubMed Central

    Takano, Shotaro; Inoue, Gen; Aikawa, Jun; Iwase, Dai; Minatani, Atsushi; Iwabuchi, Kazuya; Takaso, Masashi

    2016-01-01

    To investigate the role of macrophages as a regulator and producer of nerve growth factor (NGF) in the synovial tissue (ST) of osteoarthritis (OA) joints, the gene expression profiles of several inflammatory cytokines in the ST, including synovial macrophages and fibroblasts, of OA mice (STR/Ort) were characterized. Specifically, real-time polymerase chain reaction analysis was used to evaluate the expression of tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and NGF in CD11b+ and CD11b– cells isolated from the ST of a murine OA model. The effects of TNF-α, IL-1β, and IL-6 on the expression of NGF in cultured synovial cells were also examined. The expression of TNF-α, IL-1β, IL-6, and NGF in the ST of STR/Ort was higher than that in C57/BL6J mice. Compared to the CD11b– cell fraction, higher expression levels of TNF-α, IL-1β, and IL-6 were detected in the CD11b+ cell fraction, whereas no differences in the expression of NGF were detected between the two cell fractions. Notably, TNF-α upregulated NGF expression in synovial fibroblasts and macrophages and IL-1β upregulated NGF expression in synovial fibroblasts. IL-1β and TNF-α may regulate NGF signaling in OA joints and be suitable therapeutic targets for treating OA pain.

  1. Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of Nerve Growth Factor.

    PubMed

    Jarvis, Thale C; Davies, Douglas R; Hisaminato, Akihiko; Resnicow, Daniel I; Gupta, Shashi; Waugh, Sheela M; Nagabukuro, Akira; Wadatsu, Takashi; Hishigaki, Haretsugu; Gawande, Bharat; Zhang, Chi; Wolk, Steven K; Mayfield, Wesley S; Nakaishi, Yuichiro; Burgin, Alex B; Stewart, Lance J; Edwards, Thomas E; Gelinas, Amy D; Schneider, Daniel J; Janjic, Nebojsa

    2015-07-01

    Discerning the structural building blocks of macromolecules is essential for understanding their folding and function. For a new generation of modified nucleic acid ligands (called slow off-rate modified aptamers or SOMAmers), we previously observed essential functions of hydrophobic aromatic side chains in the context of well-known nucleic acid motifs. Here we report a 2.45-Å resolution crystal structure of a SOMAmer complexed with nerve growth factor that lacks any known nucleic acid motifs, instead adopting a configuration akin to a triangular prism. The SOMAmer utilizes extensive hydrophobic stacking interactions, non-canonical base pairing and irregular purine glycosidic bond angles to adopt a completely non-helical, compact S-shaped structure. Aromatic side chains contribute to folding by creating an unprecedented intercalating zipper-like motif and a prominent hydrophobic core. The structure provides compelling rationale for potent inhibitory activity of the SOMAmer and adds entirely novel motifs to the repertoire of structural elements uniquely available to SOMAmers. PMID:26027732

  2. Brain-derived neurotrophic factor and nerve growth factor potentiate excitatory synaptic transmission in the rat visual cortex.

    PubMed Central

    Carmignoto, G; Pizzorusso, T; Tia, S; Vicini, S

    1997-01-01

    1. The effect of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) on excitatory synaptic transmission in the developing visual cortex was studied by whole-cell patch-clamp recordings from rat brain slices. 2. Both neurotrophins induced a rapid increase in the amplitude of impulse-evoked excitatory postsynaptic currents (EPSCs). BDNF also increased the frequency of spontaneous EPSCs. 3. Analysis of the currents revealed that alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components contributing to the EPSC peak amplitude were equally potentiated by the neurotrophins. 4. When synaptic transmission was studied by minimal stimulation of intracortical afferents, neurotrophins induced a decrease in the occurrence of release failures. 5. A number of neurones were insensitive to the effects of the neurotrophins, possibly related to the considerable heterogeneity of neuronal types and to the uneven distribution of neurotrophin receptors in the visual cortex. 6. The probability of neurotransmitter release represents a rapidly modifiable synaptic feature by which neurotrophins can potentiate the efficacy of excitatory synaptic transmission in the visual cortex. PMID:9023775

  3. Antibodies directed to Neisseria gonorrhoeae impair nerve growth factor-dependent neurite outgrowth in Rat PC12 cells.

    PubMed

    Reuss, B

    2014-03-01

    In children born from mothers with prenatal infections with the Gram-negative bacterium Neisseria gonorrhoeae, schizophrenia risk is increased in later life. Since cortical neuropil formation is frequently impaired during this disease, actions of a rabbit polyclonal antiserum directed to N. gonorrhoeae on neurite outgrowth in nerve growth factor-stimulated PC12 cells were investigated here. It turned out that 10 μg/ml of the antiserum leads indeed to a significant reduction in neurite outgrowth, whereas an antiserum directed to Neisseria meningitidis had no such effect. Furthermore, reduction in neurite outgrowth could be reversed by the neuroleptic drugs haloperidol, clozapine, risperidone, and olanzapine. On the molecular level, the observed effects seem to include the known neuritogenic transcription factors FoxO3a and Stat3, since reduced neurite outgrowth caused by the antiserum was accompanied by a reduced phosphorylation of both factors. In contrast, restitution of neurite outgrowth by neuroleptic drugs revealed no correlation to the phosphorylation state of these factors. The present report gives a first hint that bacterial infections could indeed lead to impaired neuropil formation in vitro; however, the in vivo relevance of this finding for schizophrenia pathogenesis remains to be clarified in the future. PMID:24203572

  4. Up-Regulation of Nerve Growth Factor in Cholestatic Livers and Its Hepatoprotective Role against Oxidative Stress

    PubMed Central

    Tsai, Ming-Shian; Lin, Yu-Chun; Sun, Cheuk-Kwan; Huang, Shih-Che; Lee, Po-Huang; Kao, Ying-Hsien

    2014-01-01

    The role of nerve growth factor (NGF) in liver injury induced by bile duct ligation (BDL) remains elusive. This study aimed to investigate the relationship between inflammation and hepatic NGF expression, to explore the possible upstream molecules up-regulating NGF, and to determine whether NGF could protect hepatocytes from oxidative liver injury. Biochemical and molecular detection showed that NGF was up-regulated in cholestatic livers and plasma, and well correlated with systemic and hepatic inflammation. Conversely, systemic immunosuppression reduced serum NGF levels and resulted in higher mortality in BDL-treated mice. Immunohistochemistry showed that the up-regulated NGF was mainly localized in parenchymal hepatocytes. In vitro mechanistic study further demonstrated that TGF-β1 up-regulated NGF expression in clone-9 and primary rat hepatocytes. Exogenous NGF supplementation and endogenous NGF overexpression effectively protected hepatocytes against TGF-β1- and oxidative stress-induced cell death in vitro, along with reduced formation of oxidative adducted proteins modified by 4-HNE and 8-OHdG. TUNEL staining confirmed the involvement of anti-apoptosis in the NGF-exhibited hepatoprotection. Moreover, NGF potently induced Akt phosphorylation and increased Bcl-2 to Bax ratios, whereas these molecular alterations by NGF were only seen in the H2O2-, but not TGF-β1-treated hepatocytes. In conclusion, NGF exhibits anti-oxidative and hepatoprotective effects and is suggested to be therapeutically applicable in treating cholestatic liver diseases. PMID:25397406

  5. Up-regulation of nerve growth factor in cholestatic livers and its hepatoprotective role against oxidative stress.

    PubMed

    Tsai, Ming-Shian; Lin, Yu-Chun; Sun, Cheuk-Kwan; Huang, Shih-Che; Lee, Po-Huang; Kao, Ying-Hsien

    2014-01-01

    The role of nerve growth factor (NGF) in liver injury induced by bile duct ligation (BDL) remains elusive. This study aimed to investigate the relationship between inflammation and hepatic NGF expression, to explore the possible upstream molecules up-regulating NGF, and to determine whether NGF could protect hepatocytes from oxidative liver injury. Biochemical and molecular detection showed that NGF was up-regulated in cholestatic livers and plasma, and well correlated with systemic and hepatic inflammation. Conversely, systemic immunosuppression reduced serum NGF levels and resulted in higher mortality in BDL-treated mice. Immunohistochemistry showed that the up-regulated NGF was mainly localized in parenchymal hepatocytes. In vitro mechanistic study further demonstrated that TGF-β1 up-regulated NGF expression in clone-9 and primary rat hepatocytes. Exogenous NGF supplementation and endogenous NGF overexpression effectively protected hepatocytes against TGF-β1- and oxidative stress-induced cell death in vitro, along with reduced formation of oxidative adducted proteins modified by 4-HNE and 8-OHdG. TUNEL staining confirmed the involvement of anti-apoptosis in the NGF-exhibited hepatoprotection. Moreover, NGF potently induced Akt phosphorylation and increased Bcl-2 to Bax ratios, whereas these molecular alterations by NGF were only seen in the H2O2-, but not TGF-β1-treated hepatocytes. In conclusion, NGF exhibits anti-oxidative and hepatoprotective effects and is suggested to be therapeutically applicable in treating cholestatic liver diseases. PMID:25397406

  6. Characteristic element of matrix attachment region mediates vector attachment and enhances nerve growth factor expression in Chinese hamster ovary cells.

    PubMed

    Wang, X Y; Zhang, J H; Sun, Q L; Yao, Z Y; Deng, B G; Guo, W Y; Wang, L; Dong, W H; Wang, F; Zhao, C P; Wang, T Y

    2015-01-01

    Preliminary studies have suggested that a characteristic element of the matrix attachment region (MAR) in human interferon-β mediates the adhesion of vectors to Chinese hamster ovary (CHO) cells. In this study, we investigated if vector adhesion increased nerve growth factor (NGF) expression in CHO cells. The MAR characteristic element sequence of human interferon-β was inserted into the multiple-cloning site of the pEGFP-C1 vector. The target NGF gene was inserted upstream of the MAR characteristic element sequence to construct the MAR/NGF expression vector. The recombinant plasmid was transfected into CHO cells and stable monoclonal cells were selected using G418. NGF mRNA and protein expression was detected by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Plasmid reduction experiments were used to determine the state of transfected plasmid in mammalian cells. The insertion of MAR into the vector increased NGF expression levels in CHO cells (1.93- fold) compared to the control. The recombinant plasmid expressing the MAR sequence was digested into a linear space vector. The inserted MAR and NGF sequences were consistent with those inserted into the plasmid before recombination. Therefore, we concluded that the MAR characteristic element mediates vector adhesion to CHO cells and enhances the stability and efficiency of the target gene expression. PMID:26345852

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

    PubMed

    Fjord-Larsen, L; Kusk, P; Emerich, D F; Thanos, C; Torp, M; Bintz, B; Tornøe, J; Johnsen, A H; Wahlberg, L U

    2012-10-01

    Nerve growth factor (NGF) is a potential therapeutic agent for Alzheimer's disease (AD) as it has positive effects on the basal forebrain cholinergic neurons whose degeneration correlates with the cognitive decline in AD. We have previously described an encapsulated cell biodelivery device, NsG0202, capable of local delivery of NGF by a genetically modified human cell line, NGC-0295. The NsG0202 devices have shown promising safety and therapeutic results in a small phase 1b clinical study. However, results also show that the NGF dose could advantageously be increased. We have used the sleeping beauty transposon expression technology to establish a new clinical grade cell line, NGC0211, with at least 10 times higher NGF production than that of NGC-0295. To test whether encapsulation of this cell line provides a relevant dose escalation step in delivering NGF for treatment of the cognitive decline in AD patients, we have validated the bioactivity of devices with NGC0211 and NGC-0295 cells in normal rat striatum as well as in the quinolinic acid striatal lesion model. These preclinical animal studies show that implantation of devices with NGC0211 cells lead to significantly higher NGF output, which in both cases correlate with highly improved potency. PMID:22113314

  8. Sargaquinoic acid supports the survival of neuronal PC12D cells in a nerve growth factor-independent manner.

    PubMed

    Tsang, Chi Kwan; Kamei, Yuto

    2004-03-19

    Sargaquinoic acid (designated previously as MC14) was isolated from a marine brown alga Sargassum macrocarpum, and has been found to possess a novel nerve growth factor (NGF)-dependent neurite outgrowth promoting activity in PC12D cells. In this study, we explored the neuroprotective effects of MC14 in terms of its survival supporting, antioxidant and neurite-regenerating activities under NGF deficient or deprived conditions. Intriguingly, MC14 did not only promote the NGF-induced survival support on neuronal PC12D cells, but also significantly abated neuronal PC12D cell death even in the absence of NGF. The pharmacological inhibition of phosphatidylinositol-3 kinase (PI3K) by wortmannin significantly suppressed the survival supporting activity of MC14, whereas the NGF receptor (tyrosine kinase A or TrkA) inhibitor K252a showed no detectable effect on MC14 activity. These results demonstrate that MC14 supports survival of neuronal PC12D cells in an NGF-independent manner, and that PI3K may be required for the neuroprotective activity of MC14. In addition, we have shown that MC14 markedly enhanced neurite-regeneration and protected PC12D cells from hydrogen peroxide (H(2)O(2))-induced oxidative stress. These pharmacological features suggest that MC14 may be a potentially important neuroprotective agent. PMID:15044030

  9. Side-stream tobacco smoke-induced airway hyperresponsiveness in early postnatal period is involved nerve growth factor.

    PubMed

    Wu, Z-X; Hunter, D D; Batchelor, T P; Dey, R D

    2016-03-01

    Epidemiological studies have shown that children are more susceptible to adverse respiratory effects of passive smoking than adults. The goal of this study is to elucidate the possible neural mechanism induced by exposure to passive smoking during early life. Postnatal day (PD) 2 and PD 21 mice were exposed to side-stream tobacco smoke (SS), a surrogate to secondhand smoke, or filtered air (FA) for 10 consecutive days. Pulmonary function, substance P (SP) airway innervation, neurotrophin gene expression in lung and nerve growth factor (NGF) release in bronchoalveolar lavage (BAL) fluid were measured at different times after the last SS or FA exposure. Exposure to SS significantly altered pulmonary function in PD2, accompanied with an enhanced SP innervation in airway. However, exposure to SS during the later developmental period (PD21) did not appear to affect pulmonary function and SP innervation of the airways. Interestingly, SS exposure in PD2 group significantly induced an increased gene expression on NGF, and decreased NGF receptor P75 in lung; parallel with high levels of NGF protein in BAL. Furthermore, pretreatment with NGF antibody significantly diminished SS-induced airway hyperresponsivenss and the increased SP airway innervation in the PD2 group. These findings suggest that enhanced NGF released in the lung contributes to SS-enhanced SP tracheal innervation and airway responsiveness in early life. PMID:26638730

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

    PubMed Central

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

    2010-01-01

    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. PMID:20664524

  11. Fiber-optic immuno-biosensor for rapid and accurate detection of nerve growth factor in human blood.

    PubMed

    Tang, Liang; Cha, Yong-Mei; Li, Hongmei; Chen, Peng-Sheng; Lin, Shien-Fong

    2006-01-01

    An accurate and rapid assay of cardiac nerve growth factor (NGF) levels in blood can provide physicians with critical information regarding myocardial injury and neural remodeling in cardiac tissues to identify patients at risk of impending heart attack, thereby enabling them to receive appropriate lifesaving treatment more quickly. Currently used assay methods, such as enzyme-linked immunosorbent assay (ELISA), are usually time-consuming (hours to days), expensive and technically complicated. In this paper, we described the development and clinical study of a rapid and sensitive method for detection and quantification of NGF in human blood plasma. This method utilizes a fiber-optic, immuno-biosensing system which performs a fluorophore-mediated sandwich immunoassay on the surface of an optical fiber. Physiological concentrations of NGF could be quantified in both buffer and human blood plasma samples within 5 minutes. The NGF concentrations determined by the fiberoptic sensor were comparable to those by the gold standard, ELISA. Preliminary study of NGF assay in cardiac patient plasma samples showed a great potential of the fiber-optic sensor as a rapid diagnostic and prognostic tool in clinical applications. PMID:17946002

  12. Vitamin A increases nerve growth factor and retinoic acid receptor beta and improves diabetic neuropathy in rats.

    PubMed

    Hernández-Pedro, Norma; Granados-Soto, Vinicio; Ordoñez, Graciela; Pineda, Benjamin; Rangel-López, Edgar; Salazar-Ramiro, Aleli; Arrieta, Oscar; Sotelo, Julio

    2014-09-01

    All-trans retinoic acid (ATRA) promotes the endogenous expression of both nerve growth factor (NGF) and retinoic acid receptor beta (RAR-β). We have previously shown that the administration of ATRA partly reverts the damage induced by diabetic neuropathy (DN). In this investigation, we evaluated the effects of vitamin A, a commercial, inexpensive compound of retinoic acid, on the therapy of DN. A total of 70 rats were randomized into 4 groups. Group A was the control, and groups B, C, and D received a total dose of 60 mg/kg streptozotocin intraperitoneally. When signs of DN developed, groups C and D were treated either with vitamin A (20,000 IU) or with ATRA 25 mg/kg for 60 days. Plasma glucose, contents of NGF, thermal and nociceptive tests, and RAR-β expression were evaluated. All diabetic rats developed neuropathy. The treatment with vitamin A and ATRA reverted similarly the sensorial disturbances, which was associated with increased contents of NGF and RAR-β expression. Our results indicate that the administration of vitamin A has the same therapeutic effect as ATRA on peripheral neuropathy and suggest its potential therapeutic use in patients with diabetes. PMID:24768685

  13. Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

    PubMed

    Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

    2016-07-01

    Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells. PMID:27128150

  14. Nerve growth factor-induced differentiation of PC12 cells is accompanied by elevated adenylyl cyclase activity.

    PubMed

    Yung, H S; Lai, K H; Chow, K B S; Ip, N Y; Tsim, K W K; Wong, Y H; Wu, Z; Wise, H

    2010-01-01

    Rat pheochromocytoma (PC12) cells characteristically undergo differentiation when cultured with nerve growth factor (NGF). Here we show that NGF dramatically increased the adenylyl cyclase-activating property of forskolin in PC12 cells. This effect of NGF was well maintained even when NGF was removed after 4 days, even though the morphological features of neuronal differentiation were rapidly lost on removal of NGF. The enhanced cAMP production in response to forskolin could be due to a synergistic interaction between forskolin and endogenously released agonists acting on G(s)-coupled receptors. However, responses to forskolin were not attenuated by antagonists of adenosine A2 receptors or pituitary adenylate cyclase-activating polypeptide (PACAP) receptors, suggesting that adenosine and PACAP were not involved. Adenylyl cyclases 3, 6 and 9 were the predominant isoforms expressed in PC12 cells, but we found no evidence for NGF-induced changes in expression levels of any of the 9 adenylyl cyclase isoforms, nor in the expression of Gα(s). These findings highlight that NGF has a subtle influence on adenylyl cyclase activity in PC12 cells which may influence more than the neurite extension process classically associated with neuronal differentiation. PMID:20389133

  15. Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?*

    PubMed Central

    Xu, Xiao-juan; Liu, Liang; Yao, Shu-kun

    2016-01-01

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D. PMID:26739521

  16. Sustained local delivery of bioactive nerve growth factor in the central nervous system via tunable diblock copolypeptide hydrogel depots.

    PubMed

    Song, Bingbing; Song, Jinsuk; Zhang, Shanshan; Anderson, Mark A; Ao, Yan; Yang, Chu-Ya; Deming, Timothy J; Sofroniew, Michael V

    2012-12-01

    Biomaterial vehicles that can provide sustained, site-specific molecular delivery in the central nervous system (CNS) have potential for therapeutic and investigative applications. Here, we present in vitro and in vivo proof of principle tests of diblock copolypeptide hydrogels (DCH) to serve as depots for sustained local release of protein effector molecules. We tested two DCH, K(180)L(20) and E(180)L(20), previously shown to self-assemble into biocompatible, biodegradable deposits that persist four to eight weeks after injection into mouse forebrain. In vitro tests demonstrated sustained release from dialysis cassettes of the representative protein, lysozyme, dissolved in K(180)L(20) or E(180)L(20) hydrogels. Release time in vitro varied in relation to DCH charge and mechanical properties, and ionic strength of the media. To evaluate bioactive protein delivery in vivo, we used nerve growth factor (NGF) and measured the size of mouse forebrain cholinergic neurons, which respond to NGF with cellular hypertrophy. For in vivo tests, the storage modulus of DCH depots was tuned to just below that of CNS tissue. In comparison with NGF injected in buffer, depots of NGF dissolved in either K(180)L(20) or E(180)L(20) provided significantly longer delivery of NGF bioactivity, maintaining hypertrophy of local forebrain cholinergic neurons for at least 4 weeks and inducing hypertrophy a further distance away (up to 5 mm) from injection sites. These findings show that depots of DCH injected into CNS can provide sustained delivery within the blood-brain barrier of a bioactive protein growth factor that exerts a predicted, quantifiable effect on local cells over a prolonged subacute time. PMID:22985994

  17. Effects of nerve growth factor and heart cell conditioned medium on neurite regeneration of aged sympathetic neurons in culture.

    PubMed

    Uchida, Y; Tomonaga, M

    1985-11-25

    The effects of nerve growth factor (NGF) and heart-cell-conditioned medium (HCM) on the neurite regeneration of aged sympathetic neurons were investigated in culture. Investigation of HCM was carried out by two different methods: one was the use of whole HCM on collagen substratum, which reflected component(s) effective in solution (HCM-S); the other was the use of polyornithine (PORN)-binding component(s) (P-HCM). Superior cervical ganglion neurons prepared from male mice from 6 to 30 months of age were cultured in MEM-10% FCS on collagen or gelatin-PORN substratum for 3 days. The number of neurons with neurites and the length of neurites were quantified as neurite production and elongation, respectively. Neuronal survival was not affected by addition of NGF, HCM-S or P-HCM. Neurite production of early adult neurons was enhanced by NGF, HCM-S or P-HCM. In contrast, neurite production of aged neurons was enhanced by only HCM-S, but not NGF or P-HCM. HCM-S did not promote neurite elongation in neurons at any age. Neurite elongation of early adult neurons was enhanced by NGF or P-HCM. Neurite elongation of aged neurons was enhanced by P-HCM. However, responsiveness of NGF for neurite elongation varied according to substrata. No age-related difference was found in neurite production and elongation in the absence of NGF, HCM-S or P-HCM. These results indicate that responsiveness of aged sympathetic neurons is various in different growth factors. PMID:3840716

  18. The Evaluation of Nerve Growth Factor Over Expression on Neural Lineage Specific Genes in Human Mesenchymal Stem Cells

    PubMed Central

    Mortazavi, Yousef; Sheikhsaran, Fatemeh; Khamisipour, Gholamreza Khamisipour; Soleimani, Masoud; Teimuri, Ali; Shokri, Somayeh

    2016-01-01

    Objective Treatment and repair of neurodegenerative diseases such as brain tumors, spinal cord injuries, and functional disorders, including Alzheimer’s disease, are challenging problems. A common treatment approach for such disorders involves the use of mesenchymal stem cells (MSCs) as an alternative cell source to replace injured cells. However, use of these cells in hosts may potentially cause adverse outcomes such as tumorigenesis and uncontrolled differentiation. In attempt to generate mesenchymal derived neural cells, we have infected MSCs with recombinant lentiviruses that expressed nerve growth factor (NGF) and assessed their neural lineage genes. Materials and Methods In this experimental study, we cloned the NGF gene sequence into a helper dependent lentiviral vector that contained the green fluorescent protein (GFP) gene. The recombinant vector was amplified in DH5 bacterial cells. Recombinant viruses were generated in the human embryonic kidney 293 (HEK-293) packaging cell line with the helper vectors and analyzed under fluorescent microscopy. Bone marrow mesenchymal cells were infected by recombinant viruses for three days followed by assessment of neural differentiation. We evaluated expression of NGF through measurement of the NGF protein in culture medium by ELISA; neural specific genes were quantified by real-time polymerase chain reaction (PCR). Results We observed neural morphological changes after three days. Quantitative PCR showed that expressions of NESTIN, glial derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP) and Microtubule-associated protein 2 (MAP2) genes increased following induction of NGF overexpression, whereas expressions of endogenous NGF and brain derived neural growth factor (BDNF) genes reduced. Conclusion Ectopic expression of NGF can induce neurogenesis in MSCs. Direct injection of MSCs may cause tumorigenesis and an undesirable outcome. Therefore an alternative choice to overcome this obstacle may

  19. Nerve Growth Factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia

    PubMed Central

    Diao, Yong-Peng; Cui, Feng-Kui; Yan, Sheng; Chen, Zuo-Guan; Lian, Li-Shan; Guo, Li-Long; Li, Yong-Jun

    2016-01-01

    Background: Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis. This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis. Methods: Twenty-four mice were randomly allocated to normal control group (n = 6), blank control group (n = 6), VEGF gene transfection group (n = 6), and NGF gene transfection group (n = 6). The model of left hindlimb ischemia model was established by ligating the femoral artery. VEGF165 plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively. Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction. The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining. NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay. Results: On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group. The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P < 0.05). The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P < 0.05). Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P < 0.05), but there was no significant difference of the

  20. The failed attribution of the Nobel Prize for Medicine or Physiology to Viktor Hamburger for the discovery of Nerve Growth Factor.

    PubMed

    Ribatti, Domenico

    2016-06-01

    The announcement in October 1986 that the Nobel Prize for Physiology or Medicine was to awarded to Rita Levi Montalcini and Stanley Cohen for the discovery of nerve growth factor (NGF) and epidermal growth factor, respectively, caused many to wonder why Viktor Hamburger in whose laboratory the initial work was done had not been included in the award. This article try to reconstruct the history of the discovery of NGF with the aim to re-establish a correct dynamic of the events. PMID:26930162

  1. Molecular cloning of the mouse grb2 gene: differential interaction of the Grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors.

    PubMed Central

    Suen, K L; Bustelo, X R; Pawson, T; Barbacid, M

    1993-01-01

    We report the isolation and molecular characterization of the mouse grb2 gene. The product of this gene, the Grb2 protein, is highly related to the Caenorhabditis elegans sem-5 gene product and the human GRB2 protein and displays the same SH3-SH2-SH3 structural motifs. In situ hybridization studies revealed that the mouse grb2 gene is widely expressed throughout embryonic development (E9.5 to P0). However, grb2 transcripts are not uniformly distributed, and in certain tissues (e.g., thymus) they appear to be regulated during development. Recent genetic and biochemical evidence has implicated the Grb2 protein in the signaling pathways that link cell surface tyrosine kinase receptors with Ras. We have investigated the association of the Grb2 protein with epidermal growth factor (EGF) and nerve growth factor (NGF) receptors in PC12 pheochromocytoma cells. EGF treatment of PC12 cells results in the rapid association of Grb2 with the activated EGF receptors, an interaction mediated by the Grb2 SH2 domain. However, Grb2 does not bind to NGF-activated Trk receptors. Mitogenic signaling of NGF in NIH 3T3 cells ectopically expressing Trk receptors also takes place without detectable association between Grb2 and Trk. These results suggest that whereas EGF and NGF can activate the Ras signaling pathway in PC12 cells, only the EGF receptor is likely to do so through a direct interaction with Grb2. Finally, binding studies with glutathione S-transferase fusion proteins indicate that Grb2 binds two distinct subsets of proteins which are individually recognized by its SH2 and SH3 domains. These observations add further support to the concept that Grb2 is a modular adaptor protein. Images PMID:7689150

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

    PubMed Central

    Biocca, S; Cattaneo, A; Calissano, P

    1984-01-01

    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 binding protein after 48 hr of incubation with NGF is potentiated by concomitant treatment of PC12 cells with antimitotic drugs acting at different levels of DNA replication. Purification on a preparative scale of this protein and analysis of its major physicochemical properties show that: (i) it constitutes 0.5% of total soluble proteins of naive PC12 cells; (ii) its molecular weight measured by NaDodSO4/PAGE is Mr 34,000 (sucrose gradient centrifugation under nondenaturing conditions yields a sedimentation coefficient s20,w of 8.1 S, indicating that the native protein is an oligomer); (iii) amino acid analysis demonstrates a preponderance of acidic over basic residues, while electrofocusing experiments show that it has an isoelectric point around 8.0; (iv) approximately 15% of the protein is phosphorylated in vivo. It is postulated that control of the synthesis of this protein is connected with activation of a differentiative program triggered by NGF in the PC12 neoplastic cell line at some step(s) of DNA activity. Images PMID:6585787

  3. Acute and chronic administration of the branched-chain amino acids decreases nerve growth factor in rat hippocampus.

    PubMed

    Scaini, Giselli; Mello-Santos, Lis Mairá; Furlanetto, Camila B; Jeremias, Isabela C; Mina, Francielle; Schuck, Patrícia F; Ferreira, Gustavo C; Kist, Luiza W; Pereira, Talita C B; Bogo, Maurício R; Streck, Emilio L

    2013-12-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase leading to accumulation of the branched-chain amino acids (BCAA) and their corresponding branched-chain α-keto acids. In this study, we examined the effects of acute and chronic administration of BCAA on protein levels and mRNA expression of nerve growth factor (NGF) considering that patients with MSUD present neurological dysfunction and cognitive impairment. Considering previous observations, it is suggested that oxidative stress may be involved in the pathophysiology of the neurological dysfunction of MSUD. We also investigated the influence of antioxidant treatment (N-acetylcysteine and deferoxamine) in order to verify the influence of oxidative stress in the modulation of NGF levels. Our results demonstrated decreased protein levels of NGF in the hippocampus after acute and chronic administration of BCAA. In addition, we showed a significant decrease in the expression of ngf in the hippocampus only following acute administration in 10-day-old rats. Interestingly, antioxidant treatment was able to prevent the decrease in NGF levels by increasing ngf expression. In conclusion, the results suggest that BCAA is involved in the regulation of NGF in the developing rat. Thus, it is possible that alteration of neurotrophin levels during brain maturation could be of pivotal importance in the impairment of cognition provoked by BCAA. Moreover, the decrease in NGF levels was prevented by antioxidant treatment, reinforcing that the hypothesis of oxidative stress can be an important pathophysiological mechanism underlying the brain damage observed in MSUD. PMID:23559405

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

    PubMed

    Abram, Melanie; Wegmann, Michael; Fokuhl, Verena; Sonar, Sanchaita; Luger, Elke Olga; Kerzel, Sebastian; Radbruch, Andreas; Renz, Harald; Zemlin, Michael

    2009-04-15

    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 (NT3) led to a dose-dependent increase in viability of isolated pulmonary plasma cells due to up-regulation of the antiapoptotic Bcl2 pathway. In parallel, the expression of transcription factors that stimulate the production of immunoglobulins (X-box binding protein 1 and NF-kappaB subunit RelA) was enhanced in plasma cells treated with NGF and NT3. These findings were supported in vivo. When the NGF pathway was blocked by intranasal application of a selective TrkA inhibitor, sensitized mice showed reduced numbers of pulmonary plasma cells and developed lower levels of allergen-specific and total serum IgE in response to OVA inhalation. This suggests that in the allergic airway inflammation, NGF/TrkA-mediated pulmonary IgE production contributes significantly to serum-IgE levels. We conclude that the neurotrophins NGF and NT3 act as survival factors for pulmonary plasma cells and thus are important regulators of the local Ab production in the allergic airway disease. PMID:19342646

  5. Evidence for RNA synthesis-dependent and -independent pathways in stimulation of neurite outgrowth by nerve growth factor

    PubMed Central

    Burstein, David E.; Greene, Lloyd A.

    1978-01-01

    Studies on the mechanism of action of nerve growth factor (NGF) were carried out with PC12 rat pheochromocytoma cells. PC12 cells are uniquely useful for such studies because they respond to, but (unlike normal neurons) do not require, NGF and may undergo either generation or regeneration of neurites in response to NGF. Regeneration is defined here as NGF-dependent regrowth of neurites within 24 hr after subculture of NGF-treated PC12 cells. As in cultures of normal NGF-responsive neurons, neurite regeneration by PC12 cells occurs even in the presence of high concentrations of RNA synthesis inhibitors. Generation of neurites is defined as the de novo initiation of outgrowth when PC12 cells are exposed to NGF for the first time. In contrast to regeneration, neurite generation takes place with a lag of at least 24 hr and is blocked by low concentrations of RNA synthesis inhibitors. Such findings suggest that there are both RNA synthesis-dependent and -independent pathways in the mechanism whereby NGF stimulates neurite outgrowth. In addition, NGF-treated PC12 cells undergo a time-dependent loss of the capacity for neurite regeneration after pretreatment with RNA synthesis inhibitors or withdrawal of NGF. Such findings suggest that (i) initiation of neurite outgrowth requires NGF-stimulated, RNA synthesis-dependent accumulation of intracellular material(s), (ii) once such accumulation occurs, RNA synthesis-independent regeneration can occur (but only in the presence of NGF), and (iii) the turnover of such material(s) in the absence of their replacement leads to loss of the capacity for regeneration. A tentative sequence is presented for the events whereby NGF may stimulate neurite outgrowth. PMID:310552

  6. Viral Vector Based Improvement of Optic Nerve Regeneration: Characterization of Individual Axons’ Growth Patterns and Synaptogenesis in a Visual Target

    PubMed Central

    Yungher, Benjamin J.; Luo, Xueting; Salgueiro, Yadira; Blackmore, Murray G.; Park, Kevin K.

    2015-01-01

    Lack of axon growth ability in the central nervous system poses a major barrier to achieving functional connectivity after injury. Thus, a non-transgenic regenerative approach to reinnervating targets has important implications in clinical and research settings. Previous studies using knockout (KO) mice have demonstrated long distance axon regeneration. Using an optic nerve injury model, here we evaluate the efficacy of viral, RNAi and pharmacological approaches that target the PTEN and STAT3 pathways to improve long distance axon regeneration in wild type (WT) mice. Our data show that adeno-associated virus (AAV) expressing short hairpin RNA (shRNA) against PTEN (shPTEN) enhances retinal ganglion cell axon regeneration after crush injury. However, compared to the previous data in PTEN KO mice, AAV-shRNA results in a lesser degree of regeneration, likely due to incomplete gene silencing inherent to RNAi. In comparison, an extensive enhancement in regeneration is seen when AAV-shPTEN is coupled to AAV encoding ciliary neurotrophic factor (CNTF) and to a cyclic adenosine monophosphate (cAMP) analogue, allowing axons to travel long distances and reach their target. We apply whole tissue imaging that facilitates three-dimensional visualization of single regenerating axons and document heterogeneous terminal patterns in the targets. This shows that some axonal populations generate extensive arbors and make synapses with the target neurons. Collectively, we show a combinatorial viral RNAi and pharmacological strategy that improves long distance regeneration in WT animals and provide single fiber projection data that indicates a degree of preservation of target recognition. PMID:26005861

  7. Longitudinal Changes in Retinal Nerve Fiber Layer Thickness after Intravitreal Anti-vascular Endothelial Growth Factor Therapy

    PubMed Central

    Jo, Young-Joon; Kim, Woo-Jin; Shin, Il-Hwan

    2016-01-01

    Purpose To determine the effects of intravitreal anti-vascular endothelial growth factor (VEGF) on thickness of the retinal nerve fiber layer (RNFL) in patients with age-related macular degeneration. Methods Twenty eyes of 20 patients diagnosed with age-related macular degeneration who underwent intravitreal anti-VEGF injection were studied. Postinjection RNFL thickness was measured using optical coherence tomography. Average thickness, four-quadrant RNFL thicknesses, and intraocular pressure (IOP) in affected eyes were measured before and 6 and 12 months after anti-VEGF injection for comparison. RNFL thickness and IOP in affected and normal fellow eyes were also compared. Given that macular lesions can affect RNFL thickness, the changes in thickness were evaluated by dividing the 12 clock-hour RNFL into the pathologic areas adjacent to the lesion and the non-pathologic area. Results The mean clock-hour segment in the pathologic area was 4.8 hours. A significantly thicker RNFL was exhibited in temporal quadrants and pathologic areas (p = 0.043 and 0.048, respectively) in affected eyes before injection compared to the baseline RNFL thickness in normal eyes. No significant differences were found in RNFL thickness or IOP between affected and normal eyes after injection. The changes over time in the temporal and pathologic areas were statistically significant at 6 and 12 months after injection compared to baseline data (p < 0.05). No significant differences were displayed in RNFL thickness in the other three quadrants or in non-pathologic areas in either affected or normal eyes. Sequential changes in RNFL thickness in affected eyes were not significant. Conclusions Repeat intravitreal anti-VEGF treatment did not have a significant effect on RNFL thickness. RNFL thickness significantly decreased with time in the pathologic areas and in the temporal segment adjacent to exudative macular lesions. The reduction in RNFL thickness was most likely associated with changes in

  8. Human HOXB cluster and the nerve growth factor receptor gene: Comparison with an orthologous chromosomal domain in mouse

    SciTech Connect

    Bentley, K.L.; Bradshaw, M.S.; Ruddle, F.H.

    1995-11-01

    The structural organization and nucleotide sequence similarity of mammalian Antennapedia-class homeobox genes support the view that the four homeobox clusters (HOXA, B,C, and D on human chromosomes 7, 17, 12 and 2, respectively) arose through a combination of gene duplication and divergence to form a cluster, followed by several cluster duplications. The duplication events that gave rise to the four clusters appear to have involved chromosomal domains extending well beyond the borders of the clusters in either direction. This evidence arises from the observation that many genes closely linked to the homeobox clusters on different chromosomes show sequence similarity. Here, we present a continuation of physical mapping studies to determine the extent and organization of the duplicated regions surrounding the four homeobox clusters in human. Southern blots prepared from pulsed-field gels of human DNA were probed with cloned segments of human HOXB genes and the nerve growth factor receptor (NGFR) gene on chromosome 17q21-q22. Restriction enzyme analysis revealed the close physical linkage of these genes within 100 kb. Two yeast artificial chromosomes (YACs), 220 and 380 kb in size, were isolated using oligonucleotide primers specific for NGFR. Both YACs contained the entire HOXB cluster. Restriction mapping of the clones indicated that the distance separating these loci could not be greater than 50 kb. This result confirms and extends previous information on the proximity of these genes as determined by genetic linkage analysis and closely parallels the orthologous loci in the mouse. 48 refs., 4 figs., 1 tab.

  9. Muscle-targeted hydrodynamic gene introduction of insulin-like growth factor-1 using polyplex nanomicelle to treat peripheral nerve injury.

    PubMed

    Nagata, Kazuya; Itaka, Keiji; Baba, Miyuki; Uchida, Satoshi; Ishii, Takehiko; Kataoka, Kazunori

    2014-06-10

    The recovery of neurologic function after peripheral nerve injury often remains incomplete because of the prolonged reinnervation process, which leads to skeletal muscle atrophy and articular contracture from disuse over time. To rescue the skeletal muscle and promote functional recovery, insulin-like growth factor-1 (IGF-1), a potent myogenic factor, was introduced into the muscle by hydrodynamic injection of IGF-1-expressing plasmid DNA using a biocompatible nonviral gene carrier, a polyplex nanomicelle. In a mouse model of sciatic nerve injury, the introduction of IGF-1 into the skeletal muscle of the paralyzed limb effectively alleviated a decrease in muscle weight compared with that in untreated control mice. Histologic analysis of the muscle revealed the IGF-1-expressing plasmid DNA (pDNA) to have a myogenic effect, inducing muscle hypertrophy with the upregulation of the myogenic regulatory factors, myogenin and MyoD. The evaluation of motor function by walking track analysis revealed that the group that received the hydrodynamic injection of IGF-1-expressing pDNA using the polyplex nanomicelle had significantly early recovery of motor function compared with groups receiving negative control pDNA and untreated controls. Early recovery of sensation in the distal area of sciatic nerve injury was also induced by the introduction of IGF-1-expressing pDNA, presumably because of the effect of secreted IGF-1 protein in the vicinity of the injured sciatic nerve exerting a synergistic effect with muscle hypertrophy, inducing a more favorable prognosis. This approach of introducing IGF-1 into skeletal muscle is promising for the treatment of peripheral nerve injury by promoting early motor function recovery. PMID:24657809

  10. Nerve biopsy

    MedlinePlus

    ... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Update Date 6/1/2015 ...

  11. Nerve conduction

    MedlinePlus Videos and Cool Tools

    ... the spinal cord to muscles and sensory receptors. A peripheral nerve is composed of nerve bundles (fascicles) ... two neurons, it must first be converted to a chemical signal, which then crosses a space of ...

  12. Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth.

    PubMed

    Zhuang, Hai; Bu, Shoushan; Hua, Lei; Darabi, Mohammad A; Cao, Xiaojian; Xing, Malcolm

    2016-01-01

    In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide(®)). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group (P>0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable

  13. Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

    PubMed Central

    Zhuang, Hai; Bu, Shoushan; Hua, Lei; Darabi, Mohammad A; Cao, Xiaojian; Xing, Malcolm

    2016-01-01

    In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide®). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group (P>0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable

  14. Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

    PubMed

    Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

    2013-02-01

    Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. PMID:23152192

  15. Binding, internalization, and retrograde transport of /sup 125/I-nerve growth factor in cultured rat sympathetic neurons

    SciTech Connect

    Claude, P.; Hawrot, E.; Dunis, D.A.; Campenot, R.B.

    1982-01-01

    Sympathetic neurons internalize nerve growth factor (NGF) and transport it retrogradely to their cell bodies where it appears to serve a trophic function in maintaining neuronal survival. We have characterized the binding, internalization, and retrograde transport of /sup 125/I-NGF by cultured rat sympathetic neurons. After 3 to 4 weeks in culture, sympathetic neurons possessed approximately 2 X 10(7) specific, cell surface NGF binding sites per neuron with an apparent affinity constant of 2 to 5 X 10(9) M. The density of binding sites on the plasma membrane of the neurites approximately twice that on the plasma membrane of the cell bodies. Because of the extensive network of neuronal processes, the neurites probably account for more than 99.5% of the total binding in mature cultures. Using electron microscope autoradiography, we localized the distribution of /sup 125/I-NGF in the cell body following a 1-hr exposure to /sup 125/I-NGF. The majority of silver grains were associated with lysosomal organelles, including secondary lysosomes, residual bodies, and multivesicular bodies (MVB). The MVB were the most heavily labeled, with a labeling density (L.D.) of 21, while the lysosomes had a L.D. of 3.1. To study the retrograde transport of /sup 125/I-NGF, neurons were grown in compartmentalized culture dishes and their distal processes were exposed to /sup 125/I-NGF. Radioactive material was transported to the cell bodies at the rate of approximately 3 mm/hr. The transport mechanism was sensitive to colchicine and was saturable with respect to NGF. After 8 hr of transport, when the radioactivity in the cell bodies had reached a steady state, the label again was localized primarily to the MVB (L.D. . 16.8) and the lysosomes (L.D. . 3.8). The nuclei were not labeled significantly and had an overall L.D. of 0.47. We saw no evidence for the accumulation of NGF by the nuclear membrane, the nucleolus, or chromatin.

  16. Oral Haloperidol or Risperidone Treatment in Rats: Temporal Effects on Nerve Growth Factor Receptors, Cholinergic Neurons, and Memory Performance

    PubMed Central

    Terry, Alvin V.; Gearhart, Debra A.; Warner, Samantha E.; Zhang, Guodong; Bartlett, Michael G.; Middlemore, Mary-Louise; Beck, Wayne D.; Mahadik, Sahebarao P.; Waller, Jennifer L.

    2007-01-01

    First and second generation antipsychotics (FGAs and SGAs) ameliorate psychotic symptoms of schizophrenia, however, their chronic effects on information processing and memory function (i.e., key determinants of long term functional outcome) are largely unknown. In this rodent study the effects of different time periods (ranging from two weeks to six months) of oral treatment with the FGA, haloperidol (2.0 mg/kg/day), or the SGA, risperidone (2.5 mg/kg/day) on a water maze repeated acquisition procedure, the levels of nerve growth factor receptors, and two important cholinergic proteins, the vesicular acetylcholine transporter and the high affinity choline transporter were evaluated. The effects of the antipsychotics on a spontaneous novel object recognition procedure were also assessed during days 8-14 and 31-38 of treatment. Haloperidol (but not risperidone) was associated with impairments in water maze hidden platform trial performance at each of the time periods evaluated up to 45 days, but not when tested during days 83-90. In contrast, risperidone did not impair water maze task performance at the early time periods and it was actually associated with improved performance during the 83-90 day period. Both antipsychotics, however, were associated with significant water maze impairments during the 174-180 day period. Further, haloperidol was associated with decrements in short delay performance in the spontaneous novel object recognition task during both the 8-14 and 31-38 periods of treatment, while risperidone was associated with short delay impairment during the 31-38 day time period. Both antipsychotics were also associated with time dependent alterations in the vesicular acetylcholine transporter, the high affinity choline transporter, as well as TrkA, and p75 neurotrophin receptors in specific brain regions. These data support the notion that while risperidone may hold some advantages over haloperidol, both antipsychotics can produce time

  17. Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine

    PubMed Central

    Coskun, Salih; Varol, Sefer; Ozdemir, Hasan H; Agacayak, Elif; Aydın, Birsen; Kapan, Oktay; Camkurt, Mehmet Akif; Tunc, Saban; Cevik, Mehmet Ugur

    2016-01-01

    Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case–control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls) for the following polymorphisms: rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C) in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and rs4839435(G/A) in the NGF gene using 5′-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] =0.723 [0.523–0.999]). Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT genotype of rs6330 in NGF was significantly higher in MA patients than in MO patients (P=0.036) or healthy controls (P=0.026), and this disappeared after correction for multiple testing. Also, the rs6330*T minor allele was more common in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] =1.626 [1.117–2.365] or P=0.007, ORs [95% CIs] =1.610 [1.140–2.274], respectively). In conclusion, this is the first clinical study to evaluate the association between BDNF and NGF polymorphisms in migraine patients compared with health controls. Our findings suggest that the NGF rs6330*T minor allele might be nominated as a risk

  18. Bridging Grafts and Transient Nerve Growth Factor Infusions Promote Long-Term Central Nervous System Neuronal Rescue and Partial Functional Recovery

    NASA Astrophysics Data System (ADS)

    Tuszynski, Mark H.; Gage, Fred H.

    1995-05-01

    Grafts of favorable axonal growth substrates were combined with transient nerve growth factor (NGF) infusions to promote morphological and functional recovery in the adult rat brain after lesions of the septohippocampal projection. Long-term septal cholinergic neuronal rescue and partial hippocampal reinnervation were achieved, resulting in partial functional recovery on a simple task assessing habituation but not on a more complex task assessing spatial reference memory. Control animals that received transient NGF infusions without axonal-growth-promoting grafts lacked behavioral recovery but also showed long-term septal neuronal rescue. These findings indicate that (i) partial recovery from central nervous system injury can be induced by both preventing host neuronal loss and promoting host axonal regrowth and (ii) long-term neuronal loss can be prevented with transient NGF infusions.

  19. Nerve Growth Factor Stimulates Interaction of Cayman Ataxia Protein BNIP-H/Caytaxin with Peptidyl-Prolyl Isomerase Pin1 in Differentiating Neurons

    PubMed Central

    Buschdorf, Jan Paul; Chew, Li Li; Soh, Unice Jim Kim; Liou, Yih-Cherng; Low, Boon Chuan

    2008-01-01

    Mutations in ATCAY that encodes the brain-specific protein BNIP-H (or Caytaxin) lead to Cayman cerebellar ataxia. BNIP-H binds to glutaminase, a neurotransmitter-producing enzyme, and affects its activity and intracellular localization. Here we describe the identification and characterization of the binding between BNIP-H and Pin1, a peptidyl-prolyl cis/trans isomerase. BNIP-H interacted with Pin1 after nerve growth factor-stimulation and they co-localized in the neurites and cytosol of differentiating pheochromocytoma PC12 cells and the embryonic carcinoma P19 cells. Deletional mutagenesis revealed two cryptic binding sites within the C-terminus of BNIP-H such that single point mutants affecting the WW domain of Pin1 completely abolished their binding. Although these two sites do not contain any of the canonical Pin1-binding motifs they showed differential binding profiles to Pin1 WW domain mutants S16E, S16A and W34A, and the catalytically inert C113A of its isomerase domain. Furthermore, their direct interaction would occur only upon disrupting the ability of BNIP-H to form an intramolecular interaction by two similar regions. Furthermore, expression of Pin1 disrupted the BNIP-H/glutaminase complex formation in PC12 cells under nerve growth factor-stimulation. These results indicate that nerve growth factor may stimulate the interaction of BNIP-H with Pin1 by releasing its intramolecular inhibition. Such a mechanism could provide a post-translational regulation on the cellular activity of BNIP-H during neuronal differentiation. (213 words) PMID:18628984

  20. Reduced density of neuropeptide Y neurons in the somatosensory cortex of old male and female rats: relation to cholinergic depletion and recovery after nerve growth factor treatment.

    PubMed

    Cardoso, A; Paula-Barbosa, M M; Lukoyanov, N V

    2006-02-01

    Synthesis of neuropeptide Y in the neocortex and activity of the basalocortical cholinergic system are both reduced in the aging brain. We hypothesized that, by stimulating the activity of the basal forebrain cholinergic neurons, nerve growth factor might also be capable of restoring the synthesis of neuropeptide Y in cortical neurons. Old male and female rats were intraventricularly infused with nerve growth factor for 14 days and their brains were analyzed in order to quantify the densities of neuropeptide Y-immunoreactive neurons and of fiber varicosities stained for vesicular acetylcholine transporter protein in layers II/III, V and VI of the primary somatosensory barrel-field cortex. The areal densities of neuropeptide Y neurons and of vesicular acetylcholine transporter protein varicosities in all cortical laminae were found to be dramatically decreased in old rats when compared with young rats. However, infusions of nerve growth factor, known to exert a powerful trophic effect upon cortically projecting cholinergic neurons, have led to considerable recovery of vesicular acetylcholine transporter protein-positive terminal fields, which was paralleled by complete restoration of function in neuropeptide Y-producing neurons. With respect to the gender differences, although the density of cortical neuropeptide Y neurons was found to be significantly higher in young females than in young males and the opposite was true for vesicular acetylcholine transporter protein-positive varicosities, the general pattern of age- and treatment-related changes in these neurochemical markers was similar in both sexes. Overall, the age- and treatment-related variations in the density of cortical neuropeptide Y cells were found to correlate with those observed in the density of vesicular acetylcholine transporter protein varicosities. These results lend support to the idea that there is a causal relationship between age-related changes in cortical cholinergic and neuropeptide Y

  1. Plasticity of Mesenchymal Stem Cells from Mouse Bone Marrow in the Presence of Conditioned Medium of the Facial Nerve and Fibroblast Growth Factor-2

    PubMed Central

    Lucena, Eudes Euler de Souza; Guzen, Fausto Pierdoná; Cavalcanti, José Rodolfo Lopes de Paiva; Marinho, Maria Jocileide de Medeiros; Pereira, Wogelsanger Oliveira; Barboza, Carlos Augusto Galvão; Costa, Miriam Stela Mariz de Oliveira; Júnior, Expedito Silva do Nascimento; Cavalcante, Jeferson Sousa

    2014-01-01

    A number of evidences show the influence of the growth of injured nerve fibers in peripheral nervous system as well as potential implant stem cells (SCs). The SCs implementation in the clinical field is promising and the understanding of proliferation and differentiation is essential. This study aimed to evaluate the plasticity of mesenchymal SCs from bone marrow of mice in the presence of culture medium conditioned with facial nerve explants and fibroblast growth factor-2 (FGF-2). The growth and morphology were assessed for over 72 hours. Quantitative phenotypic analysis was taken from the immunocytochemistry for glial fibrillary acidic protein (GFAP), protein OX-42 (OX-42), protein associated with microtubule MAP-2 (MAP-2), protein β-tubulin III (β-tubulin III), neuronal nuclear protein (NeuN), and neurofilament 200 (NF-200). Cells cultured with conditioned medium alone or combined with FGF-2 showed morphological features apparently similar at certain times to neurons and glia and a significant proliferative activity in groups 2 and 4. Cells cultivated only with conditioned medium acquired a glial phenotype. Cells cultured with FGF-2 and conditioned medium expressed GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200. This study improves our understanding of the plasticity of mesenchymal cells and allows the search for better techniques with SCs. PMID:25614888

  2. Do growth-stimulated retinal ganglion cell axons find their central targets after optic nerve injury? New insights by three-dimensional imaging of the visual pathway.

    PubMed

    Diekmann, Heike; Leibinger, Marco; Fischer, Dietmar

    2013-10-01

    Retinal ganglion cells (RGCs) do not normally regenerate injured axons. However, several strategies to transform RGCs into a potent regenerative state have been developed in recent years. Intravitreal CNTF application combined with conditional PTEN and SOCS3 deletion or zymosan-induced inflammatory stimulation together with cAMP analogue injection and PTEN-deletion in RGCs induce long-distance regeneration into the optic nerve of adult mice. A recent paper by the Benowitz group (de Lima et al.) claimed that the latter treatment enables full-length regeneration, with axons correctly navigating to their central target zones and partial recovery of visual behaviors. To gain a more detailed view of the extent and the trajectories of regenerating axons, Luo et al. applied a tissue clearing method and fluorescent microscopy to allow the tracing of naïve and regenerating RGC axons in whole ON and all the way to their brain targets. Using this approach, the authors found comparable axon regeneration in the optic nerve after both above-mentioned experimental treatments. Regeneration was accompanied by prevalent aberrant axon growth in the optic nerve and significant axonal misguidance at the optic chiasm. Less than 120 axons per animal reached the optic chiasm and only few entered the correct optic tract. Importantly, no axons reached visual targets in the olivary pretectal nucleus, the lateral geniculate nucleus or the superior colliculus, thereby contradicting and challenging previous claims by the Benowitz group. The data provided by Luo et al. rather suggest that potent stimulation of axonal growth per se is insufficient to achieve functional recovery and underscore the need to investigate regeneration-relevant axon guidance mechanisms in the mature visual system. PMID:23816572

  3. A Comparison Study of Growth Factor Expression following Treatment with Transcutaneous Electrical Nerve Stimulation, Saline Solution, Povidone-Iodine, and Lavender Oil in Wounds Healing

    PubMed Central

    Koca Kutlu, Adalet; Çeçen, Dilek; Gürgen, Seren Gülşen; Sayın, Oya; Çetin, Ferihan

    2013-01-01

    This study compared the effects of transcutaneous electrical nerve stimulation (TENS), saline solution (SS), povidone-iodine (PI), and lavender oil (Lavandula angustifolia) through expression of growth factors in a rat model of wound healing. Six experimental groups were established, each containing 8 rats: a healthy group with no incision wounds, an incision-control group, an incision and TENS group, an incision and SS group, an incision and PI group, and an incision and lavender oil group. Experiments continued for 5 days, after which the skin in the excision area was removed. Tissue concentrations of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-A were measured using enzyme-linked immunosorbent assay (ELISA). Tissue expressions of EGF, PDGF-A, and fibroblast growth factor (FGF)-2 were determined using immunohistochemistry. Wound closure progressed more rapidly in the TENS and lavender oil groups than in the control and other study groups. In particular, PDGF-A expressions in the dermis and EGF expression in the epidermis were significantly intense in the TENS group (P < 0.05). In addition, ELISA levels of growth factors such as PDGF-A and EGF were significantly higher in TENS group compared to the control group (P < 0.05). These immunohistochemical and ELISA results suggest that TENS may improve wound healing through increasing growth factors in the dermis and epidermis more than other topical applications. PMID:23861704

  4. A novel method for inducing nerve growth via modulation of host resting potential: gap junction-mediated and serotonergic signaling mechanisms.

    PubMed

    Blackiston, Douglas J; Anderson, George M; Rahman, Nikita; Bieck, Clara; Levin, Michael

    2015-01-01

    A major goal of regenerative medicine is to restore the function of damaged or missing organs through the implantation of bioengineered or donor-derived components. It is necessary to understand the signals and cues necessary for implanted structures to innervate the host, as organs devoid of neural connections provide little benefit to the patient. While developmental studies have identified neuronal pathfinding molecules required for proper patterning during embryogenesis, strategies to initiate innervation in structures transplanted at later times or alternate locations remain limited. Recent work has identified membrane resting potential of nerves as a key regulator of growth cone extension or arrest. Here, we identify a novel role of bioelectricity in the generation of axon guidance cues, showing that neurons read the electric topography of surrounding cells, and demonstrate these cues can be leveraged to initiate sensory organ transplant innervation. Grafts of fluorescently labeled embryological eye primordia were used to produce ectopic eyes in Xenopus laevis tadpoles. Depolarization of host tissues through anion channel activation or other means led to a striking hyperinnervation of the body by these ectopic eyes. A screen of possible transduction mechanisms identified serotonergic signaling to be essential for hyperinnervation to occur, and our molecular data suggest a possible model of bioelectrical control of the distribution of neurotransmitters that guides nerve growth. Together, these results identify the molecular components of bioelectrical signaling among cells that regulates axon guidance, and suggest novel biomedical and bioengineering strategies for triggering neuronal outgrowth using ion channel drugs already approved for human use. PMID:25449797

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

    SciTech Connect

    Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

    2010-07-16

    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.

  6. Impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain

    PubMed Central

    Ding, Yuanyuan; Wang, Zhibin; Ma, Jiaming; Hong, Tao; Zhu, Yongqiang; Li, Hongxi; Pan, Shinong

    2016-01-01

    Objective To investigate the impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of μ-opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain. Methods The rats were randomly grouped and then injected with 10 μl of phosphate buffer saline or Walker256 tumor cells into the upper segment of left tibia. Thirteen days after the injection, the intrathecal catheterization was performed, followed by the injection of saline, anti-nerve growth factor, nerve growth factor, and naloxone twice a day. The pain ethological changes were measured at the set time points; the expression changes of μ-opioid receptor protein and mRNA in spinal dorsal horn and dorsal root ganglia were detected on the 18th day. Results After the tumor cells were injected into the tibia, hyperalgesia appeared and the expression of μ-opioid receptor protein and mRNA in spinal dorsal horn and dorsal root ganglia was increased, compared with the sham group; after intrathecally injected anti-nerve growth factor, the significant antinociceptive effects appeared, and the μ-opioid receptor expression was increased, compared with the cancer pain group; the μ-opioid receptor expressions in the other groups showed no statistical significance. The naloxone pretreatment could mostly inverse the antinociception effects of anti-nerve growth factor. Conclusions Anti-nerve growth factor could reduce hyperalgesia in the cancer-induced bone pain rats, and the antinociceptive effects were related with the upregulation of μ-opioid receptor. PMID:27118770

  7. In vitro and in vivo gene therapy with CMV vector-mediated presumed dog beta-nerve growth factor in pyridoxine-induced neuropathy dogs.

    PubMed

    Chung, Jin Young; Choi, Jung Hoon; Shin, Il Seob; Choi, Eun Wha; Hwang, Cheol Yong; Lee, Sang Koo; Youn, Hwa Young

    2008-12-01

    Due to the therapeutic potential of gene therapy for neuronal injury, many studies of neurotrophic factors, vectors, and animal models have been performed. The presumed dog beta-nerve growth factor (pdbeta-NGF) was generated and cloned and its expression was confirmed in CHO cells. The recombinant pdbeta-NGF protein reacted with a human beta-NGF antibody and showed bioactivity in PC12 cells. The pdbeta-NGF was shown to have similar bioactivity to the dog beta-NGF. The recombinant pdbeta-NGF plasmid was administrated into the intrathecal space in the gene therapy group. Twenty-four hours after the vector inoculation, the gene therapy group and the positive control group were intoxicated with excess pyridoxine for seven days. Each morning throughout the test period, the dogs' body weight was taken and postural reaction assessments were made. Electrophysiological recordings were performed twice, once before the experiment and once after the test period. After the experimental period, histological analysis was performed. Dogs in the gene therapy group had no weight change and were normal in postural reaction assessments. Electrophysiological recordings were also normal for the gene therapy group. Histological analysis showed that neither the axons nor the myelin of the dorsal funiculus of L4 were severely damaged in the gene therapy group. In addition, the dorsal root ganglia of L4 and the peripheral nerves (sciatic nerve) did not experience severe degenerative changes in the gene therapy group. This study is the first to show the protective effect of NGF gene therapy in a dog model. PMID:19043311

  8. Lysine-doped polypyrrole/spider silk protein/poly(l-lactic) acid containing nerve growth factor composite fibers for neural application.

    PubMed

    Zhang, Hong; Wang, Kefeng; Xing, Yiming; Yu, Qiaozhen

    2015-11-01

    Lysine-doped polypyrrole (PPy)/regenerated spider silk protein (RSSP)/poly(l-lactic) acid (PLLA)/nerve growth factor (NGF) (L-PRPN) composite scaffold was fabricated by co-axial electrospraying and electrospinning. This L-PRPN composite scaffold had a structure of microfibers with a core-shell structure as the stems and nanofibers as branches. Assessment in vitro demonstrated that the L-PRPN composite micro/nano-fibrous scaffold could maintain integrated structure for at least 4months and the pH value of PBS at about 7.28. It had good biocompatibility and cell adhesion and relatively stable conductivity. PC 12 cells cultured on this scaffold, anisotropic cell-neurite-cell-neurite or neurite-neurite sheets were formed after being cultured for 6days. Evaluations in vivo also showed that L-PRPN composite fibrous conduit was effective at bridging 2.0cm sciatic nerve gap in adult rat within 10months. This conduit and electrical stimulation (ES) through it promoted Schwann cell migration and axonal regrowth. PMID:26249628

  9. Gelatin Nanostructured Lipid Carriers Incorporating Nerve Growth Factor Inhibit Endoplasmic Reticulum Stress-Induced Apoptosis and Improve Recovery in Spinal Cord Injury.

    PubMed

    Zhu, Si-Pin; Wang, Zhou-Guang; Zhao, Ying-Zheng; Wu, Jiang; Shi, Hong-Xue; Ye, Li-Bing; Wu, Fen-Zan; Cheng, Yi; Zhang, Hong-Yu; He, Songbin; Wei, Xiaojie; Fu, Xiao-Bing; Li, Xiao-Kun; Xu, Hua-Zi; Xiao, Jian

    2016-09-01

    Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3β and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3β and ERK1/2. PMID:26232067

  10. Cross talk among tyrosine kinase receptors in PC12 cells: desensitization of mitogenic epidermal growth factor receptors by the neurotrophic factors, nerve growth factor and basic fibroblast growth factor.

    PubMed Central

    Mothe, I; Ballotti, R; Tartare, S; Kowalski-Chauvel, A; Van Obberghen, E

    1993-01-01

    We have studied the effects of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) on epidermal growth factor (EGF) binding to PC12 cells. We show that NGF and bFGF rapidly induce a reduction in 125I-EGF binding to PC12 cells in a dose-dependent manner. This decrease amounts to 50% for NGF and 35% for bFGF. Both factors appear to act through a protein kinase C(PKC)-independent pathway, because their effect persists in PKC-downregulated PC12 cells. Scatchard analysis indicates that NGF and bFGF decrease the number of high affinity EGF binding sites. In addition to their effect on EGF binding, NGF and bFGF activate in intact PC12 cells one or several serine/threonine kinases leading to EGF receptor threonine phosphorylation. Using an in vitro phosphorylation system, we show that NGF- or bFGF-activated extracellular regulated kinase 1 (ERK1) is able to phosphorylate a kinase-deficient EGF receptor. Phosphoamino acid analysis indicates that this phosphorylation occurs mainly on threonine residues. Furthermore, two comparable phosphopeptides are observed in the EGF receptor, phosphorylated either in vivo after NGF treatment or in a cell-free system by NGF-activated ERK1. Finally, a good correlation was found between the time courses of ERK1 activation and 125I-EGF binding inhibition after NGF or bFGF treatment. In conclusion, in PC12 cells the NGF- and bFGF-stimulated ERK1 appears to be involved in the induction of the threonine phosphorylation of the EGF receptor and the decrease in the number of high affinity EGF binding sites. Images PMID:8400459

  11. An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

    PubMed Central

    Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

    2015-01-01

    Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons. PMID:26200940

  12. HemoHIM improves ovarian morphology and decreases expression of nerve growth factor in rats with steroid-induced polycystic ovaries.

    PubMed

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Bae, Chun Sik; Park, Hae Ran; Jung, Uhee; Jo, Sung Kee

    2009-12-01

    Estradiol valerate (EV)-induced polycystic ovaries (PCOs) in rats cause the anovulation and cystic ovarian morphology. We investigated whether treatment with HemoHIM influences the ovarian morphology and the expression of nerve growth factor (NGF) in an EV-induced PCO rat model. PCO was induced by a single intramuscular injection of EV (4 mg, dissolved in sesame oil) in adult cycling rats. HemoHIM was either administered orally (100 mg/kg of body weight/day) for 35 consecutive days or injected intraperitoneally (50 mg/kg of body weight) every other day after EV injection. Ovarian morphology was almost normalized, and NGF was normalized in the PCO + HemoHIM group. HemoHIM lowered the high numbers of antral follicles and increased the number of corpora lutea in PCOs. The results are consistent with a beneficial effect of HemoHIM in the prevention and treatment of PCO syndrome. PMID:20041792

  13. A conjugate composed of nerve growth factor coupled to a non-toxic derivative of Clostridium botulinum neurotoxin type A can inhibit neurotransmitter release in vitro.

    PubMed

    Chaddock, J A; Purkiss, J R; Duggan, M J; Quinn, C P; Shone, C C; Foster, K A

    2000-01-01

    Nerve growth factor (NGF) receptor binding, internalisation and transportation of NGF has been identified as a potential route of delivery for other molecules. A derivative of Clostridium botulinum neurotoxin type A (LHN) that retains catalytic activity but has significantly reduced cell-binding capability has been prepared and chemically coupled to NGF. Intact clostridial neurotoxins potently inhibit neurotransmitter release at the neuromuscular junction by proteolysis of specific components of the vesicle docking/fusion complex. Here we report that the NGF-LHN/A conjugate, when applied to PC12 cells, significantly inhibited neurotransmitter release and cleaved the type A toxin substrate. This work represents the successful use of NGF as a targeting moiety for the delivery of a neurotoxin fragment. PMID:11019785

  14. Induction of rapid eye movement sleep by the microinjection of nerve growth factor into the pontine reticular formation of the cat.

    PubMed

    Yamuy, J; Morales, F R; Chase, M H

    1995-05-01

    Nerve growth factor is an endogenous protein which belongs to the neurotrophin family of trophic factors. According to the neurotrophic hypothesis, neurotrophins are synthetized by target tissues and regulate the survival and phenotype of their innervating neurons. Whereas these trophic molecules have been mainly thought to be involved in developmental processes, their existence in the central nervous system of the adult animal suggests that they may play a role in neuronal physiology. Recently, it has been reported that neurons that express messenger RNA for two neurotrophins, namely brain-derived neurotrophic factor and neurotrophin-3, are located medial to the locus coeruleus and ventral to the fourth ventricle. This area corresponds to the latero-dorsal tegmental nucleus, which contains cholinergic neurons that have been implicated in the generation of rapid eye movement sleep. In turn, the laterodorsal tegmental nucleus is reciprocally connected with the nucleus pontis oralis in the rostrodorsal pontine reticular formation, which is an area that is involved in the initiation of the physiological patterns of activity that define the state of rapid eye movement sleep. Scattered neurons in the nucleus pontis oralis express the low-affinity nerve growth factor receptor which also binds the other neurotrophins with similar affinity. In addition, neurons in the area of the nucleus pontis oralis have been reported to express a subtype of the neurotrophin high affinity receptors. These membrane receptors, independently or in combination with the low affinity receptors, have been proposed to mediate the delayed, long-term effects of neurotrophins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7637879

  15. (-)-Epigallocatechin-3-Gallate Modulates Spinal Cord Neuronal Degeneration by Enhancing Growth-Associated Protein 43, B-Cell Lymphoma 2, and Decreasing B-Cell Lymphoma 2-Associated X Protein Expression after Sciatic Nerve Crush Injury

    PubMed Central

    Al-Maghrebi, May; Rao, Muddanna S.; Khraishah, Haitham

    2015-01-01

    Abstract Our previous studies have established that (-)-epigallocatechin-3-gallate (EGCG) has both neuroprotective and -regenerative capacity after sciatic nerve injury. Moreover, this improvement was evident on the behavioral level. The aim of this study was to investigate the central effects of ECGC on spinal cord motor neurons after sciatic nerve injury. Our study showed that administering 50 mg/kg intraperitoneally i.p. of EGCG to sciatic nerve-injured rats improved their performance on different motor functions and mechanical hyperesthesia neurobehavioral tests. Histological analysis of spinal cords of EGCG-treated sciatic nerve-injured (CRUSH+ECGC) animals showed an increase in the number of neurons in the anterior horn, when compared to the naïve, sham, and saline-treated sciatic nerve-injured (CRUSH) control groups. Additionally, immunohistochemical study of spinal cord sections revealed that EGCG reduced the expression of glial fibrillary acidic protein and increased the expression of growth-associated protein 43, a marker of regenerating axons. Finally, EGCG reduced the ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 and increased the expression of survivin gene. This study may shed some light on the future clinical use of EGCG and its constituents in the treatment of peripheral nerve injury. PMID:25025489

  16. Photoreceptor-specific protein expression of mouse retina in organ culture and retardation of rd degeneration in vitro by a combination of basic fibroblast and nerve growth factors.

    PubMed

    Caffé, A R; Söderpalm, A; van Veen, T

    1993-08-01

    Previously we have presented the morphological features of a neonatal mouse retinal explant kept in culture for 3 to 4 weeks. To further evaluate the organotypic parameters of the tissue we have examined the presence of opsin, S-antigen, and interphotoreceptor retinoid-binding protein (IRBP) in the same experimental paradigm, using light microscopic immunocytochemistry. In vitro, opsin and S-antigen staining is found in photoreceptor somata from genetically normal explants and those derived from mice with the rd or the rds mutation. When present, inner and outer segments label more intensely. No IRBP staining has been found in cell bodies of any genotype. However, some labeling is found in the plexiform layers and in the inner segments. The results indicate that photoreceptor proteins are continuously produced in vitro. This further establishes the organotypic nature of the retinal explant in culture. The administration of growth factors to these explants has been investigated. Neither basic fibroblast growth factor nor nerve growth factor alone has affected the explants phenotype. However, the combination of these proteins has significantly retarded rd cell loss in vitro. PMID:8222732

  17. Sildenafil promotes smooth muscle preservation and ameliorates fibrosis through modulation of extracellular matrix and tissue growth factor gene expression after bilateral cavernosal nerve resection in the rat

    PubMed Central

    Sirad, Fara; Hlaing, Su; Kovanecz, Istvan; Artaza, Jorge N.; Garcia, Leah A.; Rajfer, Jacob; Ferrini, Monica G.

    2010-01-01

    Introduction It has been shown that PDE 5 inhibitors preserve smooth muscle (SM) content and ameliorate the fibrotic degeneration normally seen in the corpora cavernosa after bilateral cavernosal nerve resection (BCNR). However, the downstream mechanisms by which these drugs protect the corpora cavernosa remain poorly understood. Aim To provide insight into the mechanism, we aimed to determine the gene expression profile of angiogenesis related pathways within the penile tissue after BCNR with or without continuous sildenafil treatment. Methods 5-month old Fisher rats were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/Kg. B.W drinking water) for 3 days or 45 days (n=8 rats per group). Total RNAs isolated from the denuded penile shaft and prostate were subjected to reverse transcription and to angiogenesis real time-PCR arrays (84 genes). Changes in protein expression of selected genes such as epiregulin and CTGF were corroborated by western blot and immunohistochemistry. Main outcomes measures Genes modulated by BCNR and sildenafil treatment. Results A decreased expression of genes related to SM growth factors such as epiregulin (EREG), platelet derived growth factor (PDGF), extracellular matrix regulators such as metalloproteinases 3 and 9, endothelial growth factors, together with an up-regulation of pro-fibrotic genes such as connective tissue growth factor (CTGF) and TGFβ2 were found at both time points after BCNR. Sildenafil treatment reversed this process by up-regulating endothelial and SM growth factors and down-regulating pro-fibrotic factors. Sildenafil did not affect the expression of EREG, VEGF, PDGF in the ventral prostate of BCNR animals Conclusions Sildenafil treatment after BCNR activates genes related to SM preservation and down regulates genes related to fibrosis in the corpora cavernosa. These results provide a mechanistic justification for the use of sildenafil and other PDE5 inhibitors as protective therapy

  18. Optic nerve atrophy

    MedlinePlus

    Optic nerve atrophy is damage to the optic nerve. The optic nerve carries images of what the eye sees to ... problem most often affects older adults. The optic nerve can also be damaged by shock, toxins, radiation, ...

  19. Nerve biopsy (image)

    MedlinePlus

    Nerve biopsy is the removal of a small piece of nerve for examination. Through a small incision, a sample ... is removed and examined under a microscope. Nerve biopsy may be performed to identify nerve degeneration, identify ...

  20. Peripheral Nerve Disorders

    MedlinePlus

    ... spinal cord. Like static on a telephone line, peripheral nerve disorders distort or interrupt the messages between the brain ... body. There are more than 100 kinds of peripheral nerve disorders. They can affect one nerve or many nerves. ...

  1. Evaluation of the brain-derived neurotrophic factor, nerve growth factor and memory in adult rats survivors of the neonatal meningitis by Streptococcus agalactiae.

    PubMed

    Barichello, Tatiana; Lemos, Joelson C; Generoso, Jaqueline S; Carradore, Mirelle M; Moreira, Ana Paula; Collodel, Allan; Zanatta, Jessiele R; Valvassori, Samira S; Quevedo, João

    2013-03-01

    Streptococcus agalactiae (GBS) is a major cause of severe morbidity and mortality in neonates and young infants, causing sepsis, pneumonia and meningitis. The survivors from this meningitis can suffer serious long-term neurological consequences, such as, seizures, hearing loss, learning and memory impairments. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) control the neuronal cell death during the brain development and play an important role in neuronal differentiation, survival and growth of neurons. Neonate Wistar rats, received either 10μL of sterile saline as a placebo or an equivalent volume of GBS suspension at a concentration of 1×10(6)cfu/mL. Sixty days after induction of meningitis, the animals underwent behavioral tests, after were killed and the hippocampus and cortex were retired for analyze of the BDNF and NGF levels. In the open-field demonstrated no difference in motor, exploratory activity and habituation memory between the groups. The step-down inhibitory avoidance, when we evaluated the long-term memory at 24h after training session, we found that the meningitis group had a decrease in aversive memory when compared with the long-term memory test of the sham group. BDNF levels decreased in hippocampus and cortex; however the NGF levels decreased only in hippocampus. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to GBS meningitis. PMID:22683802

  2. Malignant Peripheral Nerve Sheath Tumor Invasion Requires Aberrantly Expressed Epidermal Growth Factor (EGF) Receptors and is Variably Enhanced by Multiple EGF Family Ligands

    PubMed Central

    Byer, Stephanie J.; Brossier, Nicole M.; Peavler, Lafe T.; Eckert, Jenell M.; Watkins, Stacey; Roth, Kevin A.; Carroll, Steven L.

    2013-01-01

    Aberrant epidermal growth factor receptor (EGFR) expression promotes the pathogenesis of malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with neurofibromatosis type 1, but the mechanisms by which EGFR expression promotes MPNST pathogenesis are poorly understood. We hypothesized that inappropriately expressed EGFRs promote MPNST invasion and found that these kinases are concentrated in MPNST invadopodia in vitro. EGFR knockdown inhibited the migration of unstimulated MPNST cells in vitro and exogenous EGF further enhanced MPNST migration in a substrate-specific manner, promoting migration on laminin and, to a lesser extent, collagen. Thus, in this setting, EGF acts as a chemotactic factor. We also found that the 7 known EGFR ligands (EGF, betacellulin, epiregulin, heparin-binding EGF, transforming growth factor α [TGFα], amphiregulin, and epigen) variably enhanced MPNST migration in a concentration-dependent manner, with TGFα being particularly potent. With the exception of epigen, these factors similarly promoted the migration of non-neoplastic Schwann cells. Although transcripts encoding all 7 EGFR ligands were detected in human MPNST cells and tumor tissues, only TGFα was consistently overexpressed and was found to colocalize with EGFR in situ. These data indicate that constitutive EGFR activation, potentially driven by autocrine or paracrine TGFα signaling, promotes the aggressive invasive behavior characteristic of MPNSTs. PMID:23399900

  3. Thermally drawn fibers as nerve guidance scaffolds.

    PubMed

    Koppes, Ryan A; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Abdolrahim Poorheravi, Negin; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

    2016-03-01

    Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth. PMID:26717246

  4. Importance of interaction between nerve growth factor and α9β1 integrin in glial tumor angiogenesis

    PubMed Central

    Walsh, Erin M.; Kim, Richard; Del Valle, Luis; Weaver, Michael; Sheffield, Joel; Lazarovici, Philip; Marcinkiewicz, Cezary

    2012-01-01

    NGF is a growth factor for which the role in the promotion of angiogenesis is still not completely understood. We found that NGF promotes the pathological neovascularization process in glioma through a direct interaction with α9β1 integrin, which is up-regulated on microvascular endothelial cells in cancer tissue. We propagated gHMVEC primary cells using a new method of immune-selection, and these cells demonstrated α9β1 integrin-dependent binding of NGF in a cell adhesion assay. Moreover, NGF induced gHMVEC proliferation and chemotaxis inhibited by specific blockers of α9β1 integrin, such as MLD-disintegrins and monoclonal antibody Y9A2. A Matrigel tube formation assay revealed that NGF significantly increased capillary-like growth from gHMVEC to a level comparable to treatment with VEGF. The snake venom disintegrin, VLO5, inhibited the agonistic effect of both growth factors, whereas the effect of Y9A2 was not statistically significant. Angiogenesis exogenously induced by NGF  was also α9β1-integrin dependent in an embryonic quail CAM system. However, angiogenesis pathologically induced by developing glioma in this system was only sensitive for inhibition with MLD-disintegrin, suggesting a more complex effect of cancer cells on the neovascularization process. The anti-angiogenic effect of MLD-disintegrins is probably related to their pro-apoptotic ability induced in activated tumoral endothelial cells. Therefore, the molecular basis of these disintegrins may be useful for developing new angiostatic pharmaceuticals for application in cancer therapy. PMID:22611032

  5. Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats.

    PubMed

    Wisniewski, Miriam S W; Carvalho-Silva, Milena; Gomes, Lara M; Zapelini, Hugo G; Schuck, Patrícia F; Ferreira, Gustavo C; Scaini, Giselli; Streck, Emilio L

    2016-04-01

    Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-chain α-ketoacids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. However, the effect of accumulating α-ketoacids in MSUD on neurotrophic factors has not been investigated. Thus, the objective of the present study was to evaluate the effects of acute intracerebroventricular administration of α-ketoisocaproic acid (KIC) on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brains of young male rats. Ours results showed that intracerebroventricular administration of KIC decreased BDNF levels in hippocampus, striatum and cerebral cortex, without induce a detectable change in pro-BDNF levels. Moreover, NGF levels in the hippocampus were reduced after intracerebroventricular administration of KIC. In conclusion, these data suggest that the effects of KIC on demyelination and memory processes may be mediated by reduced trophic support of BDNF and NGF. Moreover, lower levels of BDNF and NGF are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying the psychopathology of MSUD, supporting the hypothesis of a neurodegenerative process in MSUD. PMID:26586008

  6. Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling To Enhance Neurite Outgrowth in Developing Neurons

    PubMed Central

    Cohen, Matthew R.; Johnson, William M.; Pilat, Jennifer M.; Kiselar, Janna; DeFrancesco-Lisowitz, Alicia; Zigmond, Richard E.

    2015-01-01

    Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca2+-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca2+-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca2+ signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca2+ signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function. PMID:26416880

  7. Functional Ser205Leu polymorphism of the nerve growth factor receptor (NGFR) gene is associated with vagal autonomic dysregulation in humans

    PubMed Central

    Chang, Chuan-Chia; Fang, Wen-Hui; Chang, Hsin-An; Huang, San-Yuan

    2015-01-01

    Evidence indicates that reduced cardiac vagal (parasympathetic) tone, a robust cardiovascular risk factor, is a trait vulnerability marker of major depressive disorder (MDD). The Ser205/Ser205 genotype of the functional polymorphism (Ser205Leu) of the nerve growth factor receptor (NGFR), also called p75 neurotrophin receptor (p75NTR), gene is reported to increase the risk of MDD. Here, we hypothesized that the NGFR Ser205Leu polymorphism may have an effect on vagal control. A sample of 810 healthy, drug-free, unrelated Han Chinese (413 males, 397 females; mean age 35.17 ± 8.53 years) was included in the NGFR genotyping. Short-term heart rate variability (HRV) was used to assess vagus-mediated autonomic function. Potential HRV covariates, such as mood/anxiety status and serum metabolic parameters, were assessed. Homozygotes of the Ser205 allele had significantly lower high frequency power and root mean square of successive heartbeat interval differences, both HRV indices of vagal modulation, compared to Leu205 allele carriers. Even after adjusting for relevant confounders, these associations remained significant. Further stratification by sex revealed that the associations were observed only in males. Our results implicate that decreased parasympathetic activity is associated with the NGFR Ser205/Ser205 genotype in a gender-specific manner, suggesting a potential role of NGFR polymorphism in modulating cardiac autonomic function. PMID:26278479

  8. Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice

    PubMed Central

    Capsoni, Simona; Marinelli, Sara; Ceci, Marcello; Vignone, Domenico; Amato, Gianluca; Malerba, Francesca; Paoletti, Francesca; Meli, Giovanni; Viegi, Alessandro; Pavone, Flaminia; Cattaneo, Antonino

    2012-01-01

    Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that “painless” hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of “painless” hNGF variants as a new generation of therapeutics for neurodegenerative diseases. PMID:22666365

  9. Neonatal (+)-methamphetamine increases brain derived neurotrophic factor, but not nerve growth factor, during treatment and results in long-term spatial learning deficits.

    PubMed

    Skelton, Matthew R; Williams, Michael T; Schaefer, Tori L; Vorhees, Charles V

    2007-07-01

    In this study, brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were examined at five time points [postnatal day (P)11, 15, 20, 21, and 68 (the latter with or without behavioral testing)] during and after P11-20 (+)-methamphetamine (MA) (10 mg/kg 4 x day) treatment. BDNF in MA-treated animals was elevated on P15 and P20 in the hippocampus but not in the hypothalamus and was unchanged on P11 and P21. On P68 (1 h after Morris water maze testing) MA-treated offspring showed a trend toward higher levels of BDNF in the hippocampus than saline-treated animals. MA treatment increased NGF levels in the hippocampus but only on P20. No effect of MA treatment was observed in the elevated zero maze. MA-treated offspring had increased latencies, cumulative distances, path lengths, and first bearings in the Morris water maze. The findings indicate that early MA exposure induces hippocampal BDNF increases that precede the later emergence of spatial learning deficits. PMID:17606327

  10. Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis.

    PubMed

    Aloe, L; Manni, L; Properzi, F; De Santis, S; Fiore, M

    2000-12-28

    In this study we investigate the neurotoxic action of Cisplatin (6 micrograms/g body weight for 5 treatment cycles during 15 weeks with a total dose of 30 micrograms/g), an antitumor drug, and its effect on the level of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in peripheral tissues. We found that Cisplatin in adult rodents impairs peripheral sensory function and both sympathetic and sensory peripheral innervation as shown by the hot-plate response, catecholamine distribution and substance P immunoreactivity respectively. These changes are associated with decreased NGF in intestine, paws, and bladder while NGF increased in the spinal cord. Also BDNF decreased in bladder and paws and increased in spinal cord and intestine. To further investigate the role of NGF in the pathogenesis of Cisplatin-induced peripheral neuropathies a group of animals was injected with NGF (1 microgram/g every 4 days for 4 times) following Cisplatin treatment and evaluated for sensory function, sympathetic and sensory innervation and BDNF levels. Data demonstrated that exogenous NGF administration is able to restore biochemical, structural and functional changes induced by Cisplatin. These findings suggest that the reduction of NGF availability could be a cause of Cisplatin-induced peripheral neuropathies and that NGF exogenous administration could prevent or reduce Cisplatin neurotoxicity also in cancer patients, reducing the side effects of chemotherapy. PMID:11269929

  11. Protein 4.1N binding to nuclear mitotic apparatus protein in PC12 cells mediates the antiproliferative actions of nerve growth factor.

    PubMed

    Ye, K; Compton, D A; Lai, M M; Walensky, L D; Snyder, S H

    1999-12-15

    Protein 4.1N is a neuronal selective isoform of the erythrocyte membrane cytoskeleton protein 4.1R. In the present study, we demonstrate an interaction between 4.1N and nuclear mitotic apparatus protein (NuMA), a nuclear protein required for mitosis. The binding involves the C-terminal domain of 4.1N. In PC12 cells treatment with nerve growth factor (NGF) elicits translocation of 4. 1N to the nucleus and promotes its association with NuMA. Specific targeting of 4.1N to the nucleus arrests PC12 cells at the G1 phase and produces an aberrant nuclear morphology. Inhibition of 4.1N nuclear translocation prevents the NGF-mediated arrest of cell division, which can be reversed by overexpression of 4.1N. Thus, nuclear 4.1N appears to mediate the antiproliferative actions of NGF by antagonizing the role of NuMA in mitosis. PMID:10594058

  12. Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner

    PubMed Central

    Mnich, K; Carleton, L A; Kavanagh, E T; Doyle, K M; Samali, A; Gorman, A M

    2014-01-01

    Nerve growth factor (NGF) is well characterised as an important pro-survival factor in neuronal cells that can inhibit apoptotic cell death upstream of mitochondrial outer membrane permeabilisation. Here we addressed the question of whether NGF can also protect against apoptosis downstream of caspase activation. NGF treatment promoted a rapid reduction in the level of the p17 subunit of active caspase-3 in PC12 cells that had been induced to undergo apoptosis by various cytotoxins. The mechanism involved TrkA-dependent activation of extracellular signal-regulated kinase (ERK1/2) but not phosphatidylinositol 3-kinase (PI3K)/Akt, and de novo protein synthesis. Involvement of inhibitor of apoptosis proteins (IAPs) and proteasomal degradation were ruled out. In contrast, inhibition of lysosome function using chloroquine and concanamycin A reversed NGF-induced removal of p17. Moreover, in NGF-treated cells, active caspases were found to be localised to lysosomes. The involvement of macroautophagy and chaperone-mediated autophagy were ruled out. Taken together, these findings suggest an anti-apoptotic mechanism by which NGF induces removal of active caspase-3 in a lysosome-dependent manner. PMID:24787014

  13. Seasonal changes in expression of nerve growth factor and its receptors TrkA and p75 in the ovary of wild ground squirrel (Citellus dauricus Brandt)

    PubMed Central

    2014-01-01

    The aim of this study was to investigate the presence of nerve growth factor (NGF) and its receptors tyrosine kinase A (TrkA) and p75 in the ovaries of the wild ground squirrels during the breeding and nonbreeding seasons. In the breeding period, NGF, TrkA and p75 were immunolocalized in granulosa cells, thecal cells, interstitial cells and luteal cells whereas in the nonbreeding period, both of them were detected only in granulosa cells, thecal cells and interstitial cells. Stronger immunostaining of NGF, TrkA and p75 were observed in granulosa cells, thecal cells and interstitial cells in the breeding season compared to the nonbreeding season. Corresponding for the immunohistochemical results, immunoreactivities of NGF and its two receptors were greater in the ovaries of the breeding season then decreased to a relatively low level in the nonbreeding season. The mean mRNA levels of NGF, TrkA and p75 were significantly higher in the breeding season than in the nonbreeding season. In addition, plasma gonadotropins, estradiol-17β and progesterone concentrations were significantly higher in the breeding season than in the nonbreeding season, suggesting that the expression patterns of NGF, and TrkA and p75 were correlated with changes in plasma gonadotropins, estradiol-17β and progesterone concentrations. These results indicated that NGF and its receptors, TrkA and p75 may be involved in the regulation of seasonal changes in the ovarian functions of the wild ground squirrel. PMID:24405743

  14. Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum

    PubMed Central

    Tian, Xinhui; Yue, Rongcai; Zeng, Huawu; Li, Honglin; Shan, Lei; He, Weiwei; Shen, Yunheng; Zhang, Weidong

    2015-01-01

    Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)−1 and (−)−1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)−1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (−)−1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor, and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)−1 and (−)−1. PMID:26585042

  15. Rescuing apoptotic neurons in Alzheimer’s disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin

    PubMed Central

    Kuo, Yung-Chih; Lin, Ching-Chun

    2015-01-01

    Liposomes with cardiolipin (CL) and wheat germ agglutinin (WGA) were developed to permeate the blood–brain barrier and treat Alzheimer’s disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes) were used to transport nerve growth factor (NGF) and curcumin (CUR) across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by β-amyloid1–42 (Aβ1–42) fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ1–42, but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood–brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood–brain barrier and inhibiting neurotoxicity. PMID:25878499

  16. Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling To Enhance Neurite Outgrowth in Developing Neurons.

    PubMed

    Cohen, Matthew R; Johnson, William M; Pilat, Jennifer M; Kiselar, Janna; DeFrancesco-Lisowitz, Alicia; Zigmond, Richard E; Moiseenkova-Bell, Vera Y

    2015-12-01

    Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca(2+)-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca(2+)-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca(2+) signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca(2+) signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function. PMID:26416880

  17. Effects of Comb Tooth Cap Medicinal Mushroom, Hericium ramosum (Higher Basidiomycetes) Mycelia on DPPH Radical Scavenging Activity and Nerve Growth Factor Synthesis.

    PubMed

    Suruga, Kohei; Kadokura, Kazunari; Sekino, Yoshihiro; Nakano, Takafumi; Matsuo, Koichi; Irie, Keiichi; Mishima, Kenichi; Yoneyama, Makoto; Komatsu, Yasuhiro

    2015-01-01

    The goal of this study was to evaluate the antioxidant effects of and nerve growth factor (NGF) synthesis caused by Hericium ramosum mycelia. Wild mushroom fruiting bodies were collected from nature to isolate their mycelia. Pieces of H. ramosum fruiting bodies were plated onto 90-mm Petri dishes with potato dextrose agar medium to isolate their mycelia. Antioxidant activity was measured using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activity in vitro; the ethanol extract from H. ramosum mycelia (63.11 µmol Trolox/g) was more potent than that of other mushroom mycelia extracts. There was a proportional relationship (R2 = 0.7929) between DPPH radical scavenging activity and total phenolic content in extracts of different mushroom mycelia. We investigated the ability of H. ramosum mycelia to inducing NGF synthesis in vivo. Oral administration of H. ramosum mycelia significantly increased concentrations of NGF in the hippocampus of intact mice. These results are the first concerning antioxidant activity and NGF synthesis of H. ramosum mycelia. These mushroom mycelia could be useful as food and/or nutritional supplements because of certain biological functions. PMID:25954959

  18. Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum

    NASA Astrophysics Data System (ADS)

    Tian, Xinhui; Yue, Rongcai; Zeng, Huawu; Li, Honglin; Shan, Lei; He, Weiwei; Shen, Yunheng; Zhang, Weidong

    2015-11-01

    Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)-1 and (-)-1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)-1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (-)-1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor, and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)-1 and (-)-1.

  19. Seasonal changes in expression of nerve growth factor and its receptors TrkA and p75 in the ovary of wild ground squirrel (Citellus dauricus Brandt).

    PubMed

    Li, Ben; Sheng, Xia; Bao, Lihong; Huang, Shiyang; Li, Qinglin; Liu, Yuning; Han, Yingying; Watanabe, Gen; Taya, Kazuyoshi; Weng, Qiang

    2014-01-01

    The aim of this study was to investigate the presence of nerve growth factor (NGF) and its receptors tyrosine kinase A (TrkA) and p75 in the ovaries of the wild ground squirrels during the breeding and nonbreeding seasons. In the breeding period, NGF, TrkA and p75 were immunolocalized in granulosa cells, thecal cells, interstitial cells and luteal cells whereas in the nonbreeding period, both of them were detected only in granulosa cells, thecal cells and interstitial cells. Stronger immunostaining of NGF, TrkA and p75 were observed in granulosa cells, thecal cells and interstitial cells in the breeding season compared to the nonbreeding season. Corresponding for the immunohistochemical results, immunoreactivities of NGF and its two receptors were greater in the ovaries of the breeding season then decreased to a relatively low level in the nonbreeding season. The mean mRNA levels of NGF, TrkA and p75 were significantly higher in the breeding season than in the nonbreeding season. In addition, plasma gonadotropins, estradiol-17β and progesterone concentrations were significantly higher in the breeding season than in the nonbreeding season, suggesting that the expression patterns of NGF, and TrkA and p75 were correlated with changes in plasma gonadotropins, estradiol-17β and progesterone concentrations. These results indicated that NGF and its receptors, TrkA and p75 may be involved in the regulation of seasonal changes in the ovarian functions of the wild ground squirrel. PMID:24405743

  20. Nerve Growth Factor Increases mRNA Levels for the Prion Protein and the β -amyloid Protein Precursor in Developing Hamster Brain

    NASA Astrophysics Data System (ADS)

    Mobley, William C.; Neve, Rachael L.; Prusiner, Stanley B.; McKinley, Michael P.

    1988-12-01

    Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the β protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the β -protein precursor (β -PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and β -PP mRNAs. The increases in PrP and β -PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and β -PP mRNA levels. Increased PrP and β -PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and β -PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes.

  1. The transcription of the human fructose-bisphosphate aldolase C gene is activated by nerve-growth-factor-induced B factor in human neuroblastoma cells.

    PubMed Central

    Buono, P; Conciliis, L D; Izzo, P; Salvatore, F

    1997-01-01

    A DNA region located at around -200 bp in the 5' flanking region (region D) of the human brain-type fructose-bisphosphate aldolase (aldolase C) gene has been analysed. We show by transient transfection assay and electrophoretic-mobility-shift assay (EMSA) that the binding of transcriptional activators to region D is much more efficient (80% versus 30%) in human neuroblastoma cells (SKNBE) than in the non-neuronal cell line A1251, which contains low levels of aldolase C mRNA. The sequence of region D, CAAGGTCA, is very similar to the AAAGGTCA motif present in the mouse steroid 21-hydroxylase gene; the latter motif binds nerve-growth-factor-induced B factor (NGFI-B), which is a member of the thyroid/steroid/retinoid nuclear receptor gene family. Competition experiments in EMSA and antibody-directed supershift experiments showed that NGFI-B is involved in the binding to region D of the human aldolase C gene. Furthermore, the regulation of the aldolase C gene (which is the second known target of NGFI-B) expression during development parallels that of NGFI-B. PMID:9173889

  2. Improved restriction landmark cDNA scanning and its application to global analysis of genes regulated by nerve growth factor in PC12 cells.

    PubMed

    Mayumi, K; Yaoi, T; Kawai, J; Kojima, S; Watanabe, S; Suzuki, H

    1998-07-30

    Restriction landmark cDNA scanning (RLCS) is a novel method by which more than 1000 genes can be simultaneously and quantitatively displayed as two-dimensional gel spots. Here we present an adaptation that allows an individual spot to correspond to a unique gene species without redundancy in more than two gel patterns. Using this improved RLCS, we examined global changes on the gene expression of PC12 cells before and after treatment with nerve growth factor. Among a total of 3000 spots, 21 (0.70%) and 91 (3.03%) spots newly appeared and became more intense with treatment. On the other hand, 15 (0.50%) and 44 (1.47%) spots disappeared, becoming less intense with treatment. These observations suggest that approx. 6% of the detected PC12 genes are up-(3.73%) or down-(1.97%) regulated when the cells differentiate to neuronal cells. In comparison with the results obtained using the expressed-sequence-tag approach, previously reported by Lee et al. (Proc. Natl. Acad. Sci. USA 92 (1995) 8303-8307), RLCS should be useful for quantitatively examining the global change of differentially expressed genes of various expression levels. PMID:9714711

  3. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    PubMed

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. PMID:26883566

  4. Excessive Ovarian Production of Nerve Growth Factor Elicits Granulosa Cell Apoptosis by Setting in Motion a Tumor Necrosis Factor alpha/Stathmin$Mediated Death Signaling Pathway

    PubMed Central

    Garcia-Rudaz, Cecilia; Dorfman, Mauricio; Nagalla, Srinivasa; Svechnikov, Konstantin; Söder, Olle; Ojeda, Sergio R.; Dissen, Gregory A.

    2012-01-01

    Excessive nerve growth factor (NGF) production by the ovary, achieved via a transgenic approach, results in arrested antral follicle growth, reduced ovulatory capacity, and a predisposition to cyst formation in response to mildly elevated LH levels. Two salient features in these mutant mice (termed 17NF) are an elevated production of 17-alpha hydroxyprogesterone (17-OHP4), testosterone (T4) and estradiol (E2) in response to gonadotropins, and an increased frequency of granulosa cell (GC) apoptosis. Here we show that the increase in steroidal response is associated with enhanced expression of Cyp17a1, Hsd17b, and Cyp19a1, which encode the enzymes catalyzing the synthesis of 17-OHP4, T4 and E2, respectively. Using a proteomic approach, we identified stathmin (STMN1), as a protein that is overproduced in 17NF ovaries. In its phosphorylated state, STMN1 mediates a cell death signal initiated by tumor necrosis factor alpha (TNF). STMN1 is expressed in GCs and excessive NGF increases its abundance as well as that of its forms phosphorylated at serine (Ser) 16, 25 and 38. TNF synthesis is also increased in 17NF ovaries, and this change is abolished by blocking neurotrophic tyrosine kinase (NTRK) receptors. Inhibiting TNF actions in vivo by administering a soluble TNF receptor prevented the increase in total and phosphorylated STMN1 production, as well as GC apoptosis in NGF-overproducing ovaries. These results indicate that an excess of NGF in the ovary promotes steroidogenesis by enhancing the expression of enzyme genes involved in 17-OHP4, T4 and E2 synthesis, and causes GC apoptosis by activating a TNF/STMN1-mediated cell death pathway. PMID:21646391

  5. A comparative analysis of the structural, functional and biological differences between Mouse and Human Nerve Growth Factor.

    PubMed

    Paoletti, Francesca; Malerba, Francesca; Ercole, Bruno Bruni; Lamba, Doriano; Cattaneo, Antonino

    2015-03-01

    NGF is the prototype member of the neurotrophin family of proteins that promote the survival and growth of selected neurons in the central and peripheral nervous systems. As for all neurotrophins, NGF is translated as a pre-pro-protein. Over the years, NGF and proNGF of either human or mouse origin, given their high degree of homology, have been exploited for numerous applications in biomedical sciences. The mouse NGF has been considered the golden-standard for bioactivity. Indeed, due to evolutionary relatedness to human NGF and to its ready availability and by assuming identical properties to its human counterpart, the mouse NGF, isolated and purified from sub-maxillary glands, has been tested not only in laboratory practice and in preclinical models, but it has also been evaluated in several human clinical trials. Aiming to validate this assumption, widely believed, we performed a comparative study of the biochemical and biophysical properties of the mouse and human counterparts of NGF and proNGF. The mature and the precursor proteins of either species strikingly differ in their biophysical profiles and, when tested for ligand binding to their receptors, in their in vitro biological activities. We provide a structural rationale that accounts for their different functional behaviors. Despite being highly conserved during evolution, NGF and proNGF of mouse and human origins show distinct properties and therefore special care must be taken in performing experiments with cross-species systems in the laboratory practice, in developing immunoassays, in clinical trials and in pharmacological treatments. PMID:25496838

  6. Expression patterns of T-type Cav3.2 channel and insulin-like growth factor-1 receptor in dorsal root ganglion neurons of mice after sciatic nerve axotomy.

    PubMed

    Lin, Si-Fang; Yu, Xiao-Lu; Liu, Xiao-Ya; Wang, Bing; Li, Cheng-Hui; Sun, Yan-Gang; Liu, Xing-Jun

    2016-10-19

    Substantial evidence indicates that T-type Cav3.2 channel and insulin-like growth factor-1 (IGF-1) contribute to pain hypersensitivity within primary sensory nerves. A recent study suggested that activation of IGF-1 receptor (IGF-1R) could increase Cav3.2 channel currents and further contribute to inflammatory pain sensitivity. However, the expression patterns of Cav3.2 and IGF-1R and their colocalization in dorsal root ganglion (DRG) in chronic neuropathic pain condition remain unknown. In this study, we explored expression patterns of Cav3.2, IGF-1R and their colocalization, and whether phenotypic switch occurs in a subpopulation of Cav3.2 or IGF-1R neurons in mouse DRGs after sciatic nerve axotomy with immunofluorescence, real-time reverse transcription-PCR, and western blot assays. We found that expressions of Cav3.2 and IGF-1R, and their colocalization were not increased in DRGs of mice following axotomy. In addition, Cav3.2 or IGF-1R subpopulation neurons did not acquire significant switch in expression phenotype after sciatic nerve axotomy. Our findings argue for an upregulation of Cav3.2 and IGF-1R expression in lumbar DRGs post-sciatic nerve axotomy and provided an insight for understanding the functions of peripheral afferent Cav3.2 channel and IGF-1/IGF-1R signaling in chronic neuropathic pain. PMID:27571431

  7. A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair.

    PubMed

    Wang, Dong; Huang, Xijun; Fu, Guo; Gu, Liqiang; Liu, Xiaolin; Wang, Honggang; Hu, Jun; Yi, Jianhua; Niu, Xiaofeng; Zhu, Qingtang

    2014-05-15

    Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripheral nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration. PMID:25206757

  8. Nerve conduction velocity

    MedlinePlus

    Nerve conduction velocity (NCV) is a test to see how fast electrical signals move through a nerve. ... normal body temperature. Being too cold slows nerve conduction. Tell your doctor if you have a cardiac ...

  9. Femoral nerve damage (image)

    MedlinePlus

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  10. Ulnar nerve damage (image)

    MedlinePlus

    The ulnar nerve originates from the brachial plexus and travels down arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near the surface of the body where ...

  11. Diabetes and nerve damage

    MedlinePlus

    ... hot or cold When the nerves that control digestion are affected, you may have trouble digesting food. ... harder to control. Damage to nerves that control digestion almost always occurs in people with severe nerve ...

  12. Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats

    PubMed Central

    Zhan, Heqin; Li, Shengying; Sun, Juan; Liu, Ruili; Yan, Fulin; Niu, Bingxuan; Zhang, Haifang; Wang, Xinyao

    2014-01-01

    Aims: The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R) injury in rats and the mechanisms of action of LGB. Materials and Methods: The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF) and neurotrophin-3 (NT-3) were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry. Statistical analysis: All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant. Results: Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05, P < 0.01). LGB significantly increased NGF and NT-3 mRNA (messenger RNA) and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01). Conclusions: LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia. PMID:24550587

  13. Nerve Growth Factor Mediates a Switch in Intracellular Signaling for PGE2-Induced Sensitization of Sensory Neurons from Protein Kinase A to Epac

    PubMed Central

    Vasko, Michael R.; Habashy Malty, Ramy; Guo, Chunlu; Duarte, Djane B.; Zhang, Yihong; Nicol, Grant D.

    2014-01-01

    We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated sensory neurons are grown in the absence of added NGF, but not in cultures grown with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to increase the number of action potentials (APs) evoked by a ramp of current. Growing sensory neurons in culture in the presence of increasing concentrations of NGF increases the expression of Epac2, but not Epac1. An intradermal injection of complete Freund's adjuvant into the rat hindpaw also increases the expression of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect blocked by intraplantar administration of NGF antibodies. Treating cultures grown in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the expression of Epac1, but not Epac2, and did not block the ability of PGE2 to augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1 and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked CGRP release in sensory neurons and the PGE2-induced increase in the number of APs generated by a ramp of current. In neurons grown with no added NGF, Epac siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate that NGF, through increasing Epac2 expression, alters the signaling cascade that mediates PGE2-induced sensitization of sensory neurons, thus providing a novel mechanism for maintaining PGE2-induced hypersensitivity during inflammation. PMID:25126967

  14. Viral vector-based improvement of optic nerve regeneration: characterization of individual axons' growth patterns and synaptogenesis in a visual target.

    PubMed

    Yungher, B J; Luo, X; Salgueiro, Y; Blackmore, M G; Park, K K

    2015-10-01

    Lack of axon growth ability in the central nervous system poses a major barrier to achieving functional connectivity after injury. Thus, a non-transgenic regenerative approach to reinnervating targets has important implications in clinical and research settings. Previous studies using knockout (KO) mice have demonstrated long-distance axon regeneration. Using an optic nerve injury model, here we evaluate the efficacy of viral, RNA interference (RNAi) and pharmacological approaches that target the phosphatase and tensin homolog (PTEN) and signal transducer and activator of transcription-3 pathways to improve long-distance axon regeneration in wild-type mice. Our data show that adeno-associated virus (AAV) expressing short hairpin RNA (shRNA) against PTEN (shPTEN) enhances retinal ganglion cell axon regeneration after crush injury. However, compared with the previous data in PTEN KO mice, AAV-shRNA results in a lesser degree of regeneration, likely due to incomplete gene silencing inherent to RNAi. In comparison, an extensive enhancement in regeneration is seen when AAV-shPTEN is coupled to AAV encoding ciliary neurotrophic factor (CNTF) and to a cyclic adenosine monophosphate (cAMP) analog, allowing axons to travel long distances and reach their target. We apply whole-tissue imaging that facilitates three-dimensional visualization of single regenerating axons and document heterogeneous terminal patterns in the targets. This shows that some axonal populations generate extensive arbors and make synapses with the target neurons. Collectively, we show a combinatorial viral RNAi and pharmacological strategy that improves long-distance regeneration in wild-type animals and provide single fiber projection data that indicates a degree of preservation of target recognition. PMID:26005861

  15. Reactive Oxygen Species, Ki-Ras, and Mitochondrial Superoxide Dismutase Cooperate in Nerve Growth Factor-induced Differentiation of PC12 Cells*

    PubMed Central

    Cassano, Silvana; Agnese, Savina; D'Amato, Valentina; Papale, Massimo; Garbi, Corrado; Castagnola, Patrizio; Ruocco, Maria Rosaria; Castellano, Immacolata; De Vendittis, Emmanuele; Santillo, Mariarosaria; Amente, Stefano; Porcellini, Antonio; Avvedimento, Enrico Vittorio

    2010-01-01

    Nerve growth factor (NGF) induces terminal differentiation in PC12, a pheochromocytoma-derived cell line. NGF binds a specific receptor on the membrane and triggers the ERK1/2 cascade, which stimulates the transcription of neural genes. We report that NGF significantly affects mitochondrial metabolism by reducing mitochondrial-produced reactive oxygen species and stabilizing the electrochemical gradient. This is accomplished by stimulation of mitochondrial manganese superoxide dismutase (MnSOD) both transcriptionally and post-transcriptionally via Ki-Ras and ERK1/2. Activation of MnSOD is essential for completion of neuronal differentiation because 1) expression of MnSOD induces the transcription of a neuronal specific promoter and neurite outgrowth, 2) silencing of endogenous MnSOD by small interfering RNA significantly reduces transcription induced by NGF, and 3) a Ki-Ras mutant in the polylysine stretch at the COOH terminus, unable to stimulate MnSOD, fails to induce complete differentiation. Overexpression of MnSOD restores differentiation in cells expressing this mutant. ERK1/2 is also downstream of MnSOD, as a SOD mimetic drug stimulates ERK1/2 with the same kinetics of NGF and silencing of MnSOD reduces NGF-induced late ERK1/2. Long term activation of ERK1/2 by NGF requires SOD activation, low levels of hydrogen peroxide, and the integrity of the microtubular cytoskeleton. Confocal immunofluorescence shows that NGF stimulates the formation of a complex containing membrane-bound Ki-Ras, microtubules, and mitochondria. We propose that active NGF receptor induces association of mitochondria with plasma membrane. Local activation of ERK1/2 by Ki-Ras stimulates mitochondrial SOD, which reduces reactive oxygen species and produces H2O2. Low and spatially restricted levels of H2O2 induce and maintain long term ERK1/2 activity and ultimately differentiation of PC12 cells. PMID:20495008

  16. Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat.

    PubMed

    Lin, Yong; Wan, Jie-qing; Gao, Guo-yi; Pan, Yao-hua; Ding, Sheng-hao; Fan, Yi-ling; Wang, Yong; Jiang, Ji-yao

    2015-11-01

    Traumatic brain injury (TBI) treatment is a long-term process and requires repeated medicine administration, which, however, can cause high expense, infection, and hemorrhage to patients. To investigate how a long-term expression of nerve growth factor (Ngf) gene affects the injured hippocampus function post-TBI, in this study, a pseudo lentivirus carrying the β-Ngf fusion gene, with green fluorescence protein (GFP) gene, was constructed to show the gene expression and its ability of protecting cells from oxidative damage in vitro. Then, the pseudo lentivirus-carried β-Ngf fusion gene was directly injected into the injured brain to evaluate its influence on the injured hippocampus function post-TBI in vivo. We found that the expression of the pseudo lentivirus-delivered β-Ngf fusion gene lasted more than four-week after the cell transduction and the encoded β-NGF fusion protein could induce the neuron-like PC12 cell differentiation. Moreover, the hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene sped the injured cognitive function recovery of the rat subjected to TBI. Together, our findings indicate that the long-term expression of the β-Ngf fusion gene, delivered by the pseudo lentivirus, can promote the neurite outgrowth of the neuron-like cells and protect the cells from the oxidative damage in vitro, and that the direct and single dose hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene is able to rescue the hippocampus function after the TBI in the rat. PMID:26285082

  17. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain.

    PubMed Central

    Ernfors, P; Ibáñez, C F; Ebendal, T; Olson, L; Persson, H

    1990-01-01

    We have used a pool of degenerate oligonucleotides representing all possible codons in regions of homology between brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) to prime rat hippocampal cDNAs in the polymerase chain reaction. The amplified DNA included a product with significant similarity to NGF and BDNF, which was used to isolate a 1020-nucleotide-long cDNA from a rat hippocampal library. From the nucleotide sequence, a 282-amino-acid-long protein with approximately 45% amino acid similarity to both pig BDNF and rat NGF was deduced. In the adult brain, the mRNA for this protein was predominantly expressed in hippocampus, where it was confined to a subset of pyramidal and granular neurons. The developmental expression in brain showed a clear peak shortly after birth, 1 and 2 weeks earlier than maximal expression of BDNF and NGF, respectively. It was also expressed in several peripheral tissues with the highest level in kidney. The protein, transiently expressed in COS cells, was tested on chicken embryonic neurons and readily stimulated fiber outgrowth from explanted Remak's ganglion and, to a lesser extent, the nodose ganglion. A weak, but consistent, fiber outgrowth response was also seen in the ciliary ganglion and in paravertebral sympathetic ganglia. Moreover, the protein displaced binding of NGF to its receptor, suggesting that it can interact with the NGF receptor. Thus, this factor, although structurally and functionally related to NGF and BDNF, has unique biological activities and represents a member of a family of neurotrophic factors that may cooperate to support the development and maintenance of the vertebrate nervous system. Images PMID:2164684

  18. ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning.

    PubMed

    Su, Chang; Sun, Fen; Cunningham, Rebecca L; Rybalchenko, Nataliya; Singh, Meharvan

    2014-01-01

    Oxidative stress has long been implicated in the pathogenesis of various neurodegenerative disorders such as Alzheimer's disease and stroke. While high levels of oxidative stress are generally associated with cell death, a slight rise of reactive oxygen species (ROS) levels can be protective by "preconditioning" cells to develop a resistance against subsequent challenges. However, the mechanisms underlying such preconditioning (PC)-induced protection are still poorly understood. Previous studies have supported a role of ERK5 (mitogen-activated protein [MAP] kinase 5) in neuroprotection and ischemic tolerance in the hippocampus. In agreement with these findings, our data suggest that ERK5 mediates both hydrogen peroxide (H2O2)-induced PC as well as nerve growth factor (NGF)-induced neuroprotection. Activation of ERK5 partially rescued pheochromocytoma PC12 cells as well as primary hippocampal neurons from H2O2-caused death, while inhibition of ERK5 abolished NGF or PC-induced protection. These results implicate ERK5 signaling as a common downstream pathway for NGF and PC. Furthermore, both NGF and PC increased the expression of the transcription factor, KLF4, which can initiate an anti-apoptotic response in various cell types. Induction of KLF4 by NGF or PC was blocked by siERK5, suggesting that ERK5 is required in this process. siKLF4 can also attenuate NGF- or PC-induced neuroprotection. Overexpression of active MEK5 or KLF4 in H2O2-stressed cells increased Bcl-2/Bax ratio and the expression of NAIP (neuronal apoptosis inhibitory protein). Taken together, our data suggest that ERK5/KLF4 cascade is a common signaling pathway shared by at least two important mechanisms by which neurons can be protected from cell death. PMID:25015774

  19. Evidence that nerve growth factor dependence of sympathetic neurons for survival in vitro may be determined by levels of cytoplasmic free Ca2+.

    PubMed Central

    Koike, T; Tanaka, S

    1991-01-01

    Developing sympathetic neurons established in the presence of nerve growth factor (NGF) die in vitro after acute withdrawal of NGF. This in vitro model mimics the physiological situation in which neurons die during development or after axotomy when trophic support becomes insufficient. We have previously shown that depolarizing agents including high K+ and cholinergic agonists prevent neuronal death induced by acute deprivation of NGF in vitro. Based on this finding, a Ca2+ set-point hypothesis was proposed for the degree of neuronal dependence on tropic factor in vitro. Here we have examined the validity of this hypothesis by measuring the level of cytoplasmic free Ca2+ ([Ca2+]i) with fura-2 as a probe for monitoring Ca2+. (i) There was a good correlation between cell survival in the absence of NGF and [Ca2+]i levels of young sympathetic neurons (1 week in vitro) chronically exposed to various concentrations of extracellular K+, which shows that 50% survival occurred at approximately 184 nM [Ca2+]i and complete survival, independent of trophic support, occurred at approximately 240 nM [Ca2+]i. (ii) The basal level of [Ca2+]i of sympathetic neurons was relatively low (93.0 +/- 10.5 nM) at days 6-8, then increased with incubation time, and finally reached a plateau level of 241 +/- 7 nM at around week 3, when the neurons became independent of NGF for survival. (iii) Sympathetic neurons maintained in the presence of high or low concentrations of Ca2+ displayed altered trophic dependence. Thus, these findings are consistent with this Ca2+ set-point hypothesis for the degree of NGF dependence of sympathetic neurons for survival in vitro. Images PMID:2023936

  20. Effects of varying doses of β-nerve growth factor on the timing of ovulation, plasma progesterone concentration and corpus luteum size in female alpacas (Vicugna pacos).

    PubMed

    Stuart, C C; Vaughan, J L; Kershaw-Young, C M; Wilkinson, J; Bathgate, R; de Graaf, S P

    2015-11-01

    Ovulation in camelids is induced by the seminal plasma protein ovulation-inducing factor (OIF), recently identified as β-nerve growth factor (β-NGF). The present study measured the total protein concentration in alpaca seminal plasma using a bicinchoninic acid (BCA) protein quantification assay and found it to be 22.2±2.0mgmL(-1). To measure the effects of varying doses of β-NGF on the incidence and timing of ovulation, corpus luteum (CL) size and plasma progesterone concentration, 24 female alpacas were synchronised and treated with either: (1) 1mL 0.9% saline (n=5); (2) 4µg buserelin (n=5); (3) 1mg β-NGF protein (n=5); (4) 0.1mg β-NGF (n=5); or (5) 0.01mg β-NGF (n=4). Females were examined by transrectal ultrasonography at 1-2-h intervals between 20 and 45h after treatment or until ovulation occurred, as well as on Day 8 to observe the size of the CL, at which time blood was collected to measure plasma progesterone concentrations. Ovulation was detected in 0/5, 5/5, 5/5, 3/5 and 0/4 female alpacas treated with saline, buserelin, 1, 0.1 and 0.01mg β-NGF, respectively. Mean ovulation interval (P=0.76), CL diameter (P=0.96) and plasma progesterone concentration (P=0.96) did not differ between treatments. Mean ovulation interval overall was 26.2±1.0h. In conclusion, buserelin and 1mg β-NGF are equally effective at inducing ovulation in female alpacas, but at doses ≤0.1mg, β-NGF is not a reliable method for the induction of ovulation. PMID:24965784

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

    PubMed Central

    Buchkovich, K J; Ziff, E B

    1994-01-01

    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 of cell cycle progression. The decrease in p33cdk2 and p34cdc2 coincides with a decrease in the enzymatic activity of cyclinA-p34cdc2, cyclinB-p34cdc2, cyclinE-p33cdk2, and cyclinA-p33cdk2 kinases. The decline in p33cdk2 and p34cdc2 kinase activity in response to NGF is accelerated in cells that over-express the p140trk NGF receptor, suggesting that the timing of the down- regulation is dependent on the level of p140trk and the strength of the NGF signal. The level of cyclin A, a regulatory subunit of p33cdk2 and p34cdc2, is relatively constant during PC12 differentiation. Nevertheless, the DNA binding activity of the cyclinA-associated transcription factor E2F/DP decreases. Thus, NGF down-regulates the activity of cyclin dependent kinases and cyclin-transcription factor complexes during PC12 differentiation. Images PMID:7865886

  2. Seminal Plasma Induces Ovulation in Llamas in the Absence of a Copulatory Stimulus: Role of Nerve Growth Factor as an Ovulation-Inducing Factor.

    PubMed

    Berland, Marco A; Ulloa-Leal, Cesar; Barría, Miguel; Wright, Hollis; Dissen, Gregory A; Silva, Mauricio E; Ojeda, Sergio R; Ratto, Marcelo H

    2016-08-01

    Llamas are considered to be reflex ovulators. However, semen from these animals is reported to be rich in ovulation-inducing factor(s), one of which has been identified as nerve growth factor (NGF). These findings suggest that ovulation in llamas may be elicited by chemical signals contained in semen instead of being mediated by neural signals. The present study examines this notion. Llamas displaying a preovulatory follicle were assigned to four groups: group 1 received an intrauterine infusion (IUI) of PBS; group 2 received an IUI of seminal plasma; group 3 was mated to a male whose urethra had been surgically diverted (urethrostomized male); and group 4 was mated to an intact male. Ovulation (detected by ultrasonography) occurred only in llamas mated to an intact male or given an IUI of seminal plasma and was preceded by a surge in plasma LH levels initiated within an hour after coitus or IUI. In both ovulatory groups, circulating β-NGF levels increased within 15 minutes after treatment, reaching values that were greater and more sustained in llamas mated with an intact male. These results demonstrate that llamas can be induced to ovulate by seminal plasma in the absence of copulation and that copulation alone cannot elicit ovulation in the absence of seminal plasma. In addition, our results implicate β-NGF as an important mediator of seminal plasma-induced ovulation in llamas because ovulation does not occur if β-NGF levels do not increase in the bloodstream, a change that occurs promptly after copulation with an intact male or IUI of seminal plasma. PMID:27355492

  3. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

    PubMed

    Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N W; Casewell, Nicholas R; Undheim, Eivind A B; Vidal, Nicolas; Ali, Syed A; King, Glenn F; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

    2013-01-01

    Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation. PMID:24312363

  4. Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenalf

    PubMed Central

    Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N. W.; Casewell, Nicholas R.; Undheim, Eivind A. B.; Vidal, Nicolas; Ali, Syed A.; King, Glenn F.; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

    2013-01-01

    Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation. PMID:24312363

  5. The impact of two mild stressors on the nerve growth factor (NGF) immunoreactivity in the amygdala in aged rats compared to adult ones.

    PubMed

    Badowska-Szalewska, Ewa; Ludkiewicz, Beata; Krawczyk, Rafał; Moryś, Janusz

    2016-04-01

    Nerve growth factor (NGF) seems to play an important role in the ageing limbic system in response to stress. This study aimed to explore the influence of acute and chronic exposure to high-light open field (HL-OF) or forced swim (FS) stressors on the density of NGF immunoreactive (ir) neurons in the amygdala central (CeA), medial (MeA), lateral (LA) and basolateral (BLA) nuclei in adult (postnatal day 90; P90) and aged (P720) rats. In comparison with non-stressed rats, neither acute nor chronic HL-OF produced significant changes in the density of NGF-ir neurons of studied nuclei in P90 and P720 rats. However, not acute but chronic FS was the factor inducing an increase in the density of NGF-ir neurons in the CeA of both age groups and in the LA of P720 rats. Despite the lack of change in the density of NGF-ir neurons between P90 and P720 non-stressed rats, there were significant age-related changes in NGF-ir cells in FS and/or HL-OF stressed rats in all the tested nuclei, with the exception of the LA. It may be concluded that as far as the influence on NGF-ir cells in amygdaloid nuclei is concerned, HL-OF did not constitute an aggravating factor for rats in the ontogenetic periods studied. Moreover, upregulation of NGF-ir neurons predominantly in CeA after chronic FS seems to be neuroprotective. Age-dependent changes in the density of NGF-ir neurons in stressed rats are probably caused by ageing processes and they may point to dysregulation of excitatory control exerted by the amygdala. PMID:26724365

  6. The exocytotic signaling pathway induced by nerve growth factor in the presence of lyso-phosphatidylserine in rat peritoneal mast cells involves a type D phospholipase.

    PubMed

    Seebeck, J; Westenberger, K; Elgeti, T; Ziegler, A; Schütze, S

    2001-12-15

    Nerve growth factor (NGF) has been previously shown to induce exocytosis in rat peritoneal mast cells (RPMCs) in the presence of lyso-phosphatidylserine (lysoPS) by interacting with high-affinity NGF receptors of the TrkA-type. In RPMCs, type D phosphatidylcholine-selective phospholipases (PLDs) have been postulated to be involved in some exocytotic signaling pathways induced by different agonists. The aim of the present study was to assess a putative functional role of PLD for NGF/lysoPS-induced exocytosis in RPMCs. In 1-[14C]palmitoyl-2-lyso-3-phosphatidylcholine-labelled RPMCs, NGF/lysoPS stimulated the formation of diacylglycerol (DAG) and, in the presence of ethanol (1% [v/v]), phosphatidylethanol (PEtOH). These data indicate PLD-activation by NGF/lysoPS in RPMCs. Preincubation of RPMCs for 2 min with ethanol, an inhibitor of PLD-derived DAG-formation, dose-dependently (IC(50): 0.6% [v/v]) and agonist-selectively inhibited the NGF/lysoPS induced release of [3H]serotonin ([3H]5-HT) in [3H]5-HT-loaded RPMCs, confirming the functional importance of PLD-action. Exocytosis and PEtOH-production was potently inhibited by the broad-spectrum serine/threonine kinase inhibitor staurosporine and activated by the protein kinase C(PKC)-activator PMA (phorbol-12-myristate-13-acetate) suggesting a role for PKC as mediator for NGF/lysoPS-induced activation of PLD. PMID:11730981

  7. Repeated, Intermittent Exposures to diisopropylfluorophosphate in Rats: Protracted Effects on Cholinergic Markers, Nerve Growth Factor-Related Proteins, and Cognitive Function

    PubMed Central

    Terry, Alvin V.; Buccafusco, Jerry J.; Gearhart, Debra A.; Beck, Wayne D.; Middlemore-Risher, Mary-Louise; Truan, Jacob N.; Schwarz, Gary M.; Xu, Meng; Bartlett, Michael G.; Kutiyanawala, Ammar; Pillai, Anilkumar

    2011-01-01

    Organophosphates (OPs) pose a constant threat to human health due to their widespread use as pesticides and their potential employment in military and terrorist attacks. The acute toxicity of OPs has been extensively studied; however, the consequences of prolonged or repeated exposure to levels of OPs that produce no overt signs of acute toxicity (i.e., subthreshold levels) are poorly understood. Further, there is clinical evidence that such repeated exposures to OPs lead to prolonged deficits in cognition, although the mechanism for this effect is unknown. In this study, the behavioral and neurochemical effects of repeated, intermittent, and subthreshold exposures to the alkyl OP, diisopropylfluorophosphate (DFP) were investigated. Rats were injected with DFP subcutaneously (dose range, 0.25-1.0 mg/kg) every other day over the course of 30 days, and then given a two week, DFP-free washout period. In behavioral experiments conducted at various times during the washout period, dose dependent decrements in a water maze hidden platform task and a spontaneous novel object recognition (NOR) procedure were observed, while prepulse inhibition of the acoustic startle response was unaffected. There were modest decreases in open field locomotor activity and grip strength (particularly during the DFP exposure period); however, rotarod performance and water maze swim speeds were not affected. After washout, DFP concentrations were minimal in plasma and brain, however, cholinesterase inhibition was still detectable in the brain. Moreover, the 1.0 mg/kg dose of DFP was associated with (brain region-dependent) alterations in nerve growth factor-related proteins and cholinergic markers. The results of this prospective animal study thus provide evidence to support two novel hypotheses: 1) that intermittent, subthreshold exposures to alkyl OPs can lead to protracted deficits in specific domains of cognition and 2) that such cognitive deficits may be related to persistent functional

  8. Redox regulation of cAMP-responsive element-binding protein and induction of manganous superoxide dismutase in nerve growth factor-dependent cell survival.

    PubMed

    Bedogni, Barbara; Pani, Giovambattista; Colavitti, Renata; Riccio, Antonella; Borrello, Silvia; Murphy, Mike; Smith, Robin; Eboli, Maria Luisa; Galeotti, Tommaso

    2003-05-01

    Reactive oxygen species (ROS) act as both signaling molecules and mediators of cell damage in the nervous system and are implicated in the pathogenesis of neurodegenerative diseases. Neurotrophic factors such as the nerve-derived growth factor (NGF) support neuronal survival during development and promote regeneration after neuronal injury through the activation of intracellular signals whose molecular effectors and downstream targets are still largely unknown. Here we present evidence that early oxidative signals initiated by NGF in PC12 cells, an NGF-responsive cell line, play a critical role in preventing apoptosis induced by serum deprivation. This redox-signaling cascade involves phosphatidylinositol 3-kinase, the small GTPase Rac-1, and the transcription factor cAMP-responsive element-binding protein (CREB), a molecule essential to promote NGF-dependent survival. We found that ROS are necessary for NGF-dependent phosphorylation of CREB, an event directly correlated with CREB activity, whereas hydrogen peroxide induces a robust CREB phosphorylation. Cells exposed to NGF show a late decrease in the intracellular content of ROS when compared with untreated cells and increased expression of the mitochondrial antioxidant enzyme manganese superoxide dismutase, a general inhibitor of cell death. Accordingly, serum deprivation-induced apoptosis was selectively inhibited by low concentrations of the mitochondrially targeted antioxidant Mito Q (mitoquinol/mitoquinone). Taken together, these data demonstrate that the oxidant-dependent activation of CREB is a component of NGF survival signaling in PC12 cells and outline an intriguing circuitry by which a cytosolic redox cascade promotes cell survival at least in part by increasing mitochondrial resistance to oxidative stress. PMID:12609977

  9. Use new PLGL-RGD-NGF nerve conduits for promoting peripheral nerve regeneration

    PubMed Central

    2012-01-01

    Background Nerve conduits provide a promising strategy for peripheral nerve injury repair. However, the efficiency of nerve conduits to enhance nerve regeneration and functional recovery is often inferior to that of autografts. Nerve conduits require additional factors such as cell adhesion molecules and neurotrophic factors to provide a more conducive microenvironment for nerve regeneration. Methods In the present study, poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (PLGL) was modified by grafting Gly-Arg-Gly-Asp-Gly (RGD peptide) and nerve growth factor (NGF) for fabricating new PLGL-RGD-NGF nerve conduits to promote nerve regeneration and functional recovery. PLGL-RGD-NGF nerve conduits were tested in the rat sciatic nerve transection model. Rat sciatic nerves were cut off to form a 10 mm defect and repaired with the nerve conduits. All of the 32 Wistar rats were randomly divided into 4 groups: group PLGL-RGD-NGF, group PLGL-RGD, group PLGL and group autograft. At 3 months after surgery, the regenerated rat sciatic nerve was evaluated by footprint analysis, electrophysiology, and histologic assessment. Experimental data were processed using the statistical software SPSS 10.0. Results The sciatic function index value of groups PLGL-RGD-NGF and autograft was significantly higher than those of groups PLGL-RGD and PLGL. The nerve conduction velocities of groups PLGL-RGD-NGF and autograft were significantly faster than those of groups PLGL-RGD and PLGL. The regenerated nerves of groups PLGL-RGD-NGF and autograft were more mature than those of groups PLGL-RGD and PLGL. There was no significant difference between groups PLGL-RGD-NGF and autograft. Conclusions PLGL-RGD-NGF nerve conduits are more effective in regenerating nerves than both PLGL-RGD nerve conduits and PLGL nerve conduits. The effect is as good as that of an autograft. This work established the platform for further development of the use of PLGL-RGD-NGF nerve conduits for clinical nerve repair

  10. LH release and ovulatory response after intramuscular, intravenous, and intrauterine administration of β-nerve growth factor of seminal plasma origin in female llamas.

    PubMed

    Silva, M; Fernández, A; Ulloa-Leal, C; Adams, G P; Berland, M A; Ratto, M H

    2015-10-15

    The objective of the study was to compare the pituitary and ovarian responses after intramuscular, intravenous, or intrauterine administration of β-nerve growth factor (β-NGF) of seminal plasma origin (SP-NGF) in llamas. In experiment 1, mature female llamas with a growing follicle of 7 mm or greater were assigned randomly to four groups (n = 7/group) and given 2 mg of purified SP-NGF in a volume of 2 mL by (1) intramuscular administration, (2) intravenous administration, and (3) intrauterine infusion, or (4) intrauterine infusion of 2 mL of PBS (negative control). Because ovulations were not detected after intrauterine infusion in experiment 1, a second experiment was done to determine if a higher dose of SP-NGF given by intrauterine infusion, similar to a natural dose during copulation, will elicit an ovulatory response. In experiment 2, llamas with a growing follicle of 7 mm or greater were assigned randomly to three groups (n = 6/per group) given an intrauterine infusion of (1) 4 mL of raw seminal plasma, (2) 4 mL of PBS containing 20 mg of purified llama SP-NGF, or 3) 4 mL of PBS (negative control). In both experiments, the ovaries were examined daily by transrectal ultrasonography using a B-mode scanner and power Doppler mode to detect ovulation and to monitor CL growth, regression, and vascularization. Blood samples were collected to determine plasma LH and progesterone concentrations. In experiment 1, only llamas treated by intramuscular or intravenous administration of SP-NGF ovulated (7 of 7 and 6 of 7, respectively). Plasma LH concentration did not differ between the intramuscular and intravenous SP-NGF-treated groups, nor did CL diameter, CL vascularization, or plasma progesterone concentration profiles. In experiment 2, the ovulation rate was 100% for llamas treated by intrauterine infusion of raw seminal plasma or llama SP-NFG, whereas no ovulations were detected in females treated with PBS. Plasma LH concentrations did not differ between groups

  11. Ethanol induces upregulation of the nerve growth factor receptor CD271 in human melanoma cells via nuclear factor-κB activation

    PubMed Central

    RAPPA, GERMANA; ANZANELLO, FABIO; LORICO, AURELIO

    2015-01-01

    Alcohol consumption is one of the most important, and potentially avoidable, risk factors of human cancer, accounting for 3.6% of all types of cancer worldwide. In a recent meta-analysis, a 20% increased risk of melanoma was linked with regular alcohol consumption. In the present study, the effect of ethanol exposure on the expression of the nerve growth factor receptor, CD271, in human FEMX-I melanoma cells was investigated. Consistent with the derivation of melanocytes from the neural crest, the majority of melanomas express CD271, a protein that is crucial for maintaining the melanoma stem cell properties, including the capacity of self-renewal and resistance to chemotherapy and radiotherapy. Analysis of CD271-sorted subpopulations and clones of FEMX-I cells indicated no hierarchical organization of CD271+ and CD271− cells. In addition, CD271 expression was lost upon growth of FEMX-I melanoma cells in cancer stem cell-like conditions, while it was greatly increased upon CD133 knockdown or exposure to ethanol. After 24-h exposure to 100, 200 and 400 mM ethanol, the percentage of CD271+ cells increased from 14% in control cells to 24, 35 and 88%, respectively. An increase in the percentage of CD271+ cells was already evident 8 h after ethanol exposure and reached a maximum at 48 h. Ethanol-induced upregulation of CD271 was mediated by nuclear factor-κB (NF-κB). In fact, exposure of FEMX-I cells to 100–400 mM ethanol for 24 h resulted in a concentration- and time-dependent increase in NF-κB activity, up to 900% that of control cells. NF-κB activation was due to a decrease in p50 homodimers, which occupy the NF-κB binding site, blocking transactivation. No effects of ethanol on 9 additional signaling pathways of FEMX-I cells were observed. In the presence of CD271 blocking antibodies, NF-κB activation was not prevented, indicating that ethanol did not target CD271 directly. These data demonstrate that ethanol induces expression of CD271 in FEMX-I cells via

  12. Growth-associated protein 43 immunoreactivity in the superficial dorsal horn of the rat spinal cord is localized in atrophic C-fiber, and not in sprouted A-fiber, central terminals after peripheral nerve injury.

    PubMed

    Doubell, T P; Woolf, C J

    1997-09-15

    Peripheral nerve injury induces the up-regulation in dorsal root ganglion cells of growth-associated protein 43 (GAP-43) and its transport to the superficial laminae of the dorsal horn of the spinal cord, where it is located primarily in unmyelinated axons and growth-cone like structures. Peripheral nerve injury also induces the central terminals of axotomized myelinated axons to sprout and form novel synaptic contacts in lamina II of the dorsal horn. To investigate whether the sprouting of A-fiber central terminals into lamina II is the consequence of GAP-43 incorporation into their terminal membranes, we have used an ultrastructural analysis with double labelling to identify the localization of GAP-43 immunoreactivity. Transganglionic transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to identify C-fiber terminals. Transganglionic transport of the B fragment of cholera toxin conjugated to horseradish peroxidase (B-HRP) was used to label A-fiber sciatic nerve central terminals in combination with GAP-43 immunocytochemistry. GAP-43 was found to colocalize only with WGA-HRP- and not with B-HRP-labelled synapses or axons. In addition, many single-labelled GAP-43 synapses were observed. Many of the WGA-HRP-labelled terminals that were characterized by degenerative changes were GAP-43 immunoreactive. Our results indicate that peripheral nerve injury induces novel synapse formation of A fibers in lamina II but that up-regulated levels of GAP-43 are present mainly in other axon projections to the superficial dorsal horn. PMID:9303528

  13. A novel bioactive nerve conduit for the repair of peripheral nerve injury

    PubMed Central

    Li, Bin-bin; Yin, Yi-xia; Yan, Qiong-jiao; Wang, Xin-yu; Li, Shi-pu

    2016-01-01

    The use of a nerve conduit provides an opportunity to regulate cytokines, growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects. We constructed a poly-D-L-lactide (PDLLA)-based nerve conduit that was modified using poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} and β-tricalcium phosphate. The effectiveness of this bioactive PDLLA-based nerve conduit was compared to that of PDLLA-only conduit in the nerve regeneration following a 10-mm sciatic nerve injury in rats. We observed the nerve morphology in the early period of regeneration, 35 days post injury, using hematoxylin-eosin and methylene blue staining. Compared with the PDLLA conduit, the nerve fibers in the PDLLA-based bioactive nerve conduit were thicker and more regular in size. Muscle fibers in the soleus muscle had greater diameters in the PDLLA bioactive group than in the PDLLA only group. The PDLLA-based bioactive nerve conduit is a promising strategy for repair after sciatic nerve injury. PMID:26981105

  14. A silk sericin/silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve.

    PubMed

    Xie, Hongjian; Yang, Wen; Chen, Jianghai; Zhang, Jinxiang; Lu, Xiaochen; Zhao, Xiaobo; Huang, Kun; Li, Huili; Chang, Panpan; Wang, Zheng; Wang, Lin

    2015-10-28

    Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve. PMID:26332703

  15. steve bAccumulation of nerve growth factor and its receptors in the uterus and dorsal root ganglia in a mouse model of adenomyosis

    PubMed Central

    2011-01-01

    Background Adenomyosis is a common gynecological disease, which is accompanied by a series of immunological and neuroendocrinological changes. Nerve growth factor (NGF) plays a critical role in producing pain, neural plasticity, immunocyte aggregation and release of inflammatory factors. This study aimed to investigate the expression of NGF and its two receptors in uteri and dorsal root ganglia (DRG) in an adenomyosis mouse model, as well as their relationship with the severity of adenomyosis. Methods Forty newborn ICR mice were randomly divided into the adenomyosis model group and control group (n = 20 in each group). Mice in the adenomyosis model group were orally dosed with 2.7 μmol/kg tamoxifen on days 2-5 after birth. Experiments were conducted to identify the expression of NGF- beta and its receptors, tyrosine kinase receptor (trkA) and p75 neurotrophin receptor (p75NTR), in the uterus and DRG in four age groups (90+/-5 d, 140+/-5 d, 190+/-5 d and 240+/-5 d; n = 5 mice in each group) by western bolt, immunochemistry and real time reverse transcription-polymerase chain reaction. Results Adenomyosis, which became more serious as age increased, was successfully induced in dosed ICR mice. NGF-beta, trkA and p75NTR protein levels in the uterus and trkA mRNA levels in DRG were higher in the older aged adenomyosis model group than those in controls (190+/-5 d and 240+/-5 d groups, P < 0.05). The expression of NGF-beta and its receptors in the uterus increased gradually as age increased for adenomyosis mice (190+/-5 d and 240+/-5 d, P < 0.05, compared with 90+/-5 d) but it showed little change in control mice. The mRNA level of trkA in DRG also increased as age increased in the adenomyosis model group (190+/-5 d and 240+/-5 d, P < 0.05, compared with 90+/-5 d) but was unchanged in controls. The mRNA level of p75NTR in DRG was not different between the adenomyosis and control groups and was stable from young to old mice. Conclusions NGF- beta can be used as an

  16. Low frequency of plasma nerve-growth factor detection is associated with death of memory B lymphocytes in HIV-1 infection

    PubMed Central

    TITANJI, K; NILSSON, A; MÖRCH, C; SAMUELSSON, A; SÖNNERBORG, A; GRUTZMEIER, S; ZAZZI, M; DE MILITO, A

    2003-01-01

    Nerve growth factor (NGF) regulates B cell activation and differentiation and is an autocrine survival factor for memory B lymphocytes. We have reported recently that the number of memory B cells is reduced during HIV-1 infection. In this study we evaluated whether alteration in the NGF supply was involved in memory B cell loss in HIV-1-infected subjects. High rate of cell death in vitro was observed in memory B cells from HIV-1-infected individuals compared to uninfected donors (26·2 ± 2·5%versus 7·9 ± 1·4%, P < 0·001). The increased expression of Fas on memory B cells from infected subjects did not enhance the susceptibility of the cells to Fas-mediated apoptosis in vitro. The frequency of NGF detection in plasma from HIV-1-infected subjects was significantly lower than in healthy donors (33·6%versus 63·6%, P < 0·001). Also, the median plasma NGF in HIV-1-infected individuals was significantly lower than in uninfected controls (5 versus 14 pg/ml, respectively, P < 0·01). Interestingly, the plasma NGF level was correlated directly 1to the percentage of memory B cells (P < 0·05). HIV-1-infected subjects with a low number of peripheral memory B cells had a reduced incidence of plasmatic NGF (7·4%) compared to patients with a normal level of memory B cells (37%, P < 0·01). Moreover, the addition of recombinant NGF (1 µg/ml) to cultures of purified B cells reduced cell death of memory B cells from HIV-1-infected subjects from 24·04 ± 3·0% to 17·4 ± 1·3% (P < 0·01). HIV-1-infected individuals also carried higher levels of natural anti-NGF autoantibodies compared to uninfected subjects. In conclusion, we found that memory B cells from HIV-1-infected individuals are primed for cell death. Our study suggests an association between low frequency of plasma NGF detection and the increased cell death of memory B lymphocytes observed during HIV-1 infection. Low levels of NGF in plasma may be due to reduced supply or to NGF binding to natural anti

  17. Efficacy, safety, and tolerability of fulranumab, an anti-nerve growth factor antibody, in the treatment of patients with moderate to severe osteoarthritis pain.

    PubMed

    Sanga, Panna; Katz, Nathaniel; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Haeussler, Juergen; Thipphawong, John

    2013-10-01

    Nerve growth factor (NGF) is increased in chronic pain conditions. This study examined analgesic efficacy and safety of fulranumab, a fully human monoclonal anti-NGF antibody, in adults with chronic osteoarthritis pain. Patients (n=466, intent-to-treat) were randomized to receive, in addition to their current pain therapy, subcutaneous injections in 1 of 6 parallel treatment groups: placebo (n=78), fulranumab 1 mg (n=77) or 3 mg (n=79) every 4 weeks (Q4wk), 3 mg (n=76), 6 mg (n=78), or 10 mg (n=78) every 8 weeks (Q8wk). Primary efficacy results showed that fulranumab significantly reduced the average pain intensity score (P < or = 0.030) from baseline to week 12 compared with placebo in the 3mgQ4wk, 6mgQ8wk, and 10mgQ8wk groups. Secondary efficacy outcomes indicated that significant improvement occurred compared with placebo at week 12 on the Western Ontario and McMaster Universities Osteoarthritis Index subscales of pain, stiffness, and physical function (P < 0.040) across all fulranumab groups except 1mgQ4wk, on the Brief Pain Inventory-Short Form subscales of pain intensity (P < or = 0.016) and pain interference (P < or = 0.030) in the 3mgQ4wk and 10mgQ8wk groups, and on the Patient Global Assessment score (P < or = 0.040) in the 3mgQ4wk, 6mgQ8wk, and 10mgQ8wk groups. The most common (> or = 5% of patients) treatment-emergent adverse events in overall fulranumab groups during the first 12weeks included paresthesia (7%), headache (5%), and nasopharyngitis (5%). Most neurologic-related treatment-emergent adverse events were mild or moderate and resolved at the end of week 12. Serious adverse events occurred in 3 patients, but they were not neurologically related and resolved before study completion. Fulranumab treatment resulted in statistically significant efficacy in pain measures and physical function versus placebo and was generally well tolerated. PMID:23748114

  18. Bioactivity of ovulation inducing factor (or nerve growth factor) in bovine seminal plasma and its effects on ovarian function in cattle.

    PubMed

    Tribulo, P; Bogle, O; Mapletoft, R J; Adams, G P

    2015-06-01

    To understand the role of ovulation-inducing factor (or nerve growth factor) (OIF [NGF]) in bovine seminal plasma, we (1) used an in vivo llama bioassay to test the hypothesis that bovine seminal plasma induces ovulation and CL development in llamas similar to that of llama seminal plasma when the dose of seminal plasma is adjusted to ovulation-inducing factor content (experiment 1) and (2) determined the effect of bovine seminal plasma on the interval to ovulation and luteal development in heifers (experiment 2). Within species, seminal plasma was pooled (n = 160 bulls, n = 4 llamas), and the volume of seminal plasma used for treatment was adjusted to a total dose of 250 μg of ovulation-inducing factor. In experiment 1, mature female llamas were assigned randomly to four groups and treated intramuscularly with either 10 mL of PBS (negative control, n = 5), 50-μg GnRH (positive control, n = 5), 6-mL of llama seminal plasma (n = 6), or 12 mL of bull seminal plasma (n = 6). Ovulation and CL development were monitored by transrectal ultrasonography. In experiment 2, beef heifers were given a luteolytic dose of prostaglandin followed by 25-mg porcine LH (pLH) 12 hours later to induce ovulation. Heifers were assigned randomly to three groups and given 12 mL bovine seminal plasma intramuscularly 12 hours after pLH treatment (n = 10), within 4 hours after ovulation (n = 9), or no treatment (control, n = 10). Ovulation was monitored by ultrasonography every 4 hours, and the CL development was monitored daily until the next ovulation. In experiment 1, ovulation was detected in 0/5, 4/5, 4/6, 4/6 llamas in the PBS, GnRH, llama seminal plasma, and bovine seminal plasma groups, respectively (P < 0.05). Luteal development was not different among groups. In experiment 2, the interval to ovulation was more synchronous (range: 4 vs. 22 hours; P < 0.0001) in heifers treated with seminal plasma before ovulation compared with the other groups. Luteal development was not different

  19. Controlled Delivery of FK506 to Improve Nerve Regeneration.

    PubMed

    Labroo, Pratima; Ho, Scott; Sant, Himanshu; Shea, Jill; Gale, Bruce K; Agarwal, Jay

    2016-09-01

    Autologous nerve grafts are the current "gold standard" for repair of large nerve gaps. However, they cause morbidity at the donor nerve site, only a limited amount of nerve can be harvested, and there is the potential for mismatches in size and fascicular patterns between the nerve stumps and the graft. Nerve conduits are a promising alternative to autografts and can act as guidance cues for the regenerating axons and allow for tension free bridging, without the need to harvest donor nerve. Separately, FK506, and FDA-approved small molecule, has been shown to enhance axon growth and peripheral nerve regeneration. This article describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA)-based nerve guide conduit for controlled local delivery of FK506. An FK506 dosage curve was acquired to determine the minimum in vitro concentration for optimal axonal outgrowth of dorsal root ganglion (DRG) cells, then PLGA devices were designed and tested in a diffusion chamber, and finally the bioactivity of the released media was evaluated by measuring axon growth in DRG cells exposed to the media for 72 h. The combined drug delivery nerve guide was able to release FK506 for 20 days at concentrations (1-20 ng/mL) that were shown to enhance DRG axon growth. Furthermore, the released FK506 was bioactive and able to enhance DRG axon growth. The combined drug delivery nerve guide can release FK506 for extended periods of time and enhance axon growth, and has the potential to improve nerve regeneration after a peripheral nerve injury. PMID:27058050

  20. Ulnar nerve damage (image)

    MedlinePlus

    ... arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near ... surface of the body where it crosses the elbow, so prolonged pressure on the elbow or entrapment ...

  1. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  2. Radial nerve dysfunction (image)

    MedlinePlus

    The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

  3. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  4. Nerve conduction velocity

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003927.htm Nerve conduction velocity To use the sharing features on this page, please enable JavaScript. Nerve conduction velocity (NCV) is a test to see how ...

  5. Assessing nerves in leprosy.

    PubMed

    Garbino, José Antonio; Heise, Carlos Otto; Marques, Wilson

    2016-01-01

    Leprosy neuropathy is dependent on the patient's immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation. PMID:26773623

  6. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  7. Radial nerve dysfunction

    MedlinePlus

    ... nerve leads to problems with movement in the arm and wrist and with sensation in the back of the arm or hand. ... to the radial nerve, which travels down the arm and controls movement of the triceps muscle at ...

  8. Degenerative Nerve Diseases

    MedlinePlus

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

  9. Mechanisms of cancer dissemination along nerves.

    PubMed

    Amit, Moran; Na'ara, Shorook; Gil, Ziv

    2016-06-01

    The local extension of cancer cells along nerves is a frequent clinical finding for various tumours. Traditionally, nerve invasion was assumed to occur via the path of least resistance; however, recent animal models and human studies have revealed that cancer cells have an innate ability to actively migrate along axons in a mechanism called neural tracking. The tendency of cancer cells to track along nerves is supported by various cell types in the perineural niche that secrete multiple growth factors and chemokines. We propose that the perineural niche should be considered part of the tumour microenvironment, describe the molecular cues that facilitate neural tracking and suggest methods for its inhibition. PMID:27150016

  10. Laryngeal nerve damage

    MedlinePlus

    Laryngeal nerve damage is injury to one or both of the nerves that are attached to the voice box. ... Injury to the laryngeal nerves is uncommon. When it does occur, it can be from: A complication of neck or chest surgery (especially thyroid, lung, ...

  11. High Median Nerve Injuries.

    PubMed

    Isaacs, Jonathan; Ugwu-Oju, Obinna

    2016-08-01

    The median nerve serves a crucial role in extrinsic and intrinsic motor and sensory function to the radial half of the hand. High median nerve injuries, defined as injuries proximal to the anterior interosseous nerve origin, therefore typically result in significant functional loss prompting aggressive surgical management. Even with appropriate recognition and contemporary nerve reconstruction, however, motor and sensory recovery may be inadequate. With isolated persistent high median nerve palsies, a variety of available tendon transfers can improve key motor functions and salvage acceptable use of the hand. PMID:27387077

  12. [Ganglia of peripheral nerves].

    PubMed

    Tatagiba, M; Penkert, G; Samii, M

    1993-01-01

    The authors present two different types of ganglion affecting the peripheral nerves: extraneural and intraneural ganglion. Compression of peripheral nerves by articular ganglions is well known. The surgical management involves the complete removal of the lesion with preservation of most nerve fascicles. Intraneural ganglion is an uncommon lesion which affects the nerve diffusely. The nerve fascicles are usually intimately involved between the cysts, making complete removal of all cysts impossible. There is no agreement about the best surgical management to be applied in these cases. Two possibilities are available: opening of the epineural sheath lengthwise and pressing out the lesion; or resection of the affected part of the nerve and performing a nerve reconstruction. While in case of extraneural ganglion the postoperative clinical evolution is very favourable, only long follow up studies will reveal in case of intraneural ganglion the best surgical approach. PMID:8128785

  13. Assessment of nerve morphology in nerve activation during electrical stimulation

    NASA Astrophysics Data System (ADS)

    Gomez-Tames, Jose; Yu, Wenwei

    2013-10-01

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

  14. 15d-prostaglandin J2 enhancement of nerve growth factor-induced neurite outgrowth is blocked by the chemoattractant receptor- homologous molecule expressed on T-helper type 2 cells (CRTH2) antagonist CAY10471 in PC12 cells.

    PubMed

    Hatanaka, Michiyoshi; Shibata, Norihiro; Shintani, Norihito; Haba, Ryota; Hayata, Atsuko; Hashimoto, Hitoshi; Baba, Akemichi

    2010-01-01

    The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is the most recently identified prostaglandin (PG) receptor for both PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We examined the mechanism by which 15d-PGJ(2) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. CAY10471 (CRTH2 antagonist) inhibited both the neurite-promotion and p38 mitogen-activated protein (MAP) kinase phosphorylation induced by 15d-PGJ(2). In contrast, 13,14-dihydro-15-keto-PGD(2 )(DK-PGD(2)) (selective CRTH2 agonist) stimulated its phosphorylation but failed to produce neurite-promoting effects. These suggest, for the first time, the action of 15d-PGJ(2) is mediated by CRTH2, although the CRTH2 activation alone is insufficient for the underlying action. PMID:20424389

  15. Effects of Wharton's jelly cells of the human umbilical cord on acute spinal cord injury in rats, and expression of interleukin-1β and nerve growth factor in spinal cord tissues.

    PubMed

    Li, Cheng; Chen, Xiao; Qiao, Suchi; Liu, Xinwei; Liu, Chang; Zhu, Degang; Su, Jiacan; Wang, Zhiwei

    2016-08-01

    To study the effects of Wharton's jelly cells (WJCs) on acute spinal cord injury (SCI), 81 rats were divided into a sham surgery group, a model group, and a WJC transplantation group (n = 27). Motor functions of the model and WJC transplantation groups were partially recovered, and the recovery was better in the latter group. The WJC transplantation group had integral spinal cord tissues. Compared with the model group, the WJC transplantation group expressed significantly less interleukin-1β (IL-1β) and more nerve growth factor (NGF) (P < 0.05). WJC transplantation changed the microenvironment of the SCI site, inhibited IL-1β expression, increased NGF expression, promoted the recovery of neurological function, and relieved secondary SCI. PMID:25801039

  16. Handcrafted multilayer PDMS microchannel scaffolds for peripheral nerve regeneration.

    PubMed

    Hossain, Ridwan; Kim, Bongkyun; Pankratz, Rachel; Ajam, Ali; Park, Sungreol; Biswal, Sibani L; Choi, Yoonsu

    2015-12-01

    Injuries that result in the loss of limb functionality may be caused by the severing of the peripheral nerves within the affected limb. Several bioengineered peripheral nerve scaffolds have been developed in order to provide the physical support and topographical guidance necessary for the naturally disorganized axon outgrowth to reattach to distal nerve stumps as an alternative to other procedures, like nerve grafting. PDMS has been chosen for the base material of the scaffolds due to its biocompatibility, flexibility, transparency, and well-developed fabrication techniques. The process of observing the axon outgrowth across the nerve gaps with PDMS scaffolds has been challenging due to the limited number and fineness of longitudinal sections that can be extracted from harvested nerve tissue samples after implantation. To address this, multilayer microchannel scaffolds were developed with the object of providing more refined longitudinal observation of axon outgrowth by longitudinally 'sectioning' the device during fabrication, removing the need for much of the sample preparation process. This device was then implanted into the sciatic nerves of Lewis rats, and then harvested after two and four weeks to analyze the difference in nerve regeneration between two different time periods. The present layer by layer structure, which is separable after nerve regeneration and is treated as an individual layer during the histology process, provides the details of biological events during axonal regeneration. Confocal microscopic imaging showed the details of peripheral nerve regeneration including nerve branches and growth cones observable from within the microchannels of the multilayer PDMS microchannel scaffolds. PMID:26494637

  17. A Biosynthetic Nerve Guide Conduit Based on Silk/SWNT/Fibronectin Nanocomposite for Peripheral Nerve Regeneration

    PubMed Central

    Mottaghitalab, Fatemeh; Farokhi, Mehdi; Zaminy, Arash; Kokabi, Mehrdad; Soleimani, Masoud; Mirahmadi, Fereshteh

    2013-01-01

    As a contribution to the functionality of nerve guide conduits (NGCs) in nerve tissue engineering, here we report a conduit processing technique through introduction and evaluation of topographical, physical and chemical cues. Porous structure of NGCs based on freeze-dried silk/single walled carbon nanotubes (SF/SWNTs) has shown a uniform chemical and physical structure with suitable electrical conductivity. Moreover, fibronectin (FN) containing nanofibers within the structure of SF/SWNT conduits produced through electrospinning process have shown aligned fashion with appropriate porosity and diameter. Moreover, fibronectin remained its bioactivity and influenced the adhesion and growth of U373 cell lines. The conduits were then implanted to 10 mm left sciatic nerve defects in rats. The histological assessment has shown that nerve regeneration has taken places in proximal region of implanted nerve after 5 weeks following surgery. Furthermore, nerve conduction velocities (NCV) and more myelinated axons were observed in SF/SWNT and SF/SWNT/FN groups after 5 weeks post implantation, indicating a functional recovery for the injured nerves. With immunohistochemistry, the higher S-100 expression of Schwann cells in SF/SWNT/FN conduits in comparison to other groups was confirmed. In conclusion, an oriented conduit of biocompatible SF/SWNT/FN has been fabricated with acceptable structure that is particularly applicable in nerve grafts. PMID:24098649

  18. The Furcal Nerve Revisited

    PubMed Central

    Dabke, Harshad V.

    2014-01-01

    Atypical sciatica and discrepancy between clinical presentation and imaging findings is a dilemma for treating surgeon in management of lumbar disc herniation. It also constitutes ground for failed back surgery and potential litigations thereof. Furcal nerve (Furcal = forked) is an independent nerve with its own ventral and dorsal branches (rootlets) and forms a link nerve that connects lumbar and sacral plexus. Its fibers branch out to be part of femoral and obturator nerves in-addition to the lumbosacral trunk. It is most commonly found at L4 level and is the most common cause of atypical presentation of radiculopathy/sciatica. Very little is published about the furcal nerve and many are unaware of its existence. This article summarizes all the existing evidence about furcal nerve in English literature in an attempt to create awareness and offer insight about this unique entity to fellow colleagues/professionals involved in spine care. PMID:25317309

  19. Sciatic nerve injection injury.

    PubMed

    Jung Kim, Hyun; Hyun Park, Sang

    2014-06-11

    Nerve injury is a common complication following intramuscular injection and the sciatic nerve is the most frequently affected nerve, especially in children, the elderly and underweight patients. The neurological presentation may range from minor transient pain to severe sensory disturbance and motor loss with poor recovery. Management of nerve injection injury includes drug treatment of pain, physiotherapy, use of assistive devices and surgical exploration. Early recognition of nerve injection injury and appropriate management are crucial in order to reduce neurological deficit and to maximize recovery. Sciatic nerve injection injury is a preventable event. Total avoidance of intramuscular injection is recommended if other administration routes can be used. If the injection has to be administered into the gluteal muscle, the ventrogluteal region (gluteal triangle) has a more favourable safety profile than the dorsogluteal region (the upper outer quadrant of the buttock). PMID:24920643

  20. PERIPHERAL NERVE REGENERATION: CELL THERAPY AND NEUROTROPHIC FACTORS

    PubMed Central

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

    2015-01-01

    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. PMID:27027067

  1. Endoscopic Facial Nerve Surgery.

    PubMed

    Marchioni, Daniele; Soloperto, Davide; Rubini, Alessia; Nogueira, João Flávio; Badr-El-Dine, Mohamed; Presutti, Livio

    2016-10-01

    Tympanic facial nerve segment surgery has been traditionally performed using microscopic approaches, but currently, exclusive endoscopic approaches have been performed for traumatic, neoplastic, or inflammatory diseases, specially located at the geniculate ganglion, greater petrosal nerve, and second tract of the facial nerve, until the second genu. The tympanic segment of the facial nerve can be reached and visualized using an exclusive transcanal endoscopic approach, even in poorly accessible regions such as the second genu and geniculate ganglion, avoiding mastoidectomy, bony demolition, and meningeal or cerebral lobe tractions, with low complication rates using a minimally invasive surgical route. PMID:27468633

  2. Engineering a multimodal nerve conduit for repair of injured peripheral nerve.

    PubMed

    Quigley, A F; Bulluss, K J; Kyratzis, I L B; Gilmore, K; Mysore, T; Schirmer, K S U; Kennedy, E L; O'Shea, M; Truong, Y B; Edwards, S L; Peeters, G; Herwig, P; Razal, J M; Campbell, T E; Lowes, K N; Higgins, M J; Moulton, S E; Murphy, M A; Cook, M J; Clark, G M; Wallace, G G; Kapsa, R M I

    2013-02-01

    Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

  3. Engineering a multimodal nerve conduit for repair of injured peripheral nerve

    NASA Astrophysics Data System (ADS)

    Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

    2013-02-01

    Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

  4. Intraoperative vagal nerve monitoring.

    PubMed

    Leonetti, J P; Jellish, W S; Warf, P; Hudson, E

    1996-08-01

    A variety of benign and malignant neoplasms occur in the superior cervical neck, parapharyngeal space or the infratemporal fossa. The surgical resection of these lesions may result in postoperative iatrogenic injury to the vagus nerve with associated dysfunctional swallowing and airway protection. Anatomic and functional preservation of this critical cranial nerve will contribute to a favorable surgical outcome. Fourteen patients with tumors of the cervical neck or adjacent skull base underwent intraoperative vagal nerve monitoring in an attempt to preserve neural integrity following tumor removal. Of the 11 patients with anatomically preserved vagal nerves in this group, seven patients had normal vocal cord mobility following surgery and all 11 patients demonstrated normal vocal cord movement by six months. In an earlier series of 23 patients with tumors in the same region who underwent tumor resection without vagal nerve monitoring, 18 patients had anatomically preserved vagal nerves. Within this group, five patients had normal vocal cord movement at one month and 13 patients demonstrated normal vocal cord movement at six months. This paper will outline a technique for intraoperative vagal nerve monitoring utilizing transcricothyroid membrane placement of bipolar hook-wire electrodes in the vocalis muscle. Our results with the surgical treatment of cervical neck and lateral skull base tumors for patients with unmonitored and monitored vagal nerves will be outlined. PMID:8828272

  5. Inferior alveolar nerve repositioning.

    PubMed

    Louis, P J

    2001-09-01

    Nerve repositioning is a viable alternative for patients with an atrophic edentulous posterior mandible. Patients, however, should be informed of the potential risks of neurosensory disturbance. Documentation of the patient's baseline neurosensory function should be performed with a two-point discrimination test or directional brush stroke test preoperatively and postoperatively. Recovery of nerve function should be expected in 3 to 6 months. The potential for mandibular fracture when combining nerve repositioning with implant placement also should be discussed with the patient. This can be avoided by minimizing the amount of buccal cortical plate removal during localization of the nerve and maintaining the integrity of the inferior cortex of the mandible. Additionally, avoid overseating the implant, thus avoiding stress along the inferior border of the mandible. The procedure does allow for the placement of longer implants, which should improve implant longevity. Patients undergoing this procedure have expressed overall satisfaction with the results. Nerve repositioning also can be used to preserve the inferior alveolar nerve during resection of benign tumors or cysts of the mandible. This procedure allows the surgeon to maintain nerve function in situations in which the nerve would otherwise have to be resected. PMID:11665379

  6. Distal median nerve dysfunction

    MedlinePlus

    ... Names Neuropathy - distal median nerve Images Central nervous system and peripheral nervous system References Jarvik JG, Comstock BA, Kliot M, et al. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomized ... D. Disorders of peripheral nerves. In: Daroff RB, Fenichel GM, Jankovic J, ...

  7. Optic Nerve Decompression

    MedlinePlus

    ... canals). The optic nerve is the “nerve of vision” and extends from the brain, through your skull, and into your eye. A ... limited to, the following: loss of vision, double vision, inadequate ... leakage of brain fluid (CSF), meningitis, nasal bleeding, infection of the ...

  8. Does glioblastoma cyst fluid promote sciatic nerve regeneration?

    PubMed Central

    Özay, Rafet; Aktaş, Abit; Taşkapılıoğlu, Mevlüt Özgür; Gürer, Bora; Erdoğan, Bülent; Çağlar, Yusuf Şükrü

    2015-01-01

    Glioblastoma cyst fluid contains growth factors and extracellular matrix proteins which are known as neurotrophic and neurite-promoting agents. Therefore, we hypothesized that glioblastoma cyst fluid can promote the regeneration of injured peripheral nerves. To validate this hypothesis, we transected rat sciatic nerve, performed epineural anastomosis, and wrapped the injured sciatic nerve with glioblastoma cyst fluid- or saline-soaked gelatin sponges. Neurological function and histomorphological examinations showed that compared with the rats receiving local saline treatment, those receiving local glioblastoma cyst fluid treatment had better sciatic nerve function, fewer scars, greater axon area, counts and diameter as well as fiber diameter. These findings suggest that glioblastoma cyst fluid can promote the regeneration of injured sciatic nerve and has the potential for future clinical application in patients with peripheral nerve injury. PMID:26692863

  9. Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

    PubMed

    Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

    2015-12-01

    During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure. PMID:26420473

  10. Trauma-induced schwannoma of the recurrent laryngeal nerve after thyroidectomy.

    PubMed

    Kennedy, William P; Brody, Robert M; LiVolsi, Virginia A; Wang, Amber R; Mirza, Natasha A

    2016-06-01

    Laryngeal schwannomas are rare, benign tumors, most often arising from the superior laryngeal nerve. We describe a case of a 68-year-old female with a laryngeal schwannoma of the recurrent laryngeal nerve after traumatic injury. We postulate that trauma to the recurrent laryngeal nerve during thyroidectomy or thyroplasty incited growth of a nerve sheath tumor. This is the first reported case of a trauma-induced schwannoma of the recurrent laryngeal nerve and second case of a recurrent laryngeal nerve schwannoma. Although rare, this case demonstrates that these tumors should be considered during workup of vocal cord paresis after surgery or failed thyroplasty. Laryngoscope, 126:1408-1410, 2016. PMID:26421595

  11. Radial Nerve Tendon Transfers.

    PubMed

    Cheah, Andre Eu-Jin; Etcheson, Jennifer; Yao, Jeffrey

    2016-08-01

    Radial nerve palsy typically occurs as a result of trauma or iatrogenic injury and leads to the loss of wrist extension, finger extension, thumb extension, and a reduction in grip strength. In the absence of nerve recovery, reconstruction of motor function involves tendon transfer surgery. The most common donor tendons include the pronator teres, wrist flexors, and finger flexors. The type of tendon transfer is classified based on the donor for the extensor digitorum communis. Good outcomes have been reported for most methods of radial nerve tendon transfers as is typical for positional tendon transfers not requiring significant power. PMID:27387076

  12. High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

    PubMed

    Patterson, Jennifer Megan M

    2016-05-01

    Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. PMID:27094893

  13. Improved Peripheral Nerve Regeneration Using Acellular Nerve Allografts Loaded with Platelet-Rich Plasma

    PubMed Central

    Zheng, Canbin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping

    2014-01-01

    Acellular nerve allografts (ANAs) behave in a similar manner to autografts in supporting axonal regeneration in the repair of short peripheral nerve defects but fail in larger defects. The objective of this article is to evaluate the effect of ANA supplemented with platelet-rich plasma (PRP) to improve nerve regeneration after surgical repair and to discuss the mechanisms that underlie this approach. Autologous PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and the release of growth factors. Forty-eight Sprague–Dawley rats were randomly divided into 4 groups (12/group), identified as autograft, ANA, ANA loaded with PRP (ANA+PRP), and ANA loaded with platelet-poor plasma (PPP, ANA+PPP). All grafts were implanted to bridge long-gap (15 mm) sciatic nerve defects. We found that PRP with a high platelet concentration exhibited a sustained release of growth factors. Twelve weeks after surgery, the autograft group displayed the highest level of reinnervation, followed by the ANA+PRP group. The ANA+PRP group showed a better electrophysiology response for amplitude and conduction velocity than the ANA and ANA+PPP groups. Based on histological evaluation, the ANA+PRP and autograft groups had higher numbers of regenerating nerve fibers. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that PRP boosted expression of neurotrophins in the regenerated nerves. Moreover, the ANA+PRP and autograft groups showed excellent physiological outcomes in terms of the prevention of muscle atrophy. In conclusion, ANAs loaded with PRP as tissue-engineered scaffolds can enhance nerve regeneration and functional recovery after the repair of large nerve gaps nearly as well as autografts. PMID:24901030

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

    PubMed

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

    2015-02-20

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

  15. Ulnar nerve dysfunction

    MedlinePlus

    ... pressure on the elbow An elbow fracture or dislocation Temporary pain and tingling of this nerve can ... Saunders; 2011:chap 428. Read More Broken bone Dislocation Mononeuritis multiplex Mononeuropathy Myelin Peripheral neuropathy Systemic Update ...

  16. Diabetic Nerve Problems

    MedlinePlus

    ... at the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get ... you change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. ...

  17. Ulnar nerve dysfunction

    MedlinePlus

    ... surface of the body where it crosses the elbow. The damage destroys the nerve covering ( myelin sheath) ... be caused by: Long-term pressure on the elbow An elbow fracture or dislocation Temporary pain and ...

  18. Degenerative Nerve Diseases

    MedlinePlus

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

  19. Common peroneal nerve dysfunction

    MedlinePlus

    ... people: Who are very thin (for example, from anorexia nervosa ) Who have certain autoimmune conditions, such as ... Elsevier; 2013:chap 22. Read More Alertness - decreased Anorexia Broken bone Diabetes and nerve damage Mononeuritis multiplex ...

  20. Femoral nerve dysfunction

    MedlinePlus

    ... An abnormal knee reflex Smaller than normal quadriceps muscles on the front of the thigh Tests that may be done include: Electromyography ( EMG ) Nerve conduction tests ( NCV ), usually done at ...

  1. Femoral nerve dysfunction

    MedlinePlus

    Neuropathy - femoral nerve; Femoral neuropathy ... Craig EJ, Clinchot DM. Femoral neuropathy. In: Frontera WR, Silver JK, Rizzo TD Jr, eds. Essentials of Physical Medicine and Rehabilitation: Musculoskeletal Disorders, Pain, and Rehabilitation . 3rd ...

  2. Diabetic Nerve Problems

    MedlinePlus

    ... the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get it. ... change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. Controlling ...

  3. Schwannoma of Extraocular Nerves

    PubMed Central

    Niazi, Wasim; Boggan, James E.

    1994-01-01

    An unusual case of schwannoma arising from the third cranial nerve in a thirteen year old male is reported. The patient presented with paresis of the right oculomotor nerve and ipsilateral hemiparesis. The clinical features of this case are discussed and the pertinent medical literature reviewed. ImagesFigure 1p220-bFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:17171175

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

    SciTech Connect

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

    2015-02-20

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

  5. Sural nerve defects after nerve biopsy or nerve transfer as a sensory regeneration model for peripheral nerve conduit implantation.

    PubMed

    Radtke, C; Kocsis, J D; Reimers, K; Allmeling, C; Vogt, P M

    2013-09-01

    Nerve repair after injury can be effectively accomplished by direct suture approximation of the proximal and distal segments. This is more successful if coadaptation can be achieved without tension. Currently, the gold standard repair of larger deficits is the transplantation of an autologous sensory sural nerve graft. However, a significant disadvantage of this technique is the inevitable donor morbidity (sensory loss, neuroma and scar formation) after harvesting of the sural nerve. Moreover, limitation of autologous donor nerve length and fixed diameter of the available sural nerve are major drawbacks of current autograft treatment. Another approach that was introduced for nerve repair is the implantation of alloplastic nerve tubes made of, for example, poly-L-lactide. In these, nerve stumps of the transected nerves are surgically bridged using the biosynthetic conduit. A number of experimental studies, primarily in rodents, indicate axonal regeneration and remyelination after implantation of various conduits. However, only limited clinical studies with conduit implantation have been performed in acute peripheral nerve injuries particularly on digital nerves. Clinical transfer of animal studies, which can be carefully calibrated for site and extent of injury, to humans is difficult to interpret due to the intrinsic variability in human nerve injuries. This prevents effective quantification of improvement and induces bias in the study. Therefore, standardization of lesion/repair in human studies is warranted. Here we propose to use sural nerve defects, induced due to nerve graft harvesting or from diagnostic nerve biopsies as a model site to enable standardization of nerve conduit implantation. This would help better with the characterization of the implants and its effectiveness in axonal regeneration and remyelination. Nerve regeneration can be assessed, for example, by recovery of sensation, measured non-invasively by threshold to von Frey filaments and cold

  6. Biomaterials for the Development of Peripheral Nerve Guidance Conduits

    PubMed Central

    Nectow, Alexander R.; Marra, Kacey G.

    2012-01-01

    Currently, surgical treatments for peripheral nerve injury are less than satisfactory. The gold standard of treatment for peripheral nerve gaps >5 mm is the autologous nerve graft; however, this treatment is associated with a variety of clinical complications, such as donor site morbidity, limited availability, nerve site mismatch, and the formation of neuromas. Despite many recent advances in the field, clinical studies implementing the use of artificial nerve guides have yielded results that are yet to surpass those of autografts. Thus, the development of a nerve guidance conduit, which could match the effectiveness of the autologous nerve graft, would be beneficial to the field of peripheral nerve surgery. Design strategies to improve surgical outcomes have included the development of biopolymers and synthetic polymers as primary scaffolds with tailored mechanical and physical properties, luminal “fillers” such as laminin and fibronectin as secondary internal scaffolds, surface micropatterning, stem cell inclusion, and controlled release of neurotrophic factors. The current article highlights approaches to peripheral nerve repair through a channel or conduit, implementing chemical and physical growth and guidance cues to direct that repair process. PMID:21812591

  7. Intraneural Venous Malformations of the Median Nerve

    PubMed Central

    González Rodríguez, Alba; Midón Míguez, José

    2016-01-01

    Venous malformations arising from the peripheral nerve are a rare type of vascular malformation. We present the first case of an intraneural venous malformation of the median nerve to be reported in a child and review the previous two cases of median nerve compression due to a venous malformation that have been reported. These cases presented with painless masses in the volar aspect of the wrist or with symptoms suggestive of carpal tunnel syndrome. Clinical suspicion should lead to the use of Doppler ultrasonography as the first-line diagnostic tool. Magnetic resonance imaging and histopathology can confirm the diagnosis, as phleboliths are pathognomonic of venous malformations. Surgical treatment appears to be the only modality capable of successfully controlling the growth of an intraneural malformation. Sclerotherapy and radiotherapy have never been used to treat this type of malformation. PMID:27462571

  8. Molecular signaling and pulpal nerve development.

    PubMed

    Fried, K; Nosrat, C; Lillesaar, C; Hildebrand, C

    2000-01-01

    The purpose of this review is to discuss molecular factors influencing nerve growth to teeth. The establishment of a sensory pulpal innervation occurs concurrently with tooth development. Epithelial/mesenchymal interactions initiate the tooth primordium and change it into a complex organ. The initial events seem to be controlled by the epithelium, and subsequently, the mesenchyme acquires odontogenic properties. As yet, no single initiating epithelial or mesenchymal factor has been identified. Axons reach the jaws before tooth formation and form terminals near odontogenic sites. In some species, local axons have an initiating function in odontogenesis, but it is not known if this is also the case with mammals. In diphyodont mammals, the primary dentition is replaced by a permanent dentition, which involves a profound remodeling of terminal pulpal axons. The molecular signals underlying this remodeling remain unknown. Due to the senescent deterioration of the dentition, the target area of tooth nerves shrinks with age, and these nerves show marked pathological-like changes. Nerve growth factor and possibly also brain-derived neurotrophic factor seem to be important in the formation of a sensory pulpal innervation. Neurotrophin-3 and -4/5 are probably not involved. In addition, glial cell line-derived neurotrophic factor, but not neurturin, seems to be involved in the control of pulpal axon growth. A variety of other growth factors may also influence developing tooth nerves. Many major extracellular matrix molecules, which can influence growing axons, are present in developing teeth. It is likely that these molecules influence the growing pulpal axons. PMID:11021633

  9. Peptide growth factors, part B

    SciTech Connect

    Barnes, D.; Sirbasku, D.A.

    1987-01-01

    This book discusses the following topics: Platelet-Derived Growth Factor;Nerve and Glial Growth Factors;PC12 Pheochromocytoma Cells;Techniques for the Study of Growth Factor Activity;Genetic Approaches and Biological Effects.

  10. Exposure of nerve growth factor-treated PC12 rat pheochromocytoma cells to a modulated radiofrequency field at 836.55 MHz: Effects on c-jun and c-fos expression

    SciTech Connect

    Ivaschuk, O.I.; Jones, R.A.; Ishida-Jones, T.; Haggren, W.; Adey, W.R.; Phillips, J.L.

    1997-05-01

    Rat PC12 pheochromocytoma cells have been treated with nerve growth factor and then exposed to athermal levels of a packet-modulated radiofrequency field at 836.55 MHz. This signal was produced by a prototype time-domain multiple-access (TDMA) transmitter that conforms to the North American digital cellular telephone standard. Three slot average power densities were used: 0.09, 0.9, and 9 mW/cm{sup 2}. Exposures were for 20, 40, and 60 min and included an intermittent exposure regime, resulting in total incubation times of 20, 60, and 100 min, respectively. Concurrent controls were sham exposed. After extracting total cellular RNA, Northern blot analysis was used to assess the expression of the immediate early genes, c-fos and c-jun, in all cell populations. No change in c-fos transcript levels were detected after 20 min exposure at each field intensity. Transcript levels for c-jun were altered only after 20 min exposure to 9 mW/cm{sup 2}. 51 refs., 2 tabs.

  11. Exposure of nerve growth factor-treated PC12 rat pheochromocytoma cells to a modulated radiofrequency field at 836.55 MHz: effects on c-jun and c-fos expression.

    PubMed

    Ivaschuk, O I; Jones, R A; Ishida-Jones, T; Haggren, W; Adey, W R; Phillips, J L

    1997-01-01

    Rat PC12 pheochromocytoma cells have been treated with nerve growth factor and then exposed to athermal levels of a packet-modulated radiofrequency field at 836.55 MHz. This signal was produced by a prototype time-domain multiple-access (TDMA) transmitter that conforms to the North American digital cellular telephone standard. Three slot average power densities were used: 0.09, 0.9, and 9 mW/cm2. Exposures were for 20, 40, and 60 min and included an intermittent exposure regimen (20 min on/20 min off), resulting in total incubation times of 20, 60, and 100 min, respectively. Concurrent controls were sham exposed. After extracting total cellular RNA, Northern blot analysis was used to assess the expression of the immediate early genes, c-fos and c-jun, in all cell populations. No change in c-fos transcript levels were detected after 20 min exposure at each field intensity (20 min was the only time period at which c-fos message could be detected consistently). Transcript levels for c-jun were altered only after 20 min exposure to 9 mW/cm2 (average 38% decrease). PMID:9096840

  12. Ultrasound in Dual Nerve Impairment after Proximal Radial Nerve Lesion

    PubMed Central

    Lämmer, Alexandra B; Schwab, Stefan; Schramm, Axel

    2015-01-01

    Introduction Sonography in classical nerve entrapment syndromes is an established and validated method. In contrast, few publications highlight lesions of the radial nerve, particularly of the posterior interosseus nerve (PIN). Method Five patients with a radial nerve lesion were investigated by electromyography, nerve conduction velocity and ultrasound. Further normative values of 26 healthy subjects were evaluated. Results Four patients presented a clinical and electrophysiological proximal axonal radial nerve lesion and one patient showed a typical posterior interosseous nerve syndrome (PINS). The patient with PINS presented an enlargement of the PIN anterior to the supinator muscle. However four patients with proximal lesions showed an unexpected significant enlargement of the PIN within the supinator muscle. Conclusion High-resolution sonography is a feasible method to demonstrate the radial nerve including its distal branches. At least in axonal radial nerve lesions, sonography might reveal abnormalities far distant from a primary proximal lesion site clearly distinct from the appearance in classical PINS. PMID:25992766

  13. Peripheral nerve regeneration and neurotrophic factors

    PubMed Central

    TERENGHI, GIORGIO

    1999-01-01

    The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies. PMID:10227662

  14. Morphological response of injured adult rabbit optic nerve to implants containing media conditioned by growing optic nerves.

    PubMed

    Lavie, V; Harel, A; Doron, A; Solomon, A; Lobel, D; Belkin, M; Ben-Basat, S; Sharma, S; Schwartz, M

    1987-09-01

    Adult rabbit retina can express regeneration-associated characteristics after optic nerve injury, provided it is supplied with appropriate diffusible substances originating from media conditioned by regenerating fish optic nerves or by optic nerves of a newborn rabbit [Hadani et al., Proc. Natl. Acad. Sci. U.S.A., 81 (1984) 7965; Schwartz et al., Science, 228 (1985) 600]. This was shown by applying the active substances to the injured axons in the form of 'wrap-around' implants, consisting of collagen-coated silicone tubes which had been soaked in the conditioned media (CM). The regeneration-associated response was manifested biochemically and by sprouting of nerve fibers in culture. The present work provides morphological evidence that the implantation prolongs survival of ganglion cells and optic nerve fibers and induces new growth. Light microscopic analysis (using horseradish peroxidase (HRP) for labeling the fibers) revealed, 1 week following optic nerve injury, labeled fibers and ganglion cells in both the implanted and control (injured only or injured and implanted with collagen-coated silicone tubes free of CM) nerves. However, from the second week after the injury, distinct differences in the appearance of viable ganglion cells and labeled fibers, were seen between experimental and control preparations. In sections taken through the optic nerve, at the region distal to the site of injury, HRP-labeled fibers were seen in the experimental nerves 1 week, 2 weeks and to a significantly lesser extent 1 month after injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3676722

  15. [Biophysics of nerve excitation].

    PubMed

    Kol'e, O R; Maksimov, G V

    2010-01-01

    The studies testifying to the presence of the interrelation between the physiological functions of the organism and physical and chemical processes in nerves are discussed. Changes in some physical and chemical parameters observed both upon elicited rhythmic exaltation of nerves and during the spontaneous rhythmic activity of neurons are analyzed. Upon rhythmic exaltation, a complex of physical and chemical processes is triggered, and reversible structural and metabolic rearrangements at the subcellular and molecular levels occur that do not take place during the generation of a single action potential. Thus, only in conditions of rhythmic exaltation of a nerve, it is possible to reveal those processes that provide exaltation of nerves in the organism. The future possibilities of the investigations combining the biophysical and physiological approaches are substantiated. Characteristic changes in physicochemical parameters are observed in nerves during the generation of a series of action potentials of different frequency and duration ("frequency dependence") under normal physiological conditions, as well as in extreme situations and in nerve pathology. The structural and metabolic rearrangements are directly related to the mode of rhythmic exaltation and proceed both in the course of rhythmic exaltation and after its termination. Participation and the basic components of the nervous fulcrum (an axon, Shwan cell, myelin, subcellular organelles) in the realization of rhythmic exaltation is shown. In the coordination of all processes involved in rhythmic exaltation, the main role is played by the systems of redistribution and transport of intercellular and endocellular calcium. The idea is put forward that myelin of nerve fibers is not only an isolator, but also an "intercellular depot" of calcium and participates in the redistribution of different ions. Thus, the rhythmic excitation is of great importance in the realization of some physiological functions, the

  16. Direct Cranial Nerve Involvement by Gliomas: Case Series and Review of the Literature.

    PubMed

    Mabray, M C; Glastonbury, C M; Mamlouk, M D; Punch, G E; Solomon, D A; Cha, S

    2015-07-01

    Malignant gliomas are characterized by infiltrative growth of tumor cells, including along white matter tracts. This may result in clinical cranial neuropathy due to direct involvement of a cranial nerve rather than by leptomeningeal spread along cranial nerves. Gliomas directly involving cranial nerves III-XII are rare, with only 11 cases reported in the literature before 2014, including 8 with imaging. We present 8 additional cases demonstrating direct infiltration of a cranial nerve by a glioma. Asymmetric cisternal nerve expansion compared with the contralateral nerve was noted with a mean length of involvement of 9.4 mm. Based on our case series, the key imaging feature for recognizing direct cranial nerve involvement by a glioma is the detection of an intra-axial mass in the pons or midbrain that is directly associated with expansion, signal abnormality, and/or enhancement of the adjacent cranial nerves. PMID:25857757

  17. Effect of a high-intensity static magnetic field on sciatic nerve regeneration in the rat

    SciTech Connect

    Cordeiro, P.G.; Seckel, B.R.; Miller, C.D.; Gross, P.T.; Wise, R.E.

    1989-02-01

    The effect of a high-intensity static magnetic field on peripheral nerve regeneration is evaluated in rat sciatic nerve. Forty-four rats underwent sciatic nerve repair using polyethylene nerve guides. Postoperatively, the animals were exposed to a 1-tesla magnetic field for 12 hours per day for 4 weeks with appropriate controls. Our results demonstrate that a 1-tesla static magnetic field has no statistically significant effect on nerve regeneration as determined by myelinated axon counts and electrophysiologic studies. Also, the specific orientation of the sciatic nerve with respect to the magnetic field has no influence on axonal growth or nerve conduction. Periods of restraint of 12 hours per day for 4 weeks significantly inhibit weight gain but have no effect on peripheral nerve regeneration.

  18. Injection nerve palsy

    PubMed Central

    Kakati, Arindhom; Bhat, Dhananjaya; Devi, Bhagavathula Indira; Shukla, Dhaval

    2013-01-01

    Objective: To study the clinical profile and outcome of surgery for injection nerve palsies. Materials and Methods: This is a retrospective study of patients with INP who were treated at our institute during May 2000 to May 2009. Clinical, electroneuromyography (ENMG), and operative findings were noted. Intraoperative nerve action potential monitoring was not used in any case. Outcome of patients who were followed was reviewed. Results: INP comprised 92 (11%) of 837 nerve injury patients. Seventy one patients were children less than 16 years. The nerves involved were sciatic in 80 patients, radial in 8, and others in four. Fifty seven patients had power, grade 0/5. ENMG studies revealed absent compound muscle action potential in 64 and absent sensory nerve action potential in 67 patients. Thirty nine (42.3%) of 92 patients underwent surgery. The mean duration since injury in these patients was 5.2 months (3 months to 11 months). All underwent neurolysis. Only 18 patients who underwent surgery had a follow up of more than 3 months. Ten (55.5%) patients had good or fair outcome after surgery. Except for grade of motor deficit prior to surgery, none of the variables were found to significantly affect the outcome. Conclusion: The outcome of INP is generally good and many patients recover spontaneously. The outcome of surgery is dependent on preoperative motor power. PMID:23546341

  19. Barriers of the peripheral nerve

    PubMed Central

    Peltonen, Sirkku; Alanne, Maria; Peltonen, Juha

    2013-01-01

    This review introduces the traditionally defined anatomic compartments of the peripheral nerves based on light and electron microscopic topography and then explores the cellular and the most recent molecular basis of the different barrier functions operative in peripheral nerves. We also elucidate where, and how, the homeostasis of the normal human peripheral nerve is controlled in situ and how claudin-containing tight junctions contribute to the barriers of peripheral nerve. Also, the human timeline of the development of the barriers of the peripheral nerve is depicted. Finally, potential future therapeutic modalities interfering with the barriers of the peripheral nerve are discussed. PMID:24665400

  20. Fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve).

    PubMed

    Zeng, Rong; Frederick-Dyer, Katherine; Ferguson, N Lynn; Lewis, James; Fu, Yitong

    2012-09-01

    Fibrolipomatous hamartoma (FLH) is a rare, benign lesion of the peripheral nerves most frequently involving the median nerve and its digital branches (80 %). Pathognomonic MR features of FLH such as coaxial-cable-like appearance on axial planes and a spaghetti-like appearance on coronal planes have been described by Marom and Helms, obviating the need for diagnostic biopsy. We present a case of fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve) with associated subcutaneous fat proliferation. PMID:22526881

  1. What Are Nerve Blocks for Headache?

    MedlinePlus

    ... nerve blocks for headache? Print Email What are nerve blocks for headache? ACHE Newsletter Sign up for ... entering your e-mail address below. What are nerve blocks for headache? A nerve block is the ...

  2. Tissue engineered nerve constructs:where do we stand?

    PubMed Central

    Chalfoun, C T; Wirth, G A; Evans, G R D

    2006-01-01

    Driven by enormous clinical need, interest in peripheral nerve regeneration has become a prime focus of research and area of growth within the field of tissue engineering. While using autologous donor nerves for bridging peripheral defects remains today's gold standard, it remains associated with high donor site morbidity and lack of full recovery. This dictates research towards the development of biomimetic constructs as alternatives. Based on current concepts, this review summarizes various approaches including different extracellular martices, scaffolds, and growth factors that have been shown to promote migration and proliferation of Schwann cells. Since neither of these concepts in isolation is enough, although each is gaining increased interest to promote nerve regeneration, various combinations will need to be identified to strike a harmonious balance. Additional factors that must be incorporated into tissue engineered nerve constructs are also unknown and warrant further research efforts. It seems that future directions may allow us to determine the “missing link”. PMID:16796801

  3. Excess of Nerve Growth Factor in the Ovary Causes a Polycystic Ovary-Like Syndrome in Mice, which Closely Resembles Both Reproductive and Metabolic Aspects of the Human Syndrome

    PubMed Central

    Wilson, Jenny L.; Chen, Weiyi; Dissen, Gregory A.; Ojeda, Sergio R.; Cowley, Michael A.

    2014-01-01

    Polycystic ovarian syndrome (PCOS), the most common female endocrine disorder of unknown etiology, is characterized by reproductive abnormalities and associated metabolic conditions comprising insulin resistance, type 2 diabetes mellitus, and dyslipidemia. We previously reported that transgenic overexpression of nerve growth factor (NGF), a marker of sympathetic hyperactivity, directed to the ovary by the mouse 17α-hydroxylase/C17–20 lyase promoter (17NF mice), results in ovarian abnormalities similar to those seen in PCOS women. To investigate whether ovarian overproduction of NGF also induces common metabolic alterations of PCOS, we assessed glucose homeostasis by glucose tolerance test, plasma insulin levels, and body composition by dual-energy x-ray absorptiometry scan in young female 17NF mice and wild-type mice. 17NF mice exhibited increased body weight and alterations in body fat distribution with a greater accumulation of visceral fat compared with sc fat (P < .01). 17NF mice also displayed glucose intolerance (P < .01), decreased insulin-mediated glucose disposal (P < .01), and hyperinsulinemia (P < .05), which, similar to PCOS patients, occurred independently of body weight. Additionally, 17NF mice exhibited increased sympathetic outflow observed as increased interscapular brown adipose tissue temperature. This change was evident during the dark period (7 pm to 7 am) and occurred concomitant with increased interscapular brown adipose tissue uncoupling protein 1 expression. These findings suggest that overexpression of NGF in the ovary may suffice to cause both reproductive and metabolic alterations characteristic of PCOS and support the hypothesis that sympathetic hyperactivity may contribute to the development and/or progression of PCOS. PMID:25211588

  4. [Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

    PubMed

    Indo, Yasuhiro

    2015-05-01

    Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper. PMID:26211335

  5. Role of Ca2+ channels in the ability of membrane depolarization to prevent neuronal death induced by trophic-factor deprivation: evidence that levels of internal Ca2+ determine nerve growth factor dependence of sympathetic ganglion cells.

    PubMed Central

    Koike, T; Martin, D P; Johnson, E M

    1989-01-01

    Sympathetic neurons depend on nerve growth factor (NGF) for their survival both in vivo and in vitro; these cells die upon acute deprivation of NGF. We studied the effects of agents that cause membrane depolarization on neuronal survival after NGF deprivation. High-K+ medium (greater than or equal to 33 mM) prevented cell death; the effect of K+ was dose-dependent (EC50 = 21 mM). The protection by high K+ was abolished either by withdrawal of extracellular Ca2+ or by preloading the cells with a Ca2+ chelator. The involvement of Ca2+ flux across membranes in high-K+ saving of NGF-deprived neurons was also supported by experiments using Ca2+-channel antagonists and agonists. The Ca2+ antagonists nimodipine and nifedipine effectively blocked the survival-promoting effect of high K+. The Ca2+ agonists Bay K 8644 and (S)-202-791 did not by themselves save neurons from NGF deprivation but did strongly augment the effect of high K+; EC50 was shifted from 21 mM to 13 mM. These data suggest that dihydropyridine-sensitive L-type Ca2+ channels play a major role in the high-K+ saving. The depolarizing agents choline (EC50 = 1 mM) and carbamoylcholine (EC50 = 1 microM), acting through nicotinic cholinergic receptors, also rescued NGF-deprived neurons. The saving effect of nicotinic agonists was not blocked by withdrawal of extracellular Ca2+ but was counteracted by a chelator of intracellular Ca2+, suggesting the possible involvement of Ca2+ release from internal stores. Based on these findings we propose a "Ca2+ set-point hypothesis" for the degree of trophic-factor dependence of sympathetic neurons in vitro. Images PMID:2548215

  6. Optic nerve hypoplasia in children.

    PubMed Central

    Zeki, S. M.; Dutton, G. N.

    1990-01-01

    Optic nerve hypoplasia (ONH) is characterised by a diminished number of optic nerve fibres in the optic nerve(s) and until recently was thought to be rare. It may be associated with a wide range of other congenital abnormalities. Its pathology, clinical features, and the conditions associated with it are reviewed. Neuroendocrine disorders should be actively sought in any infant or child with bilateral ONH. Early recognition of the disorder may in some cases be life saving. Images PMID:2191713

  7. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  8. Optic Nerve Drusen

    MedlinePlus

    ... the drusen enlarge and the overlying tissue (nerve fiber layer) thins with age, the disc drusen become more apparent. How are optic disc drusen treated? There is no treatment for drusen. In the rare cases (with choroidal neovascularization) laser treatment may be indicated. Revised March 2016 Eye ...

  9. Optic Nerve Atrophy

    MedlinePlus

    ... with the occipital lobe (the part of the brain that interprets vision) like a cable wire. What is optic nerve ... nystagmus. In older patients, peripheral vision and color vision assessment ... around the brain and spinal cord (hydrocephalus) may prevent further optic ...

  10. The onset and rate of myelination in six peripheral and autonomic nerves of the rat.

    PubMed Central

    Schäfer, K; Friede, R L

    1988-01-01

    A light and electron microscopic study was carried out of the numbers of myelinated fibres in 6 nerves of the rat for 7 age groups from birth to 73 weeks. The hypoglossal nerve and the mandibular branch of the facial nerve had short and early myelination periods, essentially complete by the second week. The glossopharyngeal nerve and the sympathetic rami communicantes myelinated late and over a protracted period. Myelination of the rami communicantes continued up to 20 weeks, followed by a marked loss of fibres in the 73 week animals. Intercostal and saphenous nerves had intermediary patterns. There was evidence of subpopulations myelinating at different times. Measurements of myelin sheath thickness showed variations of relative sheath thickness with age, between nerves and for subpopulations of nerves. Late myelination corresponded to relatively thin myelin sheaths. Statistical two-stage-density cluster analysis by computer was used for analysing complex fibre populations. The developmental changes of three subpopulations of the intercostal nerve are documented. Nerves also differed in their rates of axon growth. The increment in axon calibre was small and late for sympathetic fibres. Intercostal and facial nerve fibres had rapid axon growth with different growth rates for subpopulations. PMID:3248966

  11. Decellularisation and histological characterisation of porcine peripheral nerves.

    PubMed

    Zilic, Leyla; Wilshaw, Stacy-Paul; Haycock, John W

    2016-09-01

    Peripheral nerve injuries affect a large proportion of the global population, often causing significant morbidity and loss of function. Current treatment strategies include the use of implantable nerve guide conduits (NGC's) to direct regenerating axons between the proximal and distal ends of the nerve gap. However, NGC's are limited in their effectiveness at promoting regeneration Current NGCs are not suitable as substrates for supporting either neuronal or Schwann cell growth, as they lack an architecture similar to that of the native extracellular matrix (ECM) of the nerve. The aim of this study was to create an acellular porcine peripheral nerve using a novel decellularisation protocol, in order to eliminate the immunogenic cellular components of the tissue, while preserving the three-dimensional histoarchitecture and ECM components. Porcine peripheral nerve (sciatic branches were decellularised using a low concentration (0.1%; w/v) sodium dodecyl sulphate in conjunction with hypotonic buffers and protease inhibitors, and then sterilised using 0.1% (v/v) peracetic acid. Quantitative and qualitative analysis revealed a ≥95% (w/w) reduction in DNA content as well as preservation of the nerve fascicles and connective tissue. Acellular nerves were shown to have retained key ECM components such as collagen, laminin and fibronectin. Slow strain rate to failure testing demonstrated the biomechanical properties of acellular nerves to be comparable to fresh controls. In conclusion, we report the production of a biocompatible, biomechanically functional acellular scaffold, which may have use in peripheral nerve repair. Biotechnol. Bioeng. 2016;113: 2041-2053. © 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc. PMID:26926914

  12. Dynamic regulation of Schwann cell enhancers after peripheral nerve injury.

    PubMed

    Hung, Holly A; Sun, Guannan; Keles, Sunduz; Svaren, John

    2015-03-13

    Myelination of the peripheral nervous system is required for axonal function and long term stability. After peripheral nerve injury, Schwann cells transition from axon myelination to a demyelinated state that supports neuronal survival and ultimately remyelination of axons. Reprogramming of gene expression patterns during development and injury responses is shaped by the actions of distal regulatory elements that integrate the actions of multiple transcription factors. We used ChIP-seq to measure changes in histone H3K27 acetylation, a mark of active enhancers, to identify enhancers in myelinating rat peripheral nerve and their dynamics after demyelinating nerve injury. Analysis of injury-induced enhancers identified enriched motifs for c-Jun, a transcription factor required for Schwann cells to support nerve regeneration. We identify a c-Jun-bound enhancer in the gene for Runx2, a transcription factor induced after nerve injury, and we show that Runx2 is required for activation of other induced genes. In contrast, enhancers that lose H3K27ac after nerve injury are enriched for binding sites of the Sox10 and early growth response 2 (Egr2/Krox20) transcription factors, which are critical determinants of Schwann cell differentiation. Egr2 expression is lost after nerve injury, and many Egr2-binding sites lose H3K27ac after nerve injury. However, the majority of Egr2-bound enhancers retain H3K27ac, indicating that other transcription factors maintain active enhancer status after nerve injury. The global epigenomic changes in H3K27ac deposition pinpoint dynamic changes in enhancers that mediate the effects of transcription factors that control Schwann cell myelination and peripheral nervous system responses to nerve injury. PMID:25614629

  13. Ultrasound of Peripheral Nerves

    PubMed Central

    Suk, Jung Im; Walker, Francis O.; Cartwright, Michael S.

    2013-01-01

    Over the last decade, neuromuscular ultrasound has emerged as a useful tool for the diagnosis of peripheral nerve disorders. This article reviews sonographic findings of normal nerves including key quantitative ultrasound measurements that are helpful in the evaluation of focal and possibly generalized peripheral neuropathies. It also discusses several recent papers outlining the evidence base for the use of this technology, as well as new findings in compressive, traumatic, and generalized neuropathies. Ultrasound is well suited for use in electrodiagnostic laboratories where physicians, experienced in both the clinical evaluation of patients and the application of hands-on technology, can integrate findings from the patient’s history, physical examination, electrophysiological studies, and imaging for diagnosis and management. PMID:23314937

  14. Cranial Nerve II: Vision.

    PubMed

    Gillig, Paulette Marie; Sanders, Richard D

    2009-09-01

    This article contains a brief review of the anatomy of the visual system, a survey of diseases of the retina, optic nerve and lesions of the optic chiasm, and other visual field defects of special interest to the psychiatrist. It also includes a presentation of the corticothalamic mechanisms, differential diagnosis, and various manifestations of visual illusions, and simple and complex visual hallucinations, as well as the differential diagnoses of these various visual phenomena. PMID:19855858

  15. Optic nerve hypoplasia.

    PubMed

    Kaur, Savleen; Jain, Sparshi; Sodhi, Harsimrat B S; Rastogi, Anju; Kamlesh

    2013-05-01

    Optic nerve hypoplasia (ONH) is a congenital anomaly of the optic disc that might result in moderate to severe vision loss in children. With a vast number of cases now being reported, the rarity of ONH is obviously now refuted. The major aspects of ophthalmic evaluation of an infant with possible ONH are visual assessment, fundus examination, and visual electrophysiology. Characteristically, the disc is small, there is a peripapillary double-ring sign, vascular tortuosity, and thinning of the nerve fiber layer. A patient with ONH should be assessed for presence of neurologic, radiologic, and endocrine associations. There may be maternal associations like premature births, fetal alcohol syndrome, maternal diabetes. Systemic associations in the child include endocrine abnormalities, developmental delay, cerebral palsy, and seizures. Besides the hypoplastic optic nerve and chiasm, neuroimaging shows abnormalities in ventricles or white- or gray-matter development, septo-optic dysplasia, hydrocephalus, and corpus callosum abnormalities. There is a greater incidence of clinical neurologic abnormalities in patients with bilateral ONH (65%) than patients with unilateral ONH. We present a review on the available literature on the same to urge caution in our clinical practice when dealing with patients with ONH. Fundus photography, ocular coherence tomography, visual field testing, color vision evaluation, neuroimaging, endocrinology consultation with or without genetic testing are helpful in the diagnosis and management of ONH. (Method of search: MEDLINE, PUBMED). PMID:24082663

  16. Growth

    NASA Astrophysics Data System (ADS)

    Waag, Andreas

    This chapter is devoted to the growth of ZnO. It starts with various techniques to grow bulk samples and presents in some detail the growth of epitaxial layers by metal organic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), and pulsed laser deposition (PLD). The last section is devoted to the growth of nanorods. Some properties of the resulting samples are also presented. If a comparison between GaN and ZnO is made, very often the huge variety of different growth techniques available to fabricate ZnO is said to be an advantage of this material system. Indeed, growth techniques range from low cost wet chemical growth at almost room temperature to high quality MOCVD growth at temperatures above 1, 000∘C. In most cases, there is a very strong tendency of c-axis oriented growth, with a much higher growth rate in c-direction as compared to other crystal directions. This often leads to columnar structures, even at relatively low temperatures. However, it is, in general, not straight forward to fabricate smooth ZnO thin films with flat surfaces. Another advantage of a potential ZnO technology is said to be the possibility to grow thin films homoepitaxially on ZnO substrates. ZnO substrates are mostly fabricated by vapor phase transport (VPT) or hydrothermal growth. These techniques are enabling high volume manufacturing at reasonable cost, at least in principle. The availability of homoepitaxial substrates should be beneficial to the development of ZnO technology and devices and is in contrast to the situation of GaN. However, even though a number of companies are developing ZnO substrates, only recently good quality substrates have been demonstrated. However, these substrates are not yet widely available. Still, the situation concerning ZnO substrates seems to be far from low-cost, high-volume production. The fabrication of dense, single crystal thin films is, in general, surprisingly difficult, even when ZnO is grown on a ZnO substrate. However

  17. ‘Strategic Sequences’ in Adipose Derived Stem Cell Nerve Regeneration

    PubMed Central

    Widgerow, Alan D.; Salibian, Ara A.; Kohan, Emil; SartiniFerreira, Tadeu; Afzel, Hassaan; Tham, Thanh; Evans, Gregory RD

    2014-01-01

    Background Peripheral nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques utilizing human adipose derived stem cells (hADSCs) for nerve regeneration, and derive a comprehensive approach to hADSC therapy for PNI. Methods A literature review was conducted using the electronic database PubMed to search for current experimental approaches to repairing peripheral nerve injuries using hADSCs. Key search elements focused on specific components of nerve regeneration paradigms, including, 1) support cells, 2) scaffolds and 3) nerve conduits. Results Strategic sequences were developed by optimizing the components of different experimental regenerative therapies. These sequences focus on priming hADSCs within a specialized growth medium, a hydrogel matrix base, and a collagen nerve conduit to achieve neuromodulatory nerve regeneration. Human ADSCs may exert their neuroregenerative influence through paracrine effects on surrounding Schwann cells in addition to physical interactions with injured tissue. Conclusions hADSCs may play a key role in nerve regeneration by acting primarily as support for local neurotrophic mediation and modulation of nerve growth rather than that of a primary neuronal differentiation agent. PMID:24375471

  18. Neuromuscular Ultrasound of Cranial Nerves

    PubMed Central

    Tawfik, Eman A.; Cartwright, Michael S.

    2015-01-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed. PMID:25851889

  19. Improved peripheral nerve regeneration in streptozotocin-induced diabetic rats by oral lumbrokinase.

    PubMed

    Lee, Han-Chung; Hsu, Yuan-Man; Tsai, Chin-Chuan; Ke, Cherng-Jyh; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2015-01-01

    We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I-II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery. PMID:25787300

  20. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    PubMed Central

    Zhao, Qun; Li, Zhi-yue; Zhang, Ze-peng; Mo, Zhou-yun; Chen, Shi-jie; Xiang, Si-yu; Zhang, Qing-shan; Xue, Min

    2015-01-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury. PMID:26604912

  1. Ultrasound guidance of uncommon nerve blocks

    PubMed Central

    Thallaj, Ahmed

    2011-01-01

    In the past nerve stimulation was considered the standard tool for anesthesiologists to locate the peripheral nerve for nerve blocks. However, with the recent introduction of ultrasound (US) technology for regional anesthesia, the use of nerve stimulation has become a rarity nowadays. There is a growing interest by most anesthesiologists in using US for nerve blocks because of its simplicity and accuracy. US is now available in most hospitals practicing regional anesthesia and is a popular tool for performance of nerve blocks. Although nerve stimulation became a rarity, however the use of it is now limited to identify small nerve structures, such as greater auricular nerve and medial antebrachial cutaneous nerve of the forearm. However, in this review article we discuss the role of ultrasonography for greater auricular and antebrachial cutaneous nerve blocks, which could replace nerve stimulation technique. We look at the available literature on the role of US for the performance of uncommon nerve blocks and its benefits. PMID:22144927

  2. Nerve blocks for chronic pain.

    PubMed

    Hayek, Salim M; Shah, Atit

    2014-10-01

    Nerve blocks are often performed as therapeutic or palliative interventions for pain relief. However, they are often performed for diagnostic or prognostic purposes. When considering nerve blocks for chronic pain, clinicians must always consider the indications, risks, benefits, and proper technique. Nerve blocks encompass a wide variety of interventional procedures. The most common nerve blocks for chronic pain and that may be applicable to the neurosurgical patient population are reviewed in this article. This article is an introduction and brief synopsis of the different available blocks that can be offered to a patient. PMID:25240668

  3. Nerve conduction and electromyography studies.

    PubMed

    Kane, N M; Oware, A

    2012-07-01

    Nerve conduction studies (NCS) and electromyography (EMG), often shortened to 'EMGs', are a useful adjunct to clinical examination of the peripheral nervous system and striated skeletal muscle. NCS provide an efficient and rapid method of quantifying nerve conduction velocity (CV) and the amplitude of both sensory nerve action potentials (SNAPs) and compound motor action potentials (cMAPs). The CV reflects speed of propagation of action potentials, by saltatory conduction, along large myelinated axons in a peripheral nerve. The amplitude of SNAPs is in part determined by the number of axons in a sensory nerve, whilst amplitude of cMAPs reflects integrated function of the motor axons, neuromuscular junction and striated muscle. Repetitive nerve stimulation (RNS) can identify defects of neuromuscular junction (NMJ) transmission, pre- or post-synaptic. Needle EMG examination can detect myopathic changes in muscle and signs of denervation. Combinations of these procedures can establish if motor and/or sensory nerve cell bodies or peripheral nerves are damaged (e.g. motor neuronopathy, sensory ganglionopathy or neuropathy), and also indicate if the primary target is the axon or the myelin sheath (i.e. axonal or demyelinating neuropathies). The distribution of nerve damage can be determined as either generalised, multifocal (mononeuropathy multiplex) or focal. The latter often due to compression at the common entrapment sites (such as the carpal tunnel, Guyon's canal, cubital tunnel, radial groove, fibular head and tarsal tunnel, to name but a few of the reported hundred or so 'entrapment neuropathies'). PMID:22614870

  4. Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model.

    PubMed

    Wang, Chau-Zen; Chen, Yi-Jen; Wang, Yan-Hsiung; Yeh, Ming-Long; Huang, Mao-Hsiung; Ho, Mei-Ling; Liang, Jen-I; Chen, Chia-Hsin

    2014-01-01

    The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm(2) and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm(2). Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm(2) had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm(2). Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm(2). Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic nerve regeneration following a crush injury. PMID:25119457

  5. Nerve-pulse interactions

    SciTech Connect

    Scott, A.C.

    1982-01-01

    Some recent experimental and theoretical results on mechanisms through which individual nerve pulses can interact are reviewed. Three modes of interactions are considered: (1) interaction of pulses as they travel along a single fiber which leads to velocity dispersion; (2) propagation of pairs of pulses through a branching region leading to quantum pulse code transformations; and (3) interaction of pulses on parallel fibers through which they may form a pulse assembly. This notion is analogous to Hebb's concept of a cell assembly, but on a lower level of the neural hierarchy.

  6. Characterization of a chondroitin sulfate hydrogel for nerve root regeneration.

    PubMed

    Conovaloff, Aaron; Panitch, Alyssa

    2011-10-01

    Brachial plexus injury is a serious medical problem that affects many patients annually, with most cases involving damage to the nerve roots. Therefore, a chondroitin sulfate hydrogel was designed to both serve as a scaffold for regenerating root neurons and deliver neurotrophic signals. Capillary electrophoresis showed that chondroitin sulfate has a dissociation constant in the micromolar range with several common neurotrophins, and this was determined to be approximately tenfold stronger than with heparin. It was also revealed that nerve growth factor exhibits a slightly stronger affinity for hyaluronic acid than for chondroitin sulfate. However, E8 chick dorsal root ganglia cultured in the presence of nerve growth factor revealed that ganglia cultured in chondroitin sulfate scaffolds showed more robust growth than those cultured in control gels of hyaluronic acid. It is hypothesized that, despite the stronger affinity of nerve growth factor for hyaluronic acid, chondroitin sulfate serves as a better scaffold for neurite outgrowth, possibly due to inhibition of growth by hyaluronic acid chains. PMID:21804177

  7. Characterization of a chondroitin sulfate hydrogel for nerve root regeneration

    NASA Astrophysics Data System (ADS)

    Conovaloff, Aaron; Panitch, Alyssa

    2011-10-01

    Brachial plexus injury is a serious medical problem that affects many patients annually, with most cases involving damage to the nerve roots. Therefore, a chondroitin sulfate hydrogel was designed to both serve as a scaffold for regenerating root neurons and deliver neurotrophic signals. Capillary electrophoresis showed that chondroitin sulfate has a dissociation constant in the micromolar range with several common neurotrophins, and this was determined to be approximately tenfold stronger than with heparin. It was also revealed that nerve growth factor exhibits a slightly stronger affinity for hyaluronic acid than for chondroitin sulfate. However, E8 chick dorsal root ganglia cultured in the presence of nerve growth factor revealed that ganglia cultured in chondroitin sulfate scaffolds showed more robust growth than those cultured in control gels of hyaluronic acid. It is hypothesized that, despite the stronger affinity of nerve growth factor for hyaluronic acid, chondroitin sulfate serves as a better scaffold for neurite outgrowth, possibly due to inhibition of growth by hyaluronic acid chains.

  8. Peripheral nerve conduits: technology update

    PubMed Central

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  9. Ultrasound-Guided Peripheral Nerve Procedures.

    PubMed

    Strakowski, Jeffrey A

    2016-08-01

    Ultrasound guidance allows real-time visualization of the needle in peripheral nerve procedures, improving accuracy and safety. Sonographic visualization of the peripheral nerve and surrounding anatomy can provide valuable information for diagnostic purposes and procedure enhancement. Common procedures discussed are the suprascapular nerve at the suprascapular notch, deep branch of the radial nerve at the supinator, median nerve at the pronator teres and carpal tunnel, lateral cutaneous nerve of the thigh, superficial fibular nerve at the leg, tibial nerve at the ankle, and interdigital neuroma. For each procedure, the indications, relevant anatomy, preprocedural scanning technique, and injection procedure itself are detailed. PMID:27468673

  10. The Impact of Type 1 Diabetes Mellitus on Corneal Epithelial Nerve Morphology and the Corneal Epithelium

    PubMed Central

    Cai, Daniel; Zhu, Meifang; Petroll, W. Matthew; Koppaka, Vindhya; Robertson, Danielle M.

    2015-01-01

    Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis. PMID:25102563

  11. The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium.

    PubMed

    Cai, Daniel; Zhu, Meifang; Petroll, W Matthew; Koppaka, Vindhya; Robertson, Danielle M

    2014-10-01

    Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis. PMID:25102563

  12. Neural tissue engineering options for peripheral nerve regeneration.

    PubMed

    Gu, Xiaosong; Ding, Fei; Williams, David F

    2014-08-01

    Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system. PMID:24818883

  13. Occipital nerve stimulation.

    PubMed

    Mammis, Antonios; Agarwal, Nitin; Mogilner, Alon Y

    2015-01-01

    Occipital nerve stimulation (ONS) is a form of neuromodulation therapy aimed at treating intractable headache and craniofacial pain. The therapy utilizes neurostimulating electrodes placed subcutaneously in the occipital region and connected to a permanently implanted programmable pulse generator identical to those used for dorsal column/spinal cord stimulation. The presumed mechanisms of action involve modulation of the trigeminocervical complex, as well as closure of the physiologic pain gate. ONS is a reversible, nondestructive therapy, which can be tailored to a patient's individual needs. Typically, candidates for successful ONS include those patients with migraines, Chiari malformation, or occipital neuralgia. However, recent MRSA infections, unrealistic expectations, and psychiatric comorbidities are generally contraindications. As with any invasive procedure, complications may occur including lead migration, infection, wound erosion, device failure, muscle spasms, and pain. The success of this therapy is dependent on careful patient selection, a preimplantation trial, meticulous implantation technique, programming strategies, and complication avoidance. PMID:25411143

  14. Restorative effect and mechanism of mecobalamin on sciatic nerve crush injury in mice.

    PubMed

    Gan, Lin; Qian, Minquan; Shi, Keqin; Chen, Gang; Gu, Yanglin; Du, Wei; Zhu, Guoxing

    2014-11-15

    Mecobalamin, a form of vitamin B12 containing a central metal element (cobalt), is one of the most important mediators of nervous system function. In the clinic, it is often used to accelerate recovery of peripheral nerves, but its molecular mechanism remains unclear. In the present study, we performed sciatic nerve crush injury in mice, followed by daily intraperitoneal administration of mecobalamin (65 μg/kg or 130 μg/kg) or saline (negative control). Walking track analysis, histomorphological examination, and quantitative real-time PCR showed that mecobalamin significantly improved functional recovery of the sciatic nerve, thickened the myelin sheath in myelinated nerve fibers, and increased the cross-sectional area of target muscle cells. Furthermore, mecobalamin upregulated mRNA expression of growth associated protein 43 in nerve tissue ipsilateral to the injury, and of neurotrophic factors (nerve growth factor, brain-derived nerve growth factor and ciliary neurotrophic factor) in the L4-6 dorsal root ganglia. Our findings indicate that the molecular mechanism underlying the therapeutic effect of mecobalamin after sciatic nerve injury involves the upregulation of multiple neurotrophic factor genes. PMID:25598780

  15. Restorative effect and mechanism of mecobalamin on sciatic nerve crush injury in mice

    PubMed Central

    Gan, Lin; Qian, Minquan; Shi, Keqin; Chen, Gang; Gu, Yanglin; Du, Wei; Zhu, Guoxing

    2014-01-01

    Mecobalamin, a form of vitamin B12 containing a central metal element (cobalt), is one of the most important mediators of nervous system function. In the clinic, it is often used to accelerate recovery of peripheral nerves, but its molecular mechanism remains unclear. In the present study, we performed sciatic nerve crush injury in mice, followed by daily intraperitoneal administration of mecobalamin (65 μg/kg or 130 μg/kg) or saline (negative control). Walking track analysis, histomorphological examination, and quantitative real-time PCR showed that mecobalamin significantly improved functional recovery of the sciatic nerve, thickened the myelin sheath in myelinated nerve fibers, and increased the cross-sectional area of target muscle cells. Furthermore, mecobalamin upregulated mRNA expression of growth associated protein 43 in nerve tissue ipsilateral to the injury, and of neurotrophic factors (nerve growth factor, brain-derived nerve growth factor and ciliary neurotrophic factor) in the L4–6 dorsal root ganglia. Our findings indicate that the molecular mechanism underlying the therapeutic effect of mecobalamin after sciatic nerve injury involves the upregulation of multiple neurotrophic factor genes. PMID:25598780

  16. Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration†

    PubMed Central

    Wood, Matthew D.; Moore, Amy M.; Hunter, Daniel A.; Tuffaha, Sami; Borschel, Gregory H.; Mackinnon, Susan E.; Sakiyama-Elbert, Shelly E.

    2008-01-01

    Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries. PMID:19103514

  17. Malignant Peripheral Nerve Sheath Tumor.

    PubMed

    James, Aaron W; Shurell, Elizabeth; Singh, Arun; Dry, Sarah M; Eilber, Fritz C

    2016-10-01

    Malignant peripheral nerve sheath tumor (MPNST) is the sixth most common type of soft tissue sarcoma. Most MPNSTs arise in association with a peripheral nerve or preexisting neurofibroma. Neurofibromatosis type is the most important risk factor for MPNST. Tumor size and fludeoxyglucose F 18 avidity are among the most helpful parameters to distinguish MPNST from a benign peripheral nerve sheath tumor. The histopathologic diagnosis is predominantly a diagnosis of light microscopy. Immunohistochemical stains are most helpful to distinguish high-grade MPNST from its histologic mimics. Current surgical management of high-grade MPNST is similar to that of other high-grade soft tissue sarcomas. PMID:27591499

  18. Nerve Transfers for the Restoration of Wrist, Finger, and Thumb Extension After High Radial Nerve Injury.

    PubMed

    Pet, Mitchell A; Lipira, Angelo B; Ko, Jason H

    2016-05-01

    High radial nerve injury is a common pattern of peripheral nerve injury most often associated with orthopedic trauma. Nerve transfers to the wrist and finger extensors, often from the median nerve, offer several advantages when compared to nerve repair or grafting and tendon transfer. In this article, we discuss the forearm anatomy pertinent to performing these nerve transfers and review the literature surrounding nerve transfers for wrist, finger, and thumb extension. A suggested algorithm for management of acute traumatic high radial nerve palsy is offered, and our preferred surgical technique for treatment of high radial nerve palsy is provided. PMID:27094891

  19. Nerve Disease and Bladder Control

    MedlinePlus

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... KB) Alternate Language URL Nerve Disease and Bladder Control Page Content On this page: What bladder control ...

  20. Ion Channels in Nerve Membranes

    ERIC Educational Resources Information Center

    Ehrenstein, Gerald

    1976-01-01

    Discusses research that indicates that nerve membranes, which play a key role in the conduction of impulses, are traversed by protein channels with ion pathways opened and closed by the membrane electric field. (Author/MLH)

  1. Imaging of the facial nerve.

    PubMed

    Veillona, F; Ramos-Taboada, L; Abu-Eid, M; Charpiot, A; Riehm, S

    2010-05-01

    The facial nerve is responsible for the motor innervation of the face. It has a visceral motor function (lacrimal, submandibular, sublingual glands and secretion of the nose); it conveys a great part of the taste fibers, participates to the general sensory of the auricle (skin of the concha) and the wall of the external auditory meatus. The facial mimic, production of tears, nasal flow and salivation all depend on the facial nerve. In order to image the facial nerve it is mandatory to be knowledgeable about its normal anatomy including the course of its efferent and afferent fibers and about relevant technical considerations regarding CT and MR to be able to achieve high-resolution images of the nerve. PMID:20456888

  2. An inside-out vein graft filled with platelet-rich plasma for repair of a short sciatic nerve defect in rats.

    PubMed

    Kim, Ji Yeong; Jeon, Woo Joo; Kim, Dong Hwee; Rhyu, Im Joo; Kim, Young Hwan; Youn, Inchan; Park, Jong Woong

    2014-07-15

    Platelet-rich plasma containing various growth factors can promote nerve regeneration. An inside-out vein graft can substitute nerve autograft to repair short nerve defects. It is hypothesized that an inside-out vein graft filled with platelet-rich plasma shows better effects in the repair of short sciatic nerve defects. In this study, an inside-out vein autograft filled with platelet-rich plasma was used to bridge a 10 mm-long sciatic nerve defect in rats. The sciatic nerve function of rats with an inside-out vein autograft filled with platelet-rich plasma was better improved than that of rats with a simple inside-out vein autograft. At 6 and 8 weeks, the sciatic nerve function of rats with an inside-out vein autograft filled with platelet-rich plasma was better than that of rats undergoing nerve autografting. Compared with the sciatic nerve repaired with a simple inside-out vein autograft, the number of myelinated axons was higher, axon diameter and myelin sheath were greater in the sciatic nerve repaired with an inside-out vein autograft filled with platelet-rich plasma and they were similar to those in the sciatic nerve repaired with nerve autograft. These findings suggest that an inside-out vein graft filled with platelet-rich plasma can substitute nerve autograft to repair short sciatic nerve defects. PMID:25221591

  3. Size-related differences in the branching pattern of the motor nerve terminals in triangularis sterni muscle of the mouse.

    PubMed

    Tomasi, J; Fenol, R; Santafe, M; Mayayo, E

    1989-01-01

    A light microscopy morphometric study was performed in singly innervated synaptic areas of the triangularis sterni muscle of the normal adult Swiss mouse. Investigating mechanisms of the motor nerve growth control, we tested the hypothesis that significant differences in the nerve terminal branching pattern can be detected between different populations of nerve endings classified according to their arborization complexity or size. The main observations of this morphometric study are first, that the mean segment length of the terminal arborization between branch points behaves as an independent variable from the remaining parameters; the mean value of this parameter did not change in nerve endings of differing size and complexity. Secondly, the increase in size of the nerve endings is accompanied by a significant reduction in the mean length of the distal free-end segments. Results are discussed in the context of the possible regulatory mechanisms governing nerve terminal growth and remodelling. PMID:2752213

  4. Hemangioma of the Facial Nerve

    PubMed Central

    Balkany, Thomas; Fradis, Milo; Jafek, Bruce W.; Rucker, Nolan C.

    1991-01-01

    Hemangioma of the facial nerve may occur more frequently than previously recognized. This benign vascular tumor most often arises in the area of the geniculate ganglion, although the reason for this site of predilection is not known. Using silicon injection and cross-sectional vessel counts, we recently demonstrated the presence of a geniculate capillary plexus (GCP) in the cat. The present study was designed to identify a similar GCP in man, if present, and to relate if to the site of predilection of hemangioma of the facial nerve. Twenty-five human facial nerves were studied in horizontally sectioned temporal bones. A clinical case of hemangioma arising at the geniculate ganglion is presented. The human geniculate ganglion has a very rich capillary plexus in contrast to the poor intrinsic vasculature of the adjacent labyrinthine segment and nioderate vasculature of the tympanic segment of the facial nerve. We hypothesize that the GCP is the origin of most hemangiomas of facial nerve. The anatomic distinctness of the geniculate gangion and GCP from the facial nerve may allow removal of these tumors with preservation of motor function in certain cases. ImagesFigure 1Figure 2Figure 3 PMID:17170823

  5. [Peripheral Nerve Injuries in Sports].

    PubMed

    Tettenborn, B; Mehnert, S; Reuter, I

    2016-09-01

    Peripheral nerve injuries due to sports are relatively rare but the exact incidence is not known due to a lack of epidemiological studies. Particular sports activities tend to cause certain peripheral nerve injuries including direct acute compression or stretching, repetitive compression and stretching over time, or another mechanism such as ischemia or laceration. These nerve lesions may be severe and delay or preclude the athlete's return to sports, especially in cases with delayed diagnosis. Repetitive and vigorous use or overuse makes the athlete vulnerable to disorders of the peripheral nerves, and sports equipment may cause compression of the nerves. Depending on etiology, the treatment is primarily conservative and includes physiotherapy, modification of movements and sports equipment, shoe inserts, splinting, antiphlogistic drugs, sometimes local administration of glucocorticoids or, lately, the use of extracorporeal shock waves. Most often, cessation of the offending physical activity is necessary. Surgery is only indicated in the rare cases of direct traumatic nerve injury or when symptoms are refractory to conservative therapy. Prognosis mainly depends on the etiology and the available options of modifying measures.This article is based on the publications "Reuter I, Mehnert S. Engpasssyndrome peripherer Nerven bei Sportlern". Akt Neurol 2012;39:292-308 and Sportverl Sportschad 2013;27:130-146. PMID:27607069

  6. Electrospun poly(L-lactide-co-glycolide) biodegradable polymer nanofibre tubes for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Bini, T. B.; Gao, Shujun; Chyan Tan, Ter; Wang, Shu; Lim, Aymeric; Ben Hai, Lim; Ramakrishna, S.

    2004-11-01

    Nanotechnology is an area receiving increasing attention as progress is made towards tailoring the morphology of polymeric biomaterial for a variety of applications. In the present study an attempt was made to electrospin poly(L-lactide-co-glycolide) biodegradable polymer nanofibres. In this process, polymer fibres with diameters down to the nanometre range are formed by subjecting a fluid jet to a high electric field. The nanofibres were collected on to a rotating Teflon mandrel and fabricated to tubes or conduits, to function as nerve guidance channels. The feasibility of in vivo nerve regeneration was investigated through several of these conduits. The biological performance of the conduits were examined in the rat sciatic nerve model with a 10 mm gap length. After implantation of the nanofibre nerve guidance conduit to the right sciatic nerve of the rat, there was no inflammatory response. One month after implantation five out of eleven rats showed successful nerve regeneration. None of the implanted tubes showed tube breakage. The nanofibre nerve guidance conduits were flexible, permeable and showed no swelling. Thus, these new poly(L-lactide-co-glycolide) nanofibre conduits can be effective aids for nerve regeneration and repair. Improvements could be done by impregnating nerve growth factors or Schwann cells and may lead to clinical applications.

  7. Peripheral Nerve Regeneration Through Hydrogel-Enriched Chitosan Conduits Containing Engineered Schwann Cells for Drug Delivery.

    PubMed

    Meyer, Cora; Wrobel, Sandra; Raimondo, Stefania; Rochkind, Shimon; Heimann, Claudia; Shahar, Abraham; Ziv-Polat, Ofra; Geuna, Stefano; Grothe, Claudia; Haastert-Talini, Kirsten

    2016-01-01

    Critical length nerve defects in the rat sciatic nerve model were reconstructed with chitosan nerve guides filled with Schwann cells (SCs) containing hydrogel. The transplanted SCs were naive or had been genetically modified to overexpress neurotrophic factors, thus providing a cellular neurotrophic factor delivery system. Prior to the assessment in vivo, in vitro studies evaluating the properties of engineered SCs overexpressing glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF-2(18kDa)) demonstrated their neurite outgrowth inductive bioactivity for sympathetic PC-12 cells as well as for dissociated dorsal root ganglion cell drop cultures. SCs within NVR-hydrogel, which is mainly composed of hyaluronic acid and laminin, were delivered into the lumen of chitosan hollow conduits with a 5% degree of acetylation. The viability and neurotrophic factor production by engineered SCs within NVR-Gel inside the chitosan nerve guides was further demonstrated in vitro. In vivo we studied the outcome of peripheral nerve regeneration after reconstruction of 15-mm nerve gaps with either chitosan/NVR-Gel/SCs composite nerve guides or autologous nerve grafts (ANGs). While ANGs did guarantee for functional sensory and motor regeneration in 100% of the animals, delivery of NVR-Gel into the chitosan nerve guides obviously impaired sufficient axonal outgrowth. This obstacle was overcome to a remarkable extent when the NVR-Gel was enriched with FGF-2(18kDa) overexpressing SCs. PMID:25876520

  8. Verapamil inhibits scar formation after peripheral nerve repair in vivo

    PubMed Central

    Han, A-chao; Deng, Jing-xiu; Huang, Qi-shun; Zheng, Huai-yuan; Zhou, Pan; Liu, Zhi-wei; Chen, Zhen-bing

    2016-01-01

    The calcium channel blocker, verapamil, has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro. It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue. In this study, the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No. 10-0 suture. The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks. Compared with the control group (stoma wrapped with gelfoam soaked with physiological saline), the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo, suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons. These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair. PMID:27127494

  9. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

  10. The progress in optic nerve regeneration, where are we?

    PubMed Central

    Shum, Jennifer Wei Huen; Liu, Kai; So, Kwok-fai

    2016-01-01

    Optic nerve regeneration is an important area of research. It can be used to treat patients suffering from optic neuropathy and provides insights into the treatment of numerous neurodegenerative diseases. There are many hurdles impeding optic regeneration in mammals. The mammalian central nervous system is non-permissive to regeneration and intrinsically lacks the capacity for axonal regrowth. Any axonal injury also triggers a vicious cycle of apoptosis. Understanding these hurdles provides us with a rough framework to appreciate the essential steps to bring about optic nerve regeneration: enhancing neuronal survival, axon regeneration, remyelination and establishing functional synapses to the original neuronal targets. In this review article, we will go through current potential treatments for optic nerve regeneration, which includes neurotrophic factor provision, inflammatory stimulation, growth inhibition suppression, intracellular signaling modification and modeling of bridging substrates. PMID:26981073

  11. [Neuropathic pain intensity depends on the degree of peripheral nerve injury in the rat].

    PubMed

    Abuduhadeer, Tayier

    2004-12-01

    Partial peripheral nerve injury produces a persistent neuropathic pain which is difficult to relieve. In order to determine whether different degrees of peripheral nerve injury are related with the severity of neuropathic pain, we examined pain-related behaviors, histological changes and NGF in the skin in rats treated with different types of spinal nerve injury: tight ligation of the left L5 spinal nerve, incomplete ligation of the left L4 and L5 spinal nerves and incomplete crush of the left L4 and L5 spinal nerves. In all model rats, the thresholds of paw withdrawal in response to mechanical and heat stimuli began to decrease on the injured side 1 day after the operation, and the decreases in the thresholds persisted for more than 1 month. Incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves caused more severe allodynia and hyperalgesia than tight ligation of the left L5 spinal nerve on the injured side. In rats treated with incomplete crush, the threshold of withdrawal response to mechanical or heat stimuli was improved on day 32 after the operation as compared with that on day 15. Histological analysis revealed that about 80% of the fibers in the sciatic nerve were injured after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves on day 15, while about 50% of the fibers were damaged by tight ligation of the left L5 spinal nerve. In accordance with pain-relieving, the sciatic nerve fibers regenerated to about 50% of the number of the intact sciatic nerve fibers on day 32 in the crush model. Nerve growth factor (NGF) in the skin of the hindpaw on the injured side was accumulated after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves, but not tight ligation of the left L5 spinal nerve, on day 15 after the operation, possibly due to impairment of transport via unmyelinated primary afferents. Regeneration of the sciatic nerve alleviated the accumulation of NGF in the injured side hindpaw

  12. Surface Morphological Studies on Nerve Cells by AFM

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

    Surface morphological properties of fixed and living nerve cells removed from the buccal ganglion of Helisoma trivolvis have been studied by using Atomic Force Microscopy (AFM). Identified, individual neurons were removed from the buccal ganglion of Helisoma trivolvis and plated into poly-L-lysine coated glass cover-slips. The growth of the nerve cells was stopped and fixed with 0.1% Glutaraldehyde and 4% Formaldehyde solution after extension of growth cones at the tip of the axons. Topography and softness of growth cone filopodia and overlying lamellopodium (veil) were probed by AFM. Information obtained from AFM's amplitude and phase channels have been used for determination of softness of the region probed. The results of structural studies on the cells are linked to their mechanical properties and internal molecular density distribution.

  13. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia.

    PubMed

    Li, Qinwen; Chen, Jianghai; Chen, Yanhua; Cong, Xiaobin; Chen, Zhenbing

    2016-03-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription‑quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post‑compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR‑labeled DRG neurons were significantly higher, relative to the sham‑operated group, however, the numbers of FG‑labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor‑β1 (TGF‑β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)‑extracellular signal‑regulated kinase 1/2, and significantly lower levels of p‑c‑Jun N‑terminal kinase and p‑p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF‑β1, CTGF and collagen type I, with involvement of the mitogen‑activated protein kinase signaling pathway. PMID:26820076

  14. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia

    PubMed Central

    LI, QINWEN; CHEN, JIANGHAI; CHEN, YANHUA; CONG, XIAOBIN; CHEN, ZHENBING

    2016-01-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post-compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR-labeled DRG neurons were significantly higher, relative to the sham-operated group, however, the numbers of FG-labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)-extracellular signal-regulated kinase 1/2, and significantly lower levels of p-c-Jun N-terminal kinase and p-p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF-β1, CTGF and collagen type I, with involvement of the mitogen-activated protein kinase signaling pathway. PMID:26820076

  15. Human periodontal ligament stem cells repair mental nerve injury

    PubMed Central

    Li, Bohan; Jung, Hun-Jong; Kim, Soung-Min; Kim, Myung-Jin; Jahng, Jeong Won; Lee, Jong-Ho

    2013-01-01

    Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells (1 × 106) were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells (1 × 106) and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was significantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after injection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury. PMID:25206604

  16. Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

    PubMed

    Murayama, M; Sasaki, K; Shibahara, T

    2015-12-01

    The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration. PMID:26433750

  17. From nerve net to nerve ring, nerve cord and brain--evolution of the nervous system.

    PubMed

    Arendt, Detlev; Tosches, Maria Antonietta; Marlow, Heather

    2016-01-01

    The puzzle of how complex nervous systems emerged remains unsolved. Comparative studies of neurodevelopment in cnidarians and bilaterians suggest that this process began with distinct integration centres that evolved on opposite ends of an initial nerve net. The 'apical nervous system' controlled general body physiology, and the 'blastoporal nervous system' coordinated feeding movements and locomotion. We propose that expansion, integration and fusion of these centres gave rise to the bilaterian nerve cord and brain. PMID:26675821

  18. Cranial Nerves IX, X, XI, and XII

    PubMed Central

    Sanders, Richard D.

    2010-01-01

    This article concludes the series on cranial nerves, with review of the final four (IX–XII). To summarize briefly, the most important and common syndrome caused by a disorder of the glossopharyngeal nerve (craniel nerve IX) is glossopharyngeal neuralgia. Also, swallowing function occasionally is compromised in a rare but disabling form of tardive dyskinesia called tardive dystonia, because the upper motor portion of the glossopharyngel nerve projects to the basal ganglia and can be affected by lesions in the basal ganglia. Vagus nerve funtion (craniel nerve X) can be compromised in schizophrenia, bulimia, obesity, and major depression. A cervical lesion to the nerve roots of the spinal accessory nerve (craniel nerve XI) can cause a cervical dystonia, which sometimes is misdiagnosed as a dyskinesia related to neuroleptic use. Finally, unilateral hypoglossal (craniel nerve XII) nerve palsy is one of the most common mononeuropathies caused by brain metastases. Supranuclear lesions of cranial nerve XII are involved in pseudobulbar palsy and ALS, and lower motor neuron lesions of cranial nerve XII can also be present in bulbar palsy and in ALS patients who also have lower motor neuron involvement. This article reviews these and other syndromes related to cranial nerves IX through XII that might be seen by psychiatry. PMID:20532157

  19. What Protects Certain Nerves from Stretch Injury?

    PubMed

    Schraut, Nicholas B; Walton, Sharon; Bou Monsef, Jad; Shott, Susan; Serici, Anthony; Soulii, Lioubov; Amirouche, Farid; Gonzalez, Mark H; Kerns, James M

    2016-01-01

    The human tibial nerves is less prone to injury following joint arthroplasty compared with the peroneal nerves. Besides the anatomical distribution, other features may confer protection from stretch injury. We therefore examined the size, shape and connective tissue distribution for the two nerves. The tibial and peroneal nerves from each side of nine fresh human cadavers we reharvested mid-thigh. Proximal segments manually stretched 20%-25% were fixed in aldehyde, while the adjacent distal segments were fixed in their natural length. Paraffin sections stained by Masson's trichrome method for connective tissue were examined by light microscopy. Tibial nerves had 2X more fascicles compared with the peroneal, but the axonal content appeared similar. Analysis showed that neither nerve had a significant reduction in cross sectional area of the fascicles following stretch. However, fascicles from stretched tibial nerves become significantly more oval compared with those from unstretched controls and peroneal nerves. Tibial nerves had a greater proportion that was extrafascicular tissue (50-55%) compared with peroneal nerves (38%-42%). This epineurium was typically adipose tissue. Perineurial thickness in both nerves was directly related to fascicular size. Tibial nerves have several unique histological features associated with size, shape and tissue composition compared with the peroneal nerve. We suggest that more fascicles with their tightly bound perineurium and more robust epineurium afford protection against stretch injury. Mechanical studies should clarify how size and shape contribute to nerve protection and/or neurapraxia. PMID:26529568

  20. Inhalational exposure to nerve agents.

    PubMed

    Niven, Alexander S; Roop, Stuart A

    2004-03-01

    The respiratory system plays a major role in the pathogenesis of nerve agent toxicity. It is the major route of entry and absorption of nerve agent vapor, and respiratory failure is the most common cause of death follow-ing exposure. Respiratory symptoms are mediated by chemical irritation,muscarinic and nicotinic receptor overstimulation, and central nervous system effects. Recent attacks have demonstrated that most patients with an isolated vapor exposure developed respiratory symptoms almost immediately. Most patients had only mild and transient respiratory effects, and those that did develop significant respiratory compromise did so rapidly. These observations have significant ramifications on triage of patients in a mass-casualty situation, because patients with mild-to-moderate exposure to nerve agent vapor alone do not require decontamination and are less likely to develop progressive symptoms following initial antidote therapy. Limited data do not demonstrate significant long-term respiratory effects following nerve agent exposure and treatment. Provisions for effective respiratory protection against nerve agents is a vital consideration in any emergency preparedness or health care response plan against a chemical attack. PMID:15062227

  1. Rehabilitation of the trigeminal nerve

    PubMed Central

    Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank

    2005-01-01

    When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts. In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID:22073060

  2. Facial-hypoglossal nerve anastomosis using laser nerve welding.

    PubMed

    Hwang, Kun; Kim, Sun Goo; Kim, Dae Joong

    2006-07-01

    The aim of this study is to compare laser nerve welding to microsurgical suturing of hypoglossal-facial nerve anastomosis (HFA), and a result of immediate to delayed repair, and to evaluate the effect of laser nerve welding on HFA for reanimation of facial palsy. The first group of five rats underwent immediate HFA by microsurgical suturing and the second group of five rats by CO2 laser welding. The third group of five rats underwent delayed HFA by microsurgical suturing, and the fourth group of five rats by laser nerve welding. The fifth group of five rats served as controls, with intact hypoglossal and facial nerve. In all rats of the four different treatment groups, cholera toxin B subunit (CTb) was injected in the epineurium distal to the anastomosis site on the postoperative 6th week and in the normal hypoglossal nerve in the five rats of the control group. Neurons labeled CTb of hypoglossal nuclei were positive immunohistochemically, and the numbers were counted. In the immediate HFA groups, CTb-positive neurons were 751 +/- 247 in the laser welding group (n = 5) and 888 +/- 60 in the microsurgical suturing group (n = 5). There was no significant difference (P = 0.117). In the delayed HFA groups, CTb-positive neurons were 749 +/- 54 in the laser welding group (n = 5) and 590 +/- 169 in the microsurgical suturing group (n = 5). The difference was not significant (P = 0.116). There was no significant difference between immediate and delayed anastomosis in the laser welding group (P = 0.600), but there was significance between immediate and delayed anastomosis in the microsurgical suturing group (P = 0.009). Injected CTb in intact hypoglossal neurons (n = 5) were labeled 1,003 +/- 52. No dehiscence in the laser welding site of nerve anastomosis was seen at the time of re-exploration for injection of CTb in all 10 rats. This study shows that the regeneration of anastomosed hypoglossal-facial nerve was affected similarly by laser welding and microsurgical suturing

  3. Fractionated Stereotactic Radiotherapy for Facial Nerve Schwannomas.

    PubMed

    Shi, Wenyin; Jain, Varsha; Kim, Hyun; Champ, Colin; Jain, Gaurav; Farrell, Christopher; Andrews, David W; Judy, Kevin; Liu, Haisong; Artz, Gregory; Werner-Wasik, Maria; Evans, James J

    2016-02-01

    Purpose Data on the clinical course of irradiated facial nerve schwannomas (FNS) are lacking. We evaluated fractionated stereotactic radiotherapy (FSRT) for FNS. Methods Eight consecutive patients with FNS treated at our institution between 1998 and 2011 were included. Patients were treated with FSRT to a median dose of 50.4 Gy (range: 46.8-54 Gy) in 1.8 or 2.0 Gy fractions. We report the radiographic response, symptom control, and toxicity associated with FSRT for FNS. Results The median follow-up time was 43 months (range: 10-75 months). All patients presented with symptoms including pain, tinnitus, facial asymmetry, diplopia, and hearing loss. The median tumor volume was 1.57 cc. On the most recent follow-up imaging, five patients were noted to have stable tumor size; three patients had a net reduction in tumor volume. Additionally, six patients had improvement in clinical symptoms, one patient had stable clinical findings, and one patient had worsened House-Brackmann grade due to cystic degeneration. Conclusion FSRT treatment of FNS results in excellent control of growth and symptoms with a small rate of radiation toxicity. Given the importance of maintaining facial nerve function, FSRT could be considered as a primary management modality for enlarging or symptomatic FNS. PMID:26949592

  4. A precision mechanical nerve stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1988-01-01

    An electromechanical device, used to apply and monitor stimulating pulses to a mammalian motor nerve, has been successfully developed at NASA Langley Research Center. Two existing force transducers, a flight skin friction balance and a miniature skin friction balance which were designed for making aerodynamic drag measurements, were modified and incorporated to form this precision instrument. The nerve stimulator is a type one servomechanism capable of applying and monitoring stimulating pulses of 0 to 10 grams with a precision of better than +/- 0.05 grams. Additionally, the device can be independently used to apply stimulating pulses by displacing the nerve from 0 to 0.25 mm with a precision of better than +/- 0.001 mm while measuring the level of the load applied.

  5. [Paraganglioma of the vagus nerve].

    PubMed

    Torres-Carranza, E; Infante-Cossío, P; García-Perla, A; Belmonte, R; Menéndez, J; Gutiérrez-Pérez, J L

    2006-06-01

    Paragangliomas of the vagus nerve are uncommon vascular benign neoplasms of neuroectodermic origin. Initial clinical manifestation is usually as an asymptomatic cervical mass, although sometimes may cause lower cranial nerve palsies. These paragangliomas seldom associate to high levels of circulating catecholamines. Diagnosis is based on the clinics aided by imaging, where CT and MRI play an important role. Angiography is not only diagnostic, but it also allows preoperative embolization of the mass. Most accepted treatment is surgical removal, even though some paragangliomas are suitable for radiation therapy in very specific patients. In this paper we describe a new case of paraganglioma of the vagus nerve in a cervical location, with hypertensive episodes and high catecholamine-levels. The authors review the literature describing the clinical presentation, the diagnosis and the treatment of this rare lesion. PMID:16855784

  6. Facial nerve paralysis in children

    PubMed Central

    Ciorba, Andrea; Corazzi, Virginia; Conz, Veronica; Bianchini, Chiara; Aimoni, Claudia

    2015-01-01

    Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology. PMID:26677445

  7. Facial nerve paralysis in children.

    PubMed

    Ciorba, Andrea; Corazzi, Virginia; Conz, Veronica; Bianchini, Chiara; Aimoni, Claudia

    2015-12-16

    Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology. PMID:26677445

  8. Chemical warfare. Nerve agent poisoning.

    PubMed

    Holstege, C P; Kirk, M; Sidell, F R

    1997-10-01

    The threat of civilian and military casualties from nerve agent exposure has become a greater concern over the past decade. After rapidly assessing that a nerve agent attack has occurred, emphasis must be placed on decontamination and protection of both rescuers and medical personnel from exposure. The medical system can become rapidly overwhelmed and strong emotional reactions can confuse the clinical picture. Initially, care should first be focused on supportive care, with emphasis toward aggressive airway maintenance and decontamination. Atropine should be titrated, with the goal of therapy being drying of secretions and the resolution of bronchoconstriction and bradycardia. Early administration of pralidoxime chloride maximizes antidotal efficacy. Benzodiazepines, in addition to atropine, should be administered if seizures develop. Early, aggressive medical therapy is the key to prevention of the morbidity and mortality associated with nerve agent poisoning. PMID:9330846

  9. Initial formation and secondary condensation of nerve pathways in the medicinal leech.

    PubMed

    Jellies, J; Kopp, D M; Johansen, K M; Johansen, J

    1996-09-01

    Invertebrates have proved to be important experimental systems for examining questions related to growth cone navigation and nerve formation, in large part because of their simpler nervous systems. However, such apparent simplicity can be deceiving because the final stereotyped patterns may be the result of multiple developmental mechanisms and not necessarily the sole consequence of the pathway choices of individual growth cones. We have examined the normal sequence of events that are involved in the formation of the major peripheral nerves in leech embryos by employing (1) an antibody directed against acetylated tubulin to label neurons growing out from the central nervous system, (2) the Lan3-2 antibody to label a specific population of peripheral neurons growing into the central nervous system, and (3) intracellular dye filling of single cells. We found that the mature pattern of nerves was characterized by a pair of large nerve roots, each of which branched into two major tracts. The earliest axonal projections did not, however, establish this pattern definitively. Rather, each of the four nerves initially formed as discrete, roughly parallel tracts without bifurcation, with the final branching pattern of the nerve roots being generated by a secondary condensation. In addition, we found that some of the nerves were pioneered in different ways and by different groups of neurons. One of the nerves was established by central neurons growing peripherally, another by peripheral neurons growing centrally. These results suggest that the formation of common nerves and neuronal pathfinding in the leech involves multiple sets of growth cone guidance strategies and morphogenetic mechanisms that belie its apparent simplicity. PMID:8876458

  10. Peripheral nerve disease in pregnancy.

    PubMed

    Klein, Autumn

    2013-06-01

    Neuropathies during pregnancy and the postpartum period are common and are usually due to compression around pregnancy and childbirth. The most common peripheral neuropathies are Bell's palsy, carpal tunnel syndrome (CTS), and lower extremity neuropathies. Although most neuropathies are usually reversible, associated disabilities or morbidities can limit functioning and require therapy. Nerve conduction study tests and imaging should only be considered if symptoms are unusual or prolonged. Some neuropathies may be associated with preeclampsia or an inherent underlying neuropathy that increases the risk of nerve injury. All neuropathies in pregnancy should be followed as some may be persistent and require follow-up. PMID:23563878

  11. Nerve lesioning with direct current

    NASA Astrophysics Data System (ADS)

    Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

    2011-02-01

    Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

  12. Fabrication and characterization of biomimetic multichanneled crosslinked-urethane doped polyester (CUPE) tissue engineered nerve guides

    PubMed Central

    Tran, Richard. T.; Choy, Wai Man; Cao, Hung; Qattan, Ibrahim; Chiao, Jung-Chih; Ip, Wing Yuk; Yeung, Kelvin Wai Kwok; Yang, Jian

    2013-01-01

    Biomimetic scaffolds that replicate the native architecture and mechanical properties of target tissues have been recently shown to be a very promising strategy to guide cellular growth and facilitate tissue regeneration. In this study, porous, soft, and elastic crosslinked urethane-doped polyester (CUPE) tissue engineered nerve guides were fabricated with multiple longitudinally oriented channels and an external non-porous sheath to mimic the native endoneurial microtubular and epineurium structure, respectively. The fabrication technique described herein is highly adaptable and allows for fine control over the resulting nerve guide architecture in terms of channel number, channel diameter, porosity, and mechanical properties. Biomimetic multichanneled CUPE guides were fabricated with various channel numbers and displayed an ultimate peak stress of 1.38 ± 0.22 MPa with a corresponding elongation at break of 122.76 ± 42.17 %, which were comparable to that of native nerve tissue. The CUPE nerve guides were also evaluated in vivo for the repair of a 1 cm rat sciatic nerve defect. Although histological evaluations revealed collapse of the inner structure from CUPE TENGs, the CUPE nerve guides displayed fiber populations and densities comparable with nerve autograft controls after 8 weeks of implantation. These studies are the first report of a CUPE-based biomimetic multichanneled nerve guide and warrant future studies towards optimization of the channel geometry for use in neural tissue engineering. PMID:24115502

  13. In vivo study of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration

    NASA Astrophysics Data System (ADS)

    Koh, H. S.; Yong, T.; Teo, W. E.; Chan, C. K.; Puhaindran, M. E.; Tan, T. C.; Lim, A.; Lim, B. H.; Ramakrishna, S.

    2010-08-01

    A novel nanofibrous construct for promoting peripheral nerve repair was fabricated and tested in a rat sciatic nerve defect model. The conduit is made out of bilayered nanofibrous membranes with the nanofibers longitudinally aligned in the lumen and randomly oriented on the outer surface. The intra-luminal guidance channel is made out of aligned nanofibrous yarns. In addition, biomolecules such as laminin and nerve growth factor were incorporated in the nanofibrous nerve construct to determine their efficacy in in vivo nerve regeneration. Muscle reinnervation, withdrawal reflex latency, histological, axon density and electrophysiology tests were carried out to compare the efficacy of nanofibrous constructs with an autograft. Our study showed mixed results when comparing the artificial constructs with an autograft. In some cases, the nanofibrous conduit with aligned nanofibrous yarn as an intra-luminal guidance channel performs better than the autograft in muscle reinnervation and withdrawal reflex latency tests. However, the axon density count is highest in the autograft at mid-graft. Functional recovery was improved with the use of the nerve construct which suggested that this nerve implant has the potential for clinical usage in reconstructing peripheral nerve defects.

  14. PRGD/PDLLA conduit potentiates rat sciatic nerve regeneration and the underlying molecular mechanism.

    PubMed

    Li, Binbin; Qiu, Tong; Iyer, K Swaminathan; Yan, Qiongjiao; Yin, Yixia; Xie, Lijuan; Wang, Xinyu; Li, Shipu

    2015-07-01

    Peripheral nerve injury requires optimal conditions in both macro-environment and micro-environment for reestablishment. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the micro-environment provided by nerve conduit remains unclear. In this study, the rat sciatic nerve of 10 mm defect was made and bridged by PRGD/PDLLA nerve conduit. We investigated the process of nerve regeneration using histological, functional and real time PCR analyses after implantation from 7 to 35 days. Our data demonstrated that the ciliary neurotrophic factor highly expressed and up-regulated the downstream signaling pathways, in the case of activated signals, the expressions of axon sprout relative proteins, such as tubulin and growth-associated protein-43, were strongly augmented. Taken together, these data suggest a possible mechanism of axon regeneration promoted by PRGD/PDLLA conduit, which created a micro-environment for enhancement of diffusion of neurotrophic factors secreted by the injured nerve stumps, and activation of molecular signal transduction involved in growth cone, to potentiate the nerve recovery. PMID:25934451

  15. Nerve supply to the pelvis (image)

    MedlinePlus

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

  16. Infraspinatus muscle atrophy from suprascapular nerve compression.

    PubMed

    Cordova, Christopher B; Owens, Brett D

    2014-02-01

    Muscle weakness without pain may signal a nerve compression injury. Because these injuries should be identified and treated early to prevent permanent muscle weakness and atrophy, providers should consider suprascapular nerve compression in patients with shoulder muscle weakness. PMID:24463748

  17. Peripheral nerve regeneration through a silicone chamber implanted with negative carbon ions: Possibility to clinical application

    NASA Astrophysics Data System (ADS)

    Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Tsuji, Hiroshi; Yasuda, Tadashi; Matsuda, Shuichi

    2014-08-01

    We investigated whether a tube with its inner surface implanted with negative-charged carbon ions (C- ions) would enable axons to extend over a distance greater than 10 mm. The tube was found to support nerves regenerating across a 15-mm-long inter-stump gap. We also investigated whether a C- ion-implanted tube pretreated with basic fibroblast growth factor (bFGF) promotes peripheral nerve regeneration. The C- ion implanted tube accelerated nerve regeneration, and this effect was enhanced by bFGF. Silicone treated with C- ions showed increased hydrophilic properties and cellular affinity, and axon regeneration was promoted with this increased biocompatibility.

  18. Proximal Sciatic Nerve Intraneural Ganglion Cyst

    PubMed Central

    Swartz, Karin R.; Wilson, Dianne; Boland, Michael; Fee, Dominic B.

    2009-01-01

    Intraneural ganglion cysts are nonneoplastic, mucinous cysts within the epineurium of peripheral nerves which usually involve the peroneal nerve at the knee. A 37-year-old female presented with progressive left buttock and posterior thigh pain. Magnetic resonance imaging revealed a sciatic nerve mass at the sacral notch which was subsequently revealed to be an intraneural ganglion cyst. An intraneural ganglion cyst confined to the proximal sciatic nerve has only been reported once prior to 2009. PMID:20069041

  19. Patterned substrates and methods for nerve regeneration

    DOEpatents

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

    2004-01-13

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

  20. Effect of Artificial Nerve Conduit Vascularization on Peripheral Nerve in a Necrotic Bed

    PubMed Central

    Iijima, Yuki; Murayama, Akira; Takeshita, Katsushi

    2016-01-01

    Background: Several types of artificial nerve conduit have been used for bridging peripheral nerve gaps as an alternative to autologous nerves. However, their efficacy in repairing nerve injuries accompanied by surrounding tissue damage remains unclear. We fabricated a novel nerve conduit vascularized by superficial inferior epigastric (SIE) vessels and evaluated whether it could promote axonal regeneration in a necrotic bed. Methods: A 15-mm nerve conduit was implanted beneath the SIE vessels in the groin of a rat to supply it with blood vessels 2 weeks before nerve reconstruction. We removed a 13-mm segment of the sciatic nerve and then pressed a heated iron against the dorsal thigh muscle to produce a burn. The defects were immediately repaired with an autograft (n = 10), nerve conduit graft (n = 8), or vascularized nerve conduit graft (n = 8). Recovery of motor function was examined for 18 weeks after surgery. The regenerated nerves were electrophysiologically and histologically evaluated. Results: The vascularity of the nerve conduit implanted beneath the SIE vessels was confirmed histologically 2 weeks after implantation. Between 14 and 18 weeks after surgery, motor function of the vascularized conduit group was significantly better than that of the nonvascularized conduit group. Electrophysiological and histological evaluations revealed that although the improvement did not reach the level of reinnervation achieved by an autograft, the vascularized nerve conduit improved axonal regeneration more than did the conduit alone. Conclusion: Vascularization of artificial nerve conduits accelerated peripheral nerve regeneration, but further research is required to improve the quality of nerve regeneration. PMID:27257595

  1. Intact subepidermal nerve fibers mediate mechanical hypersensitivity via the activation of protein kinase C gamma in spared nerve injury

    PubMed Central

    Ko, Miau-Hwa; Yang, Ming-Ling; Youn, Su-Chung; Tseng, To-Jung

    2016-01-01

    Background Spared nerve injury is an important neuropathic pain model for investigating the role of intact primary afferents in the skin on pain hypersensitivity. However, potential cellular mechanisms remain poorly understood. In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization. The downstream cascades of PDK1 include: (1) protein kinase C gamma (PKCγ) controls the trafficking and phosphorylation of ionotropic glutamate receptor; (2) protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) signaling is responsible for local protein synthesis. Under these statements, we therefore hypothesized that an increase of PKCγ activation and mTOR-dependent PKCγ synthesis in intact primary afferents after SNI might contribute to pain hypersensitivity. Results The variants of spared nerve injury were performed in Sprague-Dawley rats by transecting any two of the three branches of the sciatic nerve, leaving only one branch intact. Following SNIt (spared tibial branch), mechanical hyperalgesia and mechanical allodynia, but not thermal hyperalgesia, were significantly induced. In the first footpad, normal epidermal innervations were verified by the protein gene product 9.5 (PGP9.5)- and growth-associated protein 43 (GAP43)-immunoreactive (IR) intraepidermal nerve fibers (IENFs) densities. Furthermore, the rapid increases of phospho-PKCγ- and phospho-mTOR-IR subepidermal nerve fibers (SENFs) areas were distinct gathered from the results of PGP9.5-, GAP43-, and neurofilament 200 (NF200)-IR SENFs areas. The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Conclusions From results obtained in this study, we strongly recommend that the intact SENFs persistently increase PKCγ activation and mTOR-dependent PKCγ synthesis participate

  2. Benign Nerve Sheath Myxoma in an Infant Misdiagnosed as Infantile Digital Fibromatosis.

    PubMed

    Güngör, Şule; Şişman, Servet; Kocaturk, Emek; Oguz Topal, Ilteris; Yıldırım, Selda

    2016-07-01

    Herein we present the case of a 16-month boy, clinically diagnosed with infantile digital fibromatosis, but 9 months after continued growth, the mass was excised and the histopathologic diagnosis was that of a benign nerve sheath myxoma. We present this case to emphasize that nerve sheath myxomas (also known as myxoid neurothekeoma) should be included in the differential diagnosis of dermal nodules in infants. PMID:27196676

  3. Changes induced by peripheral nerve injury in the morphology and nanomechanics of sensory neurons

    NASA Astrophysics Data System (ADS)

    Benzina, Ouafa; Szabo, Vivien; Lucas, Olivier; Saab, Marie-belle; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla; Martin, Marta

    2013-06-01

    Peripheral nerve injury in vivo promotes a regenerative growth in vitro characterized by an improved neurite regrowth. Knowledge of the conditioning injury effects on both morphology and mechanical properties of live sensory neurons could be instrumental to understand the cellular and molecular mechanisms leading to this regenerative growth. In the present study, we use differential interference contrast microscopy, fluorescence microscopy and atomic force microscopy (AFM) to show that conditioned axotomy, induced by sciatic nerve injury, does not increase somatic size of sensory neurons from adult mice lumbar dorsal root ganglia but promotes the appearance of longer and larger neurites and growth cones. AFM on live neurons is also employed to investigate changes in morphology and membrane mechanical properties of somas of conditioned neurons following sciatic nerve injury. Mechanical analysis of the soma allows distinguishing neurons having a regenerative growth from control ones, although they show similar shapes and sizes.

  4. Neurophysiologic intraoperative monitoring: II. Facial nerve function.

    PubMed

    Niparko, J K; Kileny, P R; Kemink, J L; Lee, H M; Graham, M D

    1989-01-01

    Intraoperative facial nerve monitoring provides a potentially useful adjunct to recent surgical advances in neurotology and neurosurgery. These measures further aid the surgeon in preserving facial nerve function by enhancing visual identification with electrical monitoring of mechanically evoked facial muscle activation. Facial nerve monitoring in neurotologic surgery may achieve the following goals: (1) early recognition of surgical trauma to the facial nerve, with immediate feedback made available to the surgeon through monitoring of mechanical activation; (2) assistance in distinguishing the facial nerve from regional cranial nerves and from adjacent soft tissue and tumor with selective electrical stimulation; (3) facilitation of tumor excision by electrical mapping of portions of tumor that are remote from the facial nerve; (4) confirmation of nerve stimulability at the completion of surgery; and (5) identification of the site and degree of neural dysfunction in patients undergoing nerve exploration for suspected facial nerve neoplasm or undergoing decompression in acute facial palsy. This paper provides an overview of intraoperative facial nerve monitoring principles and methodology and reports a recent clinical investigation that demonstrates the utility of facial nerve monitoring in translabyrinthine acoustic neuroma surgery. PMID:2655465

  5. Endoscopic-assisted infraorbital nerve release

    PubMed Central

    Sosin, Michael; De La Cruz, Carla; Christy, Michael R.

    2014-01-01

    Abstract Endoscopic-assisted techniques in plastic and craniofacial surgeries are limited. We present a patient with infraorbital nerve entrapment following traumatic facial injury that failed conservative management. Compression of the nerve was treated with an endoscopic-assisted nerve release of the surrounding soft tissue with a circumferential foraminal osteotomy.

  6. Facial nerve palsy due to birth trauma

    MedlinePlus

    Seventh cranial nerve palsy due to birth trauma ... these factors do not lead to facial nerve palsy or birth trauma. ... The most common form of facial nerve palsy due to birth trauma ... This part controls the muscles around the lips. The muscle ...

  7. 21 CFR 882.5275 - Nerve cuff.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nerve cuff. 882.5275 Section 882.5275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5275 Nerve cuff. (a) Identification. A nerve...

  8. 21 CFR 882.5275 - Nerve cuff.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nerve cuff. 882.5275 Section 882.5275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5275 Nerve cuff. (a) Identification. A nerve...

  9. 21 CFR 882.5275 - Nerve cuff.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nerve cuff. 882.5275 Section 882.5275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5275 Nerve cuff. (a) Identification. A nerve...

  10. 21 CFR 882.5275 - Nerve cuff.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nerve cuff. 882.5275 Section 882.5275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5275 Nerve cuff. (a) Identification. A nerve...

  11. 21 CFR 882.5275 - Nerve cuff.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nerve cuff. 882.5275 Section 882.5275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5275 Nerve cuff. (a) Identification. A nerve...

  12. Neurofibrosarcoma of the vagus nerve

    PubMed Central

    Corris, P. A.

    1983-01-01

    A patient whose symptoms of cough and intermittent hoarseness were due to a neurofibrosarcoma of the vagus nerve is described. Attention is drawn to the rarity of the tumour and a short review of the pathology and treatment of neurofibrosarcoma is discussed. ImagesFig. 1 PMID:6844194

  13. Overview of Optic Nerve Disorders

    MedlinePlus

    ... pathways to the brain results in loss of vision. At a structure in the brain called the optic chiasm, each optic nerve splits, ... both eyes, and the left side of the brain receives information from the right visual field of both eyes. ... occurs. Resources ...

  14. Cranial nerve palsies in childhood

    PubMed Central

    Lyons, C J; Godoy, F; ALQahtani, E

    2015-01-01

    We review ocular motor cranial nerve palsies in childhood and highlight many of the features that differentiate these from their occurrence in adulthood. The clinical characteristics of cranial nerve palsies in childhood are affected by the child's impressive ability to repair and regenerate after injury. Thus, aberrant regeneration is very common after congenital III palsy; Duane syndrome, the result of early repair after congenital VI palsy, is invariably associated with retraction of the globe in adduction related to the innervation of the lateral rectus by the III nerve causing co-contraction in adduction. Clinical features that may be of concern in adulthood may not be relevant in childhood; whereas the presence of mydriasis in III palsy suggests a compressive aetiology in adults, this is not the case in children. However, the frequency of associated CNS abnormalities in III palsy and the risk of tumour in VI palsy can be indications for early neuroimaging depending on presenting features elicited through a careful history and clinical examination. The latter should include the neighbouring cranial nerves. We discuss the impact of our evolving knowledge of congenital cranial dysinnervation syndromes on this field. PMID:25572578

  15. The Diagnostic Value of Nerve Ultrasound in an Atypical Palmar Cutaneous Nerve Lesion.

    PubMed

    Zanette, Giampietro; Tamburin, Stefano

    2016-07-01

    Detailed knowledge of the fascicular anatomy of peripheral nerves is important for microsurgical repair and functional electrostimulation.We report a patient with a lesion on the left palmar cutaneous branch of the median nerve (PCBMN) and sensory signs expanding outside the PCBMN cutaneous innervation territory. Nerve conduction study showed the absence of left PCBMN sensory nerve action potential, but apparently, no median nerve (MN) involvement. Nerve ultrasound documented a neuroma of the left PCBMN and a coexistent lateral neuroma of the left MN in the carpal tunnel after the PCBMN left the main nerve trunk.Nerve ultrasound may offer important information in patients with peripheral nerve lesions and atypical clinical and/or nerve conduction study findings. The present case may shed some light on the somatotopy of MN fascicles at the wrist. PMID:26945219

  16. Nerve injury associated with orthognathic surgery. Part 1: UK practice and motor nerve injuries.

    PubMed

    Bowe, D C; Gruber, E A; McLeod, N M H

    2016-05-01

    The head and neck is anatomically complex, and several nerves are at risk during orthognathic operations. Some injuries to nerves are reported more commonly than others. To find out what consultant surgeons tell their patients about the prevalence of common nerve injuries before orthognathic operations, we did a postal survey of fellows of the British Association of Oral and Maxillofacial Surgeons (BAOMS). We also reviewed published papers to find out the reported incidence of injuries to cranial motor nerves during orthognathic operations. Only injuries to the facial nerve were commonly reported, and we found only case reports about injuries to the oculomotor, abducens, and trochlear nerves. The risk of temporary facial nerve palsy reported was 0.30/100 nerves (95% CI 0.23 to 0.50) and permanent facial nerve palsy was 0.06/100 nerves (95% CI 0.02 to 0.15). PMID:26935213

  17. Detection of peripheral nerve pathology

    PubMed Central

    Seelig, Michael J.; Baker, Jonathan C.; Mackinnon, Susan E.; Pestronk, Alan

    2013-01-01

    Objective: To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. Methods: We performed a retrospective review of patients referred for neuromuscular ultrasound to identify patients who had ultrasound and MRI of the same limb for suspected brachial plexopathy or mononeuropathies, excluding carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic evaluation. Results: We identified 53 patients who had both ultrasound and MRI of whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed nerve pathology (true positive) more often than MRI (43/46 vs 31/46, p < 0.001). Nerve pathology was correctly excluded (true negative) with equal frequency by MRI and ultrasound (both 6/7). In 25% (13/53), ultrasound was accurate (true positive or true negative) when MRI was not. These pathologies were typically (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view. MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients, often (5/7) because pathology was outside the MRI field of view. Conclusions: Imaging frequently detects peripheral nerve pathology and contributes to the differential diagnosis in patients with mononeuropathies and brachial plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions. PMID:23553474

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  19. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    PubMed Central

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  20. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair.

    PubMed

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-07-15

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  1. Morphological studies of the vestibular nerve

    NASA Technical Reports Server (NTRS)

    Bergstroem, B.

    1973-01-01

    The anatomy of the intratemporal part of the vestibular nerve in man, and the possible age related degenerative changes in the nerve were studied. The form and structure of the vestibular ganglion was studied with the light microscope. A numerical analysis of the vestibular nerve, and caliber spectra of the myelinated fibers in the vestibular nerve branches were studied in individuals of varying ages. It was found that the peripheral endings of the vestibular nerve form a complicated pattern inside the vestibular sensory epithelia. A detailed description of the sensory cells and their surface organelles is included.

  2. Nerve agents: implications for anesthesia providers.

    PubMed

    Hrobak, Paula Kay

    2008-04-01

    Anesthesia providers may be called to treat injuries from chemical weapons or spills, for which prompt treatment is vital. It is therefore important to understand the mechanism of action of nerve agents and the resultant pathophysiology and to be able to quickly recognize the signs and symptoms of nerve agent exposure. This review article addresses the different types of nerve agents that are currently being manufactured as well as the symptomatic and definitive treatment of the patient who presents with acute nerve agent toxicity. This article also reviews the physiology of the neuromuscular junction and the autonomic nervous system receptors that nerve agent toxicity affects. PMID:18478812

  3. Neuroplasticity of Sensory and Sympathetic Nerve Fibers in the Painful Arthritic Joint

    PubMed Central

    Ghilardi, Joseph R.; Freeman, Katie T.; Jimenez-Andrade, Juan M.; Coughlin, Kathleen; Kaczmarska, Magdalena J.; Castaneda-Corral, Gabriela; Bloom, Aaron P.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2012-01-01

    Objective Many forms of arthritis are accompanied by significant chronic joint pain. Here we studied whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathological reorganization. Methods A painful arthritic knee joint was produced by injection of complete Freund’s adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry using antibodies raised against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), growth associated protein-43 (GAP43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells) or CD68 (monocytes/macrophages). Results In CFA-injected mice, but not vehicle-injected mice, there was a significant increase in the density of CD68+ macrophages, CD31+ blood vessels, CGRP+, NF200+, GAP43+, and TH+ nerve fibers in the synovium as well as joint pain-related behaviors. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31+ blood vessels or CD68+ macrophages. Conclusions Ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain. PMID:22246649

  4. Electrical stimulation accelerates axonal and functional peripheral nerve regeneration across long gaps.

    PubMed

    Haastert-Talini, Kirsten; Schmitte, Ruth; Korte, Nele; Klode, Dorothee; Ratzka, Andreas; Grothe, Claudia

    2011-04-01

    Short-term low-frequency electrical stimulation (ESTIM) of proximal peripheral nerve stumps prior to end-to-end coaptation or tubular bridging of small distances has been reported to increase preferential motor reinnervation and functional motor recovery in animal models and human patients undergoing carpal tunnel release surgery. We investigated the effects of ESTIM on regeneration across rat sciatic nerve gaps, which exceed distances that allow spontaneous regeneration. Three different reconstruction approaches were combined with ESTIM in the experimental groups. Nerve gaps (13 mm) were bridged using (I) nerve autotransplantation, (II) transplantation of differentially filled silicone tubes, or (III) transplantation of tubular grafts containing fibroblast growth factor-2 overexpressing Schwann cells (SCs) for gene therapy. The regeneration outcome was followed for up to 8 weeks, and functionally as well as histomorphometrically analyzed in comparison to non-stimulated control groups. Combining ESTIM with nerve autotransplantation significantly increased the nerve fiber density in the regenerated nerve, and the grade of functional recovery as detected by electrodiagnostic recordings from the gastrocnemius muscle. The combination of ESTIM with transplantation of naïve SCs increased the regeneration of gap-bridging nerve tissue. Although macroscopic tissue regeneration was not further improved after combining ESTIM with FGF-2(21/23-kD) gene therapy, the latter resulted in a high rate of regenerated nerves that functionally reconnected to the target muscle. Based on our results, brief ESTIM shows high potential to accelerate axonal as well as functional (motor and sensory) outcomes in the clinical setting of peripheral nerve gap reconstruction in human patients. PMID:21265597

  5. Continuous peripheral nerve blocks in children.

    PubMed

    Dadure, C; Capdevila, X

    2005-06-01

    In recent years, regional anaesthesia in children has generated increasing interest. Continuous peripheral nerve blocks have an important role in the anaesthetic arsenal, allowing effective, safe and prolonged postoperative pain management. Indications for continuous peripheral nerve blocks depend on benefits/risks analysis of each technique for each patient. The indications include surgery associated with intense postoperative pain, surgery requiring painful physical therapy, and complex regional pain syndrome. Continuous peripheral nerve blocks are usually performed under general anaesthesia or sedation, and require appropriate equipment in order to decrease the risk of nerve injury. New techniques, such as transcutaneous stimulation or ultrasound guidance, appear to facilitate nerve and plexus identification in paediatric patients. Nevertheless, continuous peripheral nerve block may mask compartment syndrome in certain surgical procedure or trauma. Finally, ropivacaine appears to be the best local anaesthetic for continuous peripheral nerve blocks in children, requiring low flow rate with low concentration of the local anaesthetic. PMID:15966500

  6. Amniotic membrane covering for facial nerve repair☆

    PubMed Central

    Karaman, Murat; Tuncel, Arzu; Sheidaei, Shahrouz; Şenol, Mehmet Güney; Karabulut, Murat Hakan; Deveci, Ildem; Karaman, Nihan

    2013-01-01

    Amniotic membranes have been widely used in ophthalmology and skin injury repair because of their anti-inflammatory properties. In this study, we measured therapeutic efficacy and determined if amniotic membranes could be used for facial nerve repair. The facial nerves of eight rats were dissected and end-to-end anastomosis was performed. Amniotic membranes were covered on the anastomosis sites in four rats. Electromyography results showed that, at the end of the 3rd and 8th weeks after amniotic membrane covering, the latency values of the facial nerves covered by amniotic membranes were significantly shortened and the amplitude values were significantly increased. Compared with simple facial nerve anastomosis, after histopathological examination, facial nerve anastomosed with amniotic membrane showed better continuity, milder inflammatory reactions, and more satisfactory nerve conduction. These findings suggest that amniotic membrane covering has great potential in facial nerve repair. PMID:25206390

  7. Sensory nerve function and auto-mutilation after reconstruction of various gap lengths with nerve guides and autologous nerve grafts.

    PubMed

    den Dunnen, W F; Meek, M F

    2001-05-01

    The aim of this study was to evaluate sensory nerve recovery and auto-mutilation after reconstruction of various lengths of nerve gaps in the sciatic nerve of the rat, using different techniques. Group 4, in which the longest nerve gap (15 mm) was reconstructed with a thin-walled p(DL-lactide-gamma-caprolactone) nerve guide filled with modified denatured muscle tissue, showed the best results in the electro-stimulation tests and signs of severe auto-mutilation were not observed. Even in the control group, in which a 10 mm nerve gap was left open, in two of the five rats improvement of the sensory nerve function was observed, which was caused by re-innervation of the sciatic nerve and not by expansion of the neighboring saphenous nerve. It is hypothesized that a better quality of nerve reconstruction/guidance channel/support results in faster regeneration and hence re-innervation, thereby, preventing auto-mutilation. A thin red glabrous skin, anhydrosis (dryness of the skin), short nails and edema were interpreted as signs of autonomic dysfunction. PMID:11352096

  8. Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration

    PubMed Central

    Li, Guang-shuai; Li, Qing-feng; Dong, Ming-min; Zan, Tao; Ding, Shuang; Liu, Lin-bo

    2016-01-01

    Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8β and complement factor D) in the nerve regeneration conditioned fluid and each varied at different time points. These findings suggest that all these complement components have a functional role in nerve regeneration. PMID:27212935

  9. Evolution of peripheral nerve function in humans: novel insights from motor nerve excitability

    PubMed Central

    Farrar, Michelle A; Park, Susanna B; Lin, Cindy S-Y; Kiernan, Matthew C

    2013-01-01

    While substantial alterations in myelination and axonal growth have been described during maturation, their interactions with the configuration and activity of axonal membrane ion channels to achieve impulse conduction have not been fully elucidated. The present study utilized axonal excitability techniques to compare the changes in nerve function across healthy infants, children, adolescents and adults. Multiple excitability indices (stimulus–response curve, strength–duration time constant, threshold electrotonus, current–threshold relationship and recovery cycle) combined with conventional neurophysiological measures were investigated in 57 subjects (22 males, 35 females; age range 0.46–24 years), stimulating the median motor nerve at the wrist. Maturational changes in conduction velocity were paralleled by significant alterations in multiple excitability parameters, similarly reaching steady values in adolescence. Maturation was accompanied by reductions in threshold (P < 0.005) and rheobase (P= 0.001); depolarizing and hyperpolarizing electrotonus progressively reduced (P < 0.001), or ‘fanned-in’; resting current–threshold slope increased (P < 0.0001); accommodation to depolarizing currents prolonged (P < 0.0001); while greater threshold changes in refractoriness (P= 0.001) and subexcitability (P < 0.01) emerged. Taken together, the present findings suggest that passive membrane conductances and the activity of K+ conductances decrease with formation of the axo-glial junction and myelination. In turn, these functional alterations serve to enhance the efficiency and speed of impulse conduction concurrent with the acquisition of motor skills during childhood, and provide unique insight into the evolution of postnatal human peripheral nerve function. Significantly, these findings bring the dynamics of axonal development to the clinical domain and serve to further illuminate pathophysiological mechanisms that occur during development. PMID:23006483

  10. The longitudinal epineural incision and complete nerve transection method for modeling sciatic nerve injury

    PubMed Central

    Cheng, Xing-long; Wang, Pei; Sun, Bo; Liu, Shi-bo; Gao, Yun-feng; He, Xin-ze; Yu, Chang-yu

    2015-01-01

    Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery. PMID:26692866

  11. Effect of oblique nerve grafting on peripheral nerve regeneration in rats.

    PubMed

    Kotulska, Katarzyna; Marcol, Wiesław; Larysz-Brysz, Magdalena; Tendera, Zofia; Malinowska-Kołodziej, Izabela; Slusarczyk, Wojciech; Jedrzejowska-Szypułka, Halina; Lewin-Kowalik, Joanna

    2006-01-01

    Current methods of peripheral nerve repair are to rejoin cut nerve stumps directly or to bridge large gaps with autologous nerve grafts. In both cases the surface of nerve stump endings is typically cut perpendicularly to the long axis of the nerve. The outcome of such operations, however, is still not satisfactory. In this study, we examine the effect of oblique nerve cutting and grafting on morphological as well as functional features of regeneration. In adult rats, sciatic nerve was cut and rejoined either directly or using an autologous graft, at 90 degrees or 30 degrees angle. Functional regeneration was assessed by walking track analysis during 12-week follow-up. Afterwards muscle weight was measured and histological studies were performed. The latter included nerve fibers and Schwann cells counting, as well as visualization of scar formation and epineural fibrosis. Nerves cut obliquely and rejoined showed better functional recovery than perpendicularly transected. Similar effect was observed after oblique grafting when compared to perpendicular one. Numbers of nerve fibers growing into the distal stump of the nerve as well as the number of Schwann cells were significantly higher in obliquely than in perpendicularly operated nerves. Moreover, growing axons were arranged more regularly following oblique treatment. These data indicate that joining or grafting the nerve stumps at acute angle is a more profitable method of nerve repair than the standard procedure performed at right angle. PMID:17066410

  12. Nerve guidance channels as drug delivery vehicles.

    PubMed

    Piotrowicz, Alexandra; Shoichet, Molly S

    2006-03-01

    Nerve guidance channels (NGCs) have been shown to facilitate regeneration after transection injury to the peripheral nerve or spinal cord. Various therapeutic molecules, including neurotrophic factors, have improved regeneration and functional recovery after injury when combined with NGCs; however, their impact has not been maximized partly due to the lack of an appropriate drug delivery system. To address this limitation, nerve growth factor (NGF) was incorporated into NGCs of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate), P(HEMA-co-MMA). The NGCs were synthesized by a liquid-liquid centrifugal casting process and three different methods of protein incorporation were compared in terms of protein distribution and NGF release profile: (1) NGF was encapsulated (with BSA) in biodegradable poly(d,l-lactide-co-glycolide) 85/15 microspheres, which were combined with a PHEMA polymerization formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique; (2) pre-formed NGCs were imbibed with a solution of NGF/BSA and (3) NGF/BSA alone was combined with a PHEMA formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique. Using a fluorescently labelled model protein, the distribution of proteins in NGCs prepared with a coating of either protein-loaded microspheres or protein alone was found to be confined to the inner PHEMA layer. Sustained release of NGF was achieved from NGCs with either NGF-loaded microspheres or NGF alone incorporated into the inner layer, but not from channels imbibed with NGF. By day 28, NGCs with microspheres released a total of 220 pg NGF/cm of channel whereas those NGCs imbibed with NGF released 1040 pg/cm and those NGCs with NGF incorporated directly in a PHEMA layer released 8624 pg/cm. The release of NGF from NGCs with microspheres was limited by a slow-degrading microsphere formulation and by the maximum amount of microspheres that

  13. Alcohol neurolysis of digital nerves

    PubMed Central

    Wright, Garrett K.; Burnett, Christopher J.

    2016-01-01

    Alcohol neurolysis is a well-established treatment in chronic pain management, often used in cases of intractable cancer-related pain that is refractory to other management therapies. We describe a 76-year-old woman with chronic toe neuritis who failed multiple treatments, including oral and topical analgesics, nerve blocks, and radiofrequency ablations. Alcohol neurolysis was performed via digit block of the toe resulting in 100% pain relief. PMID:27365891

  14. Histological Study of Bone Marrow and Umbilical Cord Stromal Cell Transplantation in Regenerating Rat Peripheral Nerve

    PubMed Central

    Zarbakhsh, Sam; Goudarzi, Nasim; Shirmohammadi, Maryam; Safari, Manouchehr

    2016-01-01

    Objective Bone marrow and umbilical cord stromal cells are multipotential stem cells that have the ability to produce growth factors that play an important role in survival and generation of axons. The goal of this study was to evaluate the effects of the two different mesenchymal stem cells on peripheral nerve regeneration. Materials and Methods In this experimental study, a 10 mm segment of the left sciatic nerve of male Wistar rats (250-300 g) was removed with a silicone tube interposed into this nerve gap. Bone marrow stromal cells (BMSCs) and human umbilical cord stromal cells (HUCSCs) were respectively obtained from rat and human. The cells were sepa- rately cultured and transplanted into the nerve gap. The sciatic nerve regeneration was evaluated by immunohistochemistry, and light and electron microscopy. Moreover, histo- morphology of the gastrocnemius muscle was observed. Results The nerve regeneration in the BMSCs and HUCSCs groups that had received the stem cells was significantly more favorable than the control group. In addition, the BM- SCs group was significantly more favorable than the HUCSCs group (P<0.05). Conclusion The results of this study suggest that both homograft BMSCs and het- erograft HUCSCs may have the potential to regenerate peripheral nerve injury and transplantation of BMSCs may be more effective than HUCSCs in rat. PMID:26862526

  15. [Blood-nerve barrier: structure and function].

    PubMed

    Kanda, Takashi

    2011-06-01

    The blood-nerve barrier (BNB) is a dynamic interface between the endoneurial microenvironment and surrounding extracellular space or blood contents, and is localized the innermost layer of multilayered ensheathing perineurium and endoneurial microvessels. Since the BNB is a key structure controlling the internal milieu of the peripheral nerve parenchyma, adequate understanding of the BNB is crucial for developing treatment strategies for human peripheral nervous system disorders, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and diabetic and various metabolic/toxic neuropathies. However, fewer studies have been conducted on the BNB, if we compare against the number of studies on the blood-brain barrier. This is because of the lack of adequate human cell lines originating from the BNB. In our laboratory, human immortal cell lines from the BNB, namely, the endothelial cell line and pericyte cell line, have recently been established and vigorous investigations of their biological and physiological properties are now underway. Pericytes constituting the BNB were found to possess robust ability of controlling BNB integrity via secretion of various cytokines and growth factors including bFGF, VEGF, GDNF, BDNF, and angiopoietin-1. Unknown soluble factors secreted by pericytes also contribute to the upregulation of claudin-5 in endothelial cells in the BNB and thus, strengthen the barrier function of the BNB. In diabetic neuropathy, pericytes were shown to regulate the vascular basement membrane, while AGEs were shown to induce basement membrane hypertrophy and disrupt the BNB by increasing the autocrine secretion of VEGF and TGF-beta from pericytes. In this review article, we discuss the macroscopic and microscopic anatomy of the human BNB as well as the molecular mechanisms of mononuclear cell infiltration across the BNB. PMID:21613659

  16. Glaucoma and optic nerve repair.

    PubMed

    Diekmann, Heike; Fischer, Dietmar

    2013-08-01

    Glaucoma is a leading cause of irreversible blindness worldwide and causes progressive visual impairment attributable to the dysfunction and death of retinal ganglion cells (RGCs). Progression of visual field damage is slow and typically painless. Thus, glaucoma is often diagnosed after a substantial percentage of RGCs has been damaged. To date, clinical interventions are mainly restricted to the reduction of intraocular pressure (IOP), one of the major risk factors for this disease. However, the lowering of IOP is often insufficient to halt or reverse the progress of visual loss, underlining the need for the development of alternative treatment strategies. Several lines of evidence suggest that axonal damage of RGCs occurs primary at the optic nerve head, where axons appear to be most vulnerable. Axonal injury leads to the functional loss of RGCs and subsequently induces the death of the neurons. However, the detailed molecular mechanism(s) underlying IOP-induced optic nerve injury remain poorly understood. Moreover, whether glaucoma pathophysiology is primarily axonal, glial, or vascular remains unclear. Therefore, protective strategies to prevent further axonal and subsequent soma degeneration are of great importance to limit the progression of sight loss. In addition, strategies that stimulate injured RGCs to regenerate and reconnect axons with their central targets are necessary for functional restoration. The present review provides an overview of the context of glaucoma pathogenesis and surveys recent findings regarding potential strategies for axonal regeneration of RGCs and optic nerve repair, focusing on the role of cytokines and their downstream signaling pathways. PMID:23512141

  17. Bone Marrow-Derived, Neural-Like Cells Have the Characteristics of Neurons to Protect the Peripheral Nerve in Microenvironment

    PubMed Central

    Guo, Shi-lei; Zhang, Zhi-ying; Zhi, Yun-xia; Han, Chang-jie; Zhou, Yu-hao; Liu, Fang; Lin, Hai-yan; Zhang, Chuan-sen

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  19. Motor nerve conduction velocity (MCV) and lead content in sciatic nerve of lead-exposed rats

    SciTech Connect

    Maehara, N.; Uchino, E.; Terayama, K.; Ohno, H.; Yamamura, K.

    1986-07-01

    There have been many pathological and electrophysiological studies of peripheral nerves in inorganic lead intoxication. Peripheral nerve conduction velocity (NCV) has been used as an objective measure of the effects of lead on the peripheral nerve function and has been examined with blood lead content. There have been few reports on the changes in NCV related to lead content in the peripheral nerve tissue under lead poisoning. In the present study, the authors have examined motor nerve conduction velocity (MCV) of the tail by a non-invasive method and lead content of the peripheral nerve in lead-exposed rats. Furthermore, they have attempted to assess the relationship between these two parameters.

  20. Nerve hyperplasia: a unique feature of ketamine cystitis

    PubMed Central

    2013-01-01

    Background There is an emerging association between ketamine abuse and the development of urological symptoms including dysuria, frequency and urgency, which have a neurological component. In addition, extreme cases are associated with severe unresolving bladder pain in conjunction with a thickened, contracted bladder and an ulcerated/absent urothelium. Here we report on unusual neuropathological features seen by immunohistology in ketamine cystitis. Results In all cases, the lamina propria was replete with fine neurofilament protein (NFP+) nerve fibres and in most patients (20/21), there was prominent peripheral nerve fascicle hyperplasia that showed particular resemblance to Morton’s neuroma. The nerve fascicles, which were positive for NFP, S100 and the p75 low-affinity nerve growth factor receptor (NGFR), were generally associated with a well-developed and in places, prominent, epithelial membrane antigen+/NGFR+ perineurium. This peripheral nerve fascicle hyperplasia is likely to account for the extreme pain experienced by ketamine cystitis patients. Urothelial damage was a notable feature of all ketamine cystitis specimens and where urothelium remained, increased NGFR expression was observed, with expansion from a basal-restricted normal pattern of expression into the suprabasal urothelium. Conclusions The histological findings were distinguishing features of ketamine cystitis and were not present in other painful bladder conditions. Ketamine cystitis afflicts predominantly young patients, with unknown long-term consequences, and requires a strategy to control severe bladder pain in order to remove a dependency on the causative agent. Our study indicates that the development of pain in ketamine cystitis is mediated through a specific neurogenic mechanism that may also implicate the urothelium. PMID:24252413

  1. Mechanisms of nerve injury in leprosy.

    PubMed

    Scollard, David M; Truman, Richard W; Ebenezer, Gigi J

    2015-01-01

    All patients with leprosy have some degree of nerve involvement. Perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of Mycobacterium leprae into nerves. Once inside nerves, M. leprae are ingested by Schwann cells, with a wide array of consequences. Axonal atrophy may occur early in this process; ultimately, affected nerves undergo segmental demyelination. Knowledge of the mechanisms of nerve injury in leprosy has been greatly limited by the minimal opportunities to study affected nerves in man. The nine-banded armadillo provides the only animal model of the pathogenesis of M. leprae infection. New tools available for this model enable the study and correlation of events occurring in epidermal nerve fibers, dermal nerves, and nerve trunks, including neurophysiologic parameters, bacterial load, and changes in gene transcription in both neural and inflammatory cells. The armadillo model is likely to enhance understanding of the mechanisms of nerve injury in leprosy and offers a means of testing proposed interventions. PMID:25432810

  2. Ultrastructural observations on the progress of nerve degeneration and regeneration at the suture site following vagal-hypoglossal nerve coaptation in cats.

    PubMed

    Hu, Ming-E; Tyan, Yeu-Sheng; Hsu, Peng-Wei; Hsu, Jee-Ching; Chang, Hung-Ming; Ling, Eng-Ang; Lan, Chyn-Tair

    2009-01-01

    Nerve degeneration and regeneration have been investigated at the suture site following proximal-to-distal vagal-hypoglossal nerve coaptation (VHC) in cats at different time points (from 3 to 315 days postoperatively; dpo). Massive axonal degeneration and myelin breakdown and removal of degraded neural debris were observed during the first 2 weeks postoperatively. This was followed by active Schwann cell multiplication and inflammatory cell invasion at 14 dpo. Schwann cells appeared mobile, and were guided to the newly developed growth cones, dividing them into axonal sprout clusters. At 18 dpo, the migrating Schwann cells were confined to the preexisting basal lamina scaffolds, forming bands of Bungner. It is suggested that the latter may play a key role in navigating the regenerating axons to their newly acquired target organ at 22 dpo. Remyelination of axons was not observed till 46 dpo. Compared with the rapid axonal reaction in other models of nerve injury, the degeneration process in VHC was protracted and, furthermore, regeneration and remyelination were delayed. The subtle remodeling of the nerve in cross-coaptation may be far greater than previously recognized, and this may have clinical importance since patients undergoing nerve crossover microsurgery exhibit delayed motor rehabilitation, apparently as a direct result of a change in target innervation. Defining the mechanisms underlying the neuroplastic program could thus potentially improve the prognosis of crossover of two different peripheral nerves. PMID:19494480

  3. BREAST CANCER-INDUCED BONE REMODELING, SKELETAL PAIN AND SPROUTING OF SENSORY NERVE FIBERS

    PubMed Central

    Bloom, Aaron P.; Jimenez-Andrade, Juan M.; Taylor, Reid N.; Castañeda-Corral, Gabriela; Kaczmarska, Magdalena J.; Freeman, Katie T.; Coughlin, Kathleen A.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2011-01-01

    Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other non-malignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP+) sensory nerve fibers. Nearly all CGRP+ nerve fibers that undergo sprouting also co-express tropomyosin receptor kinase A (TrkA+) and growth associated protein-43 (GAP43+). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP+ / TrkA+ / GAP43+ sensory nerve fibers. PMID:21497141

  4. Blockade of Nerve Sprouting and Neuroma Formation Markedly Attenuates the Development of Late Stage Cancer Pain

    PubMed Central

    Mantyh, William G.; Jimenez-Andrade, Juan M.; Stake, James I.; Bloom, Aaron P.; Kaczmarska, Magdalena J.; Taylor, Reid N.; Freeman, Katie T.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2010-01-01

    For many patients, pain is the first sign of cancer and, while pain can be present at any time, the frequency and intensity of pain tend to increase with advancing stages of the disease. Thus, between 75 and 90% of patients with metastatic or advanced-stage cancer will experience significant cancer-induced pain. One major unanswered question is why cancer pain increases and frequently becomes more difficult to fully control with disease progression. To gain insight into this question we used a mouse model of bone cancer pain to demonstrate that as tumor growth progresses within bone, Tropomyosin receptor kinase A (TrkA)-expressing sensory and sympathetic nerve fibers undergo profuse sprouting and form neuroma-like structures. To address what is driving the pathological nerve reorganization we administered an antibody to nerve growth factor (anti-NGF). Early sustained administration of anti-NGF, whose cognate receptor is TrkA, blocks the pathological sprouting of sensory and sympathetic nerve fibers, the formation of neuroma-like structures, and inhibits the development of cancer pain. These results suggest that cancer cells and their associated stromal cells release NGF, which induces a pathological remodeling of sensory and sympathetic nerve fibers. This pathological remodeling of the peripheral nervous system then participates in driving cancer pain. Similar to therapies that target the cancer itself, the data presented here suggest that the earlier that therapies blocking this pathological nerve remodeling are initiated, the more effective the control of cancer pain. PMID:20851743

  5. Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

    PubMed Central

    Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

    2014-01-01

    Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

  6. Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration.

    PubMed

    Ali, Sumia; Driscoll, Heather E; Newton, Victoria L; Gardiner, Natalie J

    2014-11-01

    Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

  7. Use of nerve elongator to repair short-distance peripheral nerve defects: a prospective randomized study

    PubMed Central

    Bai, Lu; Wang, Tian-bing; Wang, Xin; Zhang, Wei-wen; Xu, Ji-hai; Cai, Xiao-ming; Zhou, Dan-ya; Cai, Li-bing; Pan, Jia-dong; Tian, Min-tao; Chen, Hong; Zhang, Dian-ying; Fu, Zhong-guo; Zhang, Pei-xun; Jiang, Bao-guo

    2015-01-01

    Repair techniques for short-distance peripheral nerve defects, including adjacent joint flexion to reduce the distance between the nerve stump defects, “nerve splint” suturing, and nerve sleeve connection, have some disadvantages. Therefore, we designed a repair technique involving intraoperative tension-free application of a nerve elongator and obtained good outcomes in the repair of short-distance peripheral nerve defects in a previous animal study. The present study compared the clinical outcomes between the use of this nerve elongator and performance of the conventional method in the repair of short-distance transection injuries in human elbows. The 3-, 6-, and 12-month postoperative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the conventional group, but no significant difference in long-term neurological function recovery was detected between the two groups. In the nerve elongation group, the nerves were sutured without tension, and the duration of postoperative immobilization of the elbow was decreased. Elbow function rehabilitation was significantly better in the nerve elongation group than in the control group. Moreover, there were no security risks. The results of this study confirm that the use of this nerve elongator for repair of short-distance peripheral nerve defects is safe and effective. PMID:25788924

  8. [Anatomical variants of the medial calcaneal nerve and the Baxter nerve in the tarsal tunnel].

    PubMed

    Martín-Oliva, X; Elgueta-Grillo, J; Veliz-Ayta, P; Orosco-Villaseñor, S; Elgueta-Grillo, M; Viladot-Perice, R

    2013-01-01

    The tarsal tunnel is composed of the posterior border of the medial malleoulus, the posterior aspect of the talus and the medial aspect of the calcaneus. The medial calcaneal nerve emerges from the posterior aspect of the posterior tibial nerve in 75% of cases and from the lateral plantar nerve in the remaining 25%. Finally, the medial calcaneal nerve ends as a single terminal branch in 79% of cases and in numerous terminal branches in the remaining 21%. To describe the anatomical variants of the posterior tibial nerve and its terminal branches. To describe the steps for tarsal tunnel release. To describe Baxter nerve release. The anatomical variants of the posterior tibial nerve and its terminal branches within the tarsal tunnel were studied. Then the Lam technique was performed; it consists of: 1) opening of the laciniate ligament, 2) opening of the fascia over the abductor hallucis muscle, 3) exoneurolysis of the posterior tibial nerve and its terminal branches, identifying the emergence and pathway of the medial calcaneal branch, the lateral plantar nerve and its Baxter nerve branch and the medial plantar nerve. Baxter nerve was found in 100% of cases. In 100% of cases in our series the nerve going to the abductor digiti minimi muscle of the foot was found; 87.5% of cases had two terminal branches. The dissections proved that a crucial step was the release of the distal tarsal tunnel. PMID:24701749

  9. Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve defects

    PubMed Central

    Biazar, Esmaeil; Keshel, Saeed Heidari; Pouya, Majid; Rad, Hadi; Nava, Melody Omrani; Azarbakhsh, Mohammad; Hooshmand, Shirin

    2013-01-01

    It has been confirmed that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson's trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit is suitable for repair of long-segment sciatic nerve defects. PMID:25206536

  10. Distribution of sodium channels during nerve elongation in rat peripheral nerve.

    PubMed

    Ichimura, Harumitsu; Shiga, Takashi; Abe, Ichiro; Hara, Yuki; Terui, Naoto; Tsujino, Akihito; Ochiai, Naoyuki

    2005-01-01

    A number of studies have investigated electrophysiological and morphological changes of peripheral nerves during gradual elongation. There has been, however, no report on the distribution of sodium channels at Ranvier's nodes during peripheral nerve elongation. We investigated peripheral nerve injury after the gradual elongation of rat sciatic nerves. Indirect nerve elongation was induced by leg lengthening at a rate of 3 mm/day by 15 or 30 mm. At 7 days after the leg lengthening, the electrophysiological properties of sciatic nerves, the ultrastructures of the Ranvier's nodes and axons, and the distribution of voltage-dependent sodium channels were examined. In the control nerves, most sodium channels were localized at Ranvier's nodes in myelinated axons, providing the physiological basis of saltatory conduction. In the elongated nerves, both the amplitude and conduction velocity of compound nerve action potential decreased following leg lengthening. The elongated nerves also showed paranodal demyelination in Ranvier's nodes longer than those in the control group. In addition, the distribution of sodium channels became diffuse or disappeared at Ranvier's nodes of elongated nerves. The diffuse distribution and/or disappearance of sodium channels may underlie the electrophysiological changes in compound nerve action potential induced by nerve elongation. PMID:15815871

  11. SOCS3 deletion promotes optic nerve regeneration in vivo

    PubMed Central

    Smith, Patrice D.; Sun, Fang; Park, Kevin Kyungsuk; Cai, Bin; Wang, Chen; Kuwako, Kenichiro; Martinez-Carrasco, Irene; Connolly, Lauren; He, Zhigang

    2009-01-01

    SUMMARY Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3), in adult retinal ganglion cells (RGCs), promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient up-regulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury. PMID:20005819

  12. Magnetic resonance imaging of optic nerve

    PubMed Central

    Gala, Foram

    2015-01-01

    Optic nerves are the second pair of cranial nerves and are unique as they represent an extension of the central nervous system. Apart from clinical and ophthalmoscopic evaluation, imaging, especially magnetic resonance imaging (MRI), plays an important role in the complete evaluation of optic nerve and the entire visual pathway. In this pictorial essay, the authors describe segmental anatomy of the optic nerve and review the imaging findings of various conditions affecting the optic nerves. MRI allows excellent depiction of the intricate anatomy of optic nerves due to its excellent soft tissue contrast without exposure to ionizing radiation, better delineation of the entire visual pathway, and accurate evaluation of associated intracranial pathologies. PMID:26752822

  13. Intercostal nerve conduction study in man.

    PubMed Central

    Pradhan, S; Taly, A

    1989-01-01

    A new surface technique for the conduction study of the lower intercostal nerves has been developed and applied to 30 normal subjects. The problem of the short available nerve segment of the intercostal nerves and the bizzare compound motor action potential (CMAP) of inconsistent latency while recording over the intercostal muscles, is overcome by applying recording electrodes over the rectus abdominis muscle and stimulating the nerves at two points at a fair distance away. With the use of multiple recording sites over the rectus abdominis, the motor points for different intercostal nerves were delineated. CMAP of reproducible latencies and waveforms with sharp take-off points were obtained. Conduction velocity of the intercostal nerves could be determined. PMID:2526200

  14. Neurophysiological approach to disorders of peripheral nerve.

    PubMed

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological methods including nerve conduction studies and electromyography used in the study of patients suspected of having a neuropathy and the significance of the findings are discussed in detail and more novel and experimental methods are mentioned. Diagnostic considerations are based on a flow chart classifying neuropathies into eight categories based on mode of onset, distribution, and electrophysiological findings, and the electrophysiological characteristics in each type of neuropathy are discussed. PMID:23931776

  15. A novel chondroitin sulfate hydrogel for nerve repair

    NASA Astrophysics Data System (ADS)

    Conovaloff, Aaron William

    Brachial plexus injuries affect numerous patients every year, with very debilitating results. The majority of these cases are very severe, and involve damage to the nerve roots. To date, repair strategies for these injuries address only gross tissue damage, but do not supply cells with adequate regeneration signals. As a result, functional recovery is often severely lacking. Therefore, a chondroitin sulfate hydrogel that delivers neurotrophic signals to damaged neurons is proposed as a scaffold to support nerve root regeneration. Capillary electrophoresis studies revealed that chondroitin sulfate can physically bind with a variety of neurotrophic factors, and cultures of chick dorsal root ganglia demonstrated robust neurite outgrowth in chondroitin sulfate hydrogels. Outgrowth in chondroitin sulfate gels was greater than that observed in control gels of hyaluronic acid. Furthermore, the chondroitin sulfate hydrogel's binding activity with nerve growth factor could be enhanced by incorporation of a synthetic bioactive peptide, as revealed by fluorescence recovery after photobleaching. This enhanced binding was observed only in chondroitin sulfate gels, and not in hyaluronic acid control gels. This enhanced binding activity resulted in enhanced dorsal root ganglion neurite outgrowth in chondroitin sulfate gels. Finally, the growth of regenerating dorsal root ganglia in these gels was imaged using label-free coherent anti-Stokes scattering microscopy. This technique generated detailed, high-quality images of live dorsal root ganglion neurites, which were comparable to fixed, F-actin-stained samples. Taken together, these results demonstrate the viability of this chondroitin sulfate hydrogel to serve as an effective implantable scaffold to aid in nerve root regeneration.

  16. [Morphological and functional studies on nerve regeneration after corneal nerve injuries].

    PubMed

    Zhang, Z Q; Xie, L X; Dong, X G

    1994-07-01

    Using gold chloride impregnation of nerves and horse-radish peroxidase (HRP) axoplasma retrograde tracing technique, we monitored nerve regeneration over a period of 6 months following penetrating perilimbal incisions and penetrating keratoplasties (PKP) in rabbits. Post-operatively, at 1 month after a 180 degrees perilimbal incision, loose unconnected subepithelial plexus were present in the limbus, at 2 months 1-2 bundles of deep stromal nerve were seen in the stroma and by 6 months only a few stromal nerves regenerated. There was no difference in nerve regeneration between post-operative autograft and allograft PKP. By 6 months, the quantity of HRP-labelled cells in the trigeminal ganglia was less than the normal level. The results indicated that nerve regeneration by 6 months after corneal nerve injuries was inadequate to restore a normal corneal nerve extent and function. PMID:7843026

  17. Function electrical stimulation signals generator circuits for the central nerve and the sciatic nerve.

    PubMed

    Wenyuan, Li; Zhenyu, Zhang; Zhi-Gong, Wang

    2005-01-01

    Circuits for the signal generation of the FES (functional electrical stimulation) of the central nerve and the sciatic nerve have been designed. The circuits were implemented by using discrete devices. The FES circuits consist of two or three operational amplifiers. The bandwidths of the circuits are more than 10 kHz and their gains are variable from 20 dB to 60 dB. To a load of several kilo-ohms, according to the microelectrode with the nerve, the circuit for stimulating central nerve can provide a current signal, and the signal value is more than 1mA. The circuit for stimulating sciatic nerve can provide a stimulating voltage signal of more than 10 Vs. The loads of the circuits are microelectrodes contacted with nerves. The circuits can be used with two kinds of microelectrodes: cuff microelectrodes which for stimulating sciatic nerve and shaft microelectrodes which for stimulating central nerve. PMID:17281443

  18. Disorders of Cranial Nerves IX and X

    PubMed Central

    Erman, Audrey B.; Kejner, Alexandra E.; Hogikyan, Norman D.; Feldman, Eva L.

    2014-01-01

    The glossopharyngeal and vagus nerves mediate the complex interplay between the many functions of the upper aerodigestive tract. Defects may occur anywhere from the brainstem to the peripheral nerve and can result in significant impairment in speech, swallowing, and breathing. Multiple etiologies can produce symptoms. This review will broadly examine the normal functions, clinical examination, and various pathologies of cranial nerves IX and X. PMID:19214937

  19. Autograft Substitutes: Conduits and Processed Nerve Allografts.

    PubMed

    Safa, Bauback; Buncke, Gregory

    2016-05-01

    Manufactured conduits and allografts are viable alternatives to direct suture repair and nerve autograft. Manufactured tubes should have gaps less than 10 mm, and ideally should be considered as an aid to the coaptation. Processed nerve allograft has utility as a substitute for either conduit or autograft in sensory nerve repairs. There is also a growing body of evidence supporting their utility in major peripheral nerve repairs, gap repairs up to 70 mm in length, as an alternative source of tissue to bolster the diameter of a cable graft, and for the management of neuromas in non-reconstructable injuries. PMID:27094886

  20. Nerve Transfers to Restore Shoulder Function.

    PubMed

    Leechavengvongs, Somsak; Malungpaishorpe, Kanchai; Uerpairojkit, Chairoj; Ng, Chye Yew; Witoonchart, Kiat

    2016-05-01

    The restoration of shoulder function after brachial plexus injury represents a significant challenge facing the peripheral nerve surgeons. This is owing to a combination of the complex biomechanics of the shoulder girdle, the multitude of muscles and nerves that could be potentially injured, and a limited number of donor options. In general, nerve transfer is favored over tendon transfer, because the biomechanics of the musculotendinous units are not altered. This article summarizes the surgical techniques and clinical results of nerve transfers for restoration of shoulder function. PMID:27094888

  1. NERVE AS MODEL TEMPERATURE END ORGAN

    PubMed Central

    Bernhard, C. G.; Granit, Ragnar

    1946-01-01

    Rapid local cooling of mammalian nerve sets up a discharge which is preceded by a local temperature potential, the cooled region being electronegative relative to a normal portion of the nerve. Heating the nerve locally above its normal temperature similarly makes the heated region electronegative relative to a region at normal temperature, and again a discharge is set up from the heated region. These local temperature potentials, set up by the nerve itself, are held to serve as "generator potentials" and the mechanism found is regarded as the prototype for temperature end organs. PMID:19873460

  2. Raman microspectroscopy for visualization of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Minamikawa, Takeo; Harada, Yoshinori; Koizumi, Noriaki; Takamatsu, Tetsuro

    2013-02-01

    The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery is essential for improving quality of life of patients. To preserve peripheral nerves, detection of ne peripheral nerves that cannot be identi ed by human eye or under white light imaging is necessary. In this study, we sought to provide a proof-of-principle demonstration of a label-free detection technique of peripheral nerve tissues against adjacent tissues that employs spontaneous Raman microspectroscopy. A line-illumination confocal Raman microscope was used for the experiment. A laser operating at the wavelength of 532 nm was used as an excitation laser light. We obtained Raman spectra of peripheral nerve, brous connective tissue, skeletal muscle, blood vessel, and adipose tissue of Wistar rats, and extracted speci c spectral features of peripheral nerves and adjacent tissues. By applying multivariate image analysis, peripheral nerves were clearly detected against adjacent tissues without any preprocessing neither xation nor staining. These results suggest the potential of the Raman spectroscopic observation for noninvasive and label-free nerve detection, and we expect this method could be a key technique for nerve-sparing surgery.

  3. Principles and pitfalls of nerve conduction studies.

    PubMed

    Kimura, J

    1984-10-01

    This report reviews the fundamental principles and the changing concepts of nerve stimulation techniques, and discusses the proper application of these techniques in the differential diagnosis of peripheral nerve disorders. Nerve conduction studies help delineate the extent and distribution of the neural lesion and distinguish two major categories of peripheral nerve disease: demyelination and axonal degeneration. Although the method is based on simple principles, pitfalls abound in practice. Variability in nerve conduction measurement may result from temperature change, variations among nerve segments, and the effects of age. Other sources of error include excessive spread of stimulation current, anomalous innervation, temporal dispersion, and inaccuracy of surface measurement. Unlike a bipolar derivation, which selectively records near-field potentials, a referential recording may give rise to stationary far-field peaks from a moving source. Overlooking this possibility can lead to an incorrect interpretation of findings. Conventional nerve conduction studies deal primarily with measurements of the distal nerve segments in an extremity. More recent techniques are applicable to less accessible anatomical regions, as illustrated by elicitation of the blink reflex, F wave, and H reflex, and the use of the inching technique. Other methods used to assess special aspects of nerve conduction include the ischemic test and studies of slow-conducting fibers. PMID:6093680

  4. Peripheral nerve injuries in the athlete.

    PubMed

    Feinberg, J H; Nadler, S F; Krivickas, L S

    1997-12-01

    Peripheral nerves are susceptible to injury in the athlete because of the excessive physiological demands that are made on both the neurological structures and the soft tissues that protect them. The common mechanisms of injury are compression, traction, ischaemia and laceration. Seddon's original classification system for nerve injuries based on neurophysiological changes is the most widely used. Grade 1 nerve injury is a neuropraxic condition, grade 2 is axonal degeneration and grade 3 is nerve transection. Peripheral nerve injuries are more common in the upper extremities than the lower extremities, tend to be sport specific, and often have a biomechanical component. While the more acute and catastrophic neurological injuries are usually obvious, many remain subclinical and are not recognised before neurological damage is permanent. Early detection allows initiation of a proper rehabilitation programme and modification of biomechanics before the nerve injury becomes irreversible. Recognition of nerve injuries requires an understanding of peripheral neuroanatomy, knowledge of common sites of nerve injury and an awareness of the types of peripheral nerve injuries that are common and unique to each sport. The electrodiagnostic exam, usually referred to as the 'EMG', consists of nerve conduction studies and the needle electrode examination. It is used to determine the site and degree of neurological injury and to predict outcome. It should be performed by a neurologist or physiatrist (physician specialising in physical medicine and rehabilitation), trained and skilled in this procedure. Timing is essential if the study is to provide maximal information. Findings such as decreased recruitment after injury and conduction block at the site of injury may be apparent immediately after injury but other findings such as abnormal spontaneous activity may take several weeks to develop. The electrodiagnostic test assists with both diagnosis of the injury and in predicting

  5. Tissue engineered constructs for peripheral nerve surgery

    PubMed Central

    Johnson, P. J.; Wood, M. D.; Moore, A. M.; Mackinnon, S. E.

    2013-01-01

    Summary Background Tissue engineering has been defined as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ”. Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. Methods A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. Results Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. Conclusions The field of tissue engineering should consider its challenge to not only meet the autograft “gold standard” but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft. PMID:24385980

  6. Hypoxia inhibits abdominal expiratory nerve activity.

    PubMed

    Fregosi, R F; Knuth, S L; Ward, D K; Bartlett, D

    1987-07-01

    Our purpose was to examine the influence of steady-state changes in chemical stimuli, as well as discrete peripheral chemoreceptor stimulation, on abdominal expiratory motor activity. In decerebrate, paralyzed, vagotomized, and ventilated cats that had bilateral pneumothoraces, we recorded efferent activity from a phrenic nerve and from an abdominal nerve (cranial iliohypogastric nerve, L1). All cats showed phasic expiratory abdominal nerve discharge at normocapnia [end-tidal PCO2 38 +/- 2 Torr], but small doses (2-6 mg/kg) of pentobarbital sodium markedly depressed this activity. Hyperoxic hypercapnia consistently enhanced abdominal expiratory activity and shortened the burst duration. Isocapnic hypoxia caused inhibition of abdominal nerve discharge in 11 of 13 cats. Carotid sinus nerve denervation (3 cats) exacerbated the hypoxic depression of abdominal nerve activity and depressed phrenic motor output. Stimulation of peripheral chemoreceptors with NaCN increased abdominal nerve discharge in 7 of 10 cats, although 2 cats exhibited marked inhibition. Four cats with intact neuraxis, but anesthetized with ketamine, yielded qualitatively similar results. We conclude that when cats are subjected to steady-state chemical stimuli in isolation (no interference from proprioceptive inputs), hypercapnia potentiates, but hypoxia attenuates, abdominal expiratory nerve activity. Mechanisms to explain the selective inhibition of expiratory motor activity by hypoxia are proposed, and physiological implications are discussed. PMID:3624126

  7. Interventional nerve visualization via the intrinsic anisotropic optical properties of the nerves

    NASA Astrophysics Data System (ADS)

    Chin, Kenneth W.; Meijerink, Andries; Chin, Patrick T. K.

    2015-07-01

    We present an optical concept to visualize nerves during surgical interventions. The concept relies on the anisotropic optical properties of the nerves which allows for specific switching of the optical reflection by the nervous tissue. Using a low magnification polarized imaging system we are able to visualize the on and off switching of the optical reflection of the nervous tissue, enabling a non-invasive nerve specific real-time nerve visualization during surgery.

  8. Mice Lacking GD3 Synthase Display Morphological Abnormalities in the Sciatic Nerve and Neuronal Disturbances during Peripheral Nerve Regeneration

    PubMed Central

    Ribeiro-Resende, Victor Túlio; Gomes, Tiago Araújo; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  9. Mice lacking GD3 synthase display morphological abnormalities in the sciatic nerve and neuronal disturbances during peripheral nerve regeneration.

    PubMed

    Ribeiro-Resende, Victor Túlio; Araújo Gomes, Tiago; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  10. Earthworm extracts facilitate PC12 cell differentiation and promote axonal sprouting in peripheral nerve injury.

    PubMed

    Chen, Chao-Tsung; Lin, Jaung-Geng; Lu, Tung-Wu; Tsai, Fuu-Jen; Huang, Chih-Yang; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2010-01-01

    The present study provides in vitro and in vivo evaluations of earthworm (Pheretima aspergilum) on peripheral nerve regeneration. In the in vitro study, we found the earthworm (EW) water extracts caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as the expressions of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with EW extracts were used to bridge a 10 mm sciatic nerve defect in rats. Eight weeks after implantation, the group receiving EW extracts had a much higher success percentage of regeneration (90%) compared to the control (60%) receiving the saline. In addition, quantitative histology of the successfully regenerated nerves revealed that myelinated axons in EW group at 31.25 microg/ml was significantly more than those in the controls (p < 0.05). These results showed that EW extracts can be a potential growth-promoting factor on regenerating peripheral nerves. PMID:20503471

  11. Swimming behaviour and calcium incorporation into inner ear otoliths of fish after vestibular nerve transection.

    PubMed

    Edelmann, E; Anken, R H; Rahmann, H

    2004-01-01

    Previous investigations on neonate swordtail fish (Xiphophorus helleri) revealed that otolithic calcium incorporation (visualized using the calcium tracer alizarin complexone) and thus otolith growth had ceased after nerve transection, supporting a hypothesis according to which the gravity-dependent otolith growth is regulated neuronally. Subsequent investigations on larval cichlid fish (Oreochromis mossambicus) yielded contrasting results, repeatedly depend