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  • articleNo Access

    Locally Administered Nerve Growth Factor Suppresses Ginsenoside Rb1-enhanced Peripheral Nerve Regeneration

    A high-dose of nerve growth factor (NGF) mixed with ginsenoside Rb1(GRb1) was encapsulated by collagen and placed in silicone rubber chambers, which were used to repair dissected Sprague-Dawley rat sciatic nerves with 15 mm gaps. Six weeks after surgery, no axons or Schwann cells were seen in these chambers. By comparison, nerves treated with collagen-GRb1 alone had regenerated axons and Schwann cells in their endoneurial areas. We suggest that excessive NGF may not promote but, rather, suppress developing nerves.

  • articleNo Access

    The Effect of Herbal Medicine on Nerve Growth Factor in Estradiol Valerate-induced Polycystic Ovaries in Rats

    A type of polycystic ovary resembling some aspects of human polycystic ovarian syndrome (PCOS) can be induced in the rat with a single injection of long-acting estradiol valerate. Among several theories behind the development of polycystic ovaries (PCO), the involvement of the sympathetic nervous system draws much attention, and herbal medicine is known to relieve the abnormal symptoms of PCO. Two herbal formulas, Changbudodam-Tang (cang fu dao tan tang) and Yongdamsagan-Tang (long dan xie gan tang), were used in the present study. The administration of herbal medicine was done every other day for 60 days. The morphological changes of ovaries from herbal medicine treatment were compared to those from an oil-treated control group and an estradiol valerate-injected group. This study also examined the possible hypothesis of neurogenic participation in terms of nerve growth factor (NGF) in the pathology of ovarian dysfunction. The nerve growth factor was analyzed in the central nervous system and ovaries by immunohistochemistry. The main findings of the present study were: (1) PCO were fully developed in rats with a single intramuscular injection of estradiol valerate, (2) PCO resulted in the expression of NGF in the ovaries and the brain tissues, and (3) herbal medicine administration significantly decreased the elevated NGF staining in the ovaries without affecting the brain tissues significantly.

  • articleNo Access

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    • articleOpen Access

      GELATIN-TRICALCIUM PHOSPHATE MEMBRANE MODIFIED WITH NGF AND CULTURED SCHWANN CELLS FOR PERIPHERAL NERVE REPAIR: A TISSUE ENGINEERING APPROACH

      This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously developed gelatin-tricalcium phosphate (GTG) conduits by incorporating them with nerve growth factors and cultured Schwann cells. The nerve growth factors were covalently immobilized onto the GTG conduits (GEN) using carbodiimide. Schwann cells were harvested from neonatal Lewis rats, cultured for seven days and injected into the GEN conduits. The experiment was performed in three groups: GTG conduits, GEN conduits and GEN conduits with Schwann cells injected (GEN+Sc). The effects of different conduits (GTG, GEN and GEN with Schwann cells) on the peripheral nerve regeneration were evaluated in rat sciatic nerve repair model. 24 weeks after implantation of conduits, degradation of the conduits in all groups was illustrated by the fragmentation of the conduits. All conduits were well tolerated by the host tissue. Under microscopic evaluations, regenerated nerve tissue with myelinated and unmyelinated axons presented in all groups. Histomorphometrically, the total nerve area of GEN+Sc group was significantly higher than GTG group. Conversely, the autotomy score evaluated 12 weeks after nerve repair showed better results for GTG group. Besides, GEN+Sc group had the highest average recovery index of compound muscle action potential, but the difference among each group did not reach statistical significance. Although the electrophysiological recovery of nerve was not significantly improved with GEN+Sc conduit, nerve repair using tissue engineered conduits still provided better histological results. However, it should be noticed that autotomy may be the price paid for enhanced peripheral nerve.

    • articleNo Access

      INDUCTION OF NEURONAL DIFFERENTIATION OF EMBRYONIC RAT CORTICAL NEUROSPHERES BY NERVE GROWTH FACTOR AND FETAL BOVINE SERUM ON THE NONADHERENT AND ADHERENT SUBSTRATES

      Regulating neural stem cells will greatly aid in developing regenerative medicine for the repair purpose of central nervous system (CNS). In this study, we explored the effect of nerve growth factor (NGF) on the differentiation of neural stem cells from embryonic rat cerebral cortex on nonadherent and adherent substrates at neurosphere level. The results showed that NGF could not promote adhesion and differentiation of neural stem cells when neurospheres were cultured on nonadherent tissue culture polystyrene (TCPS) substrates under serum-free condition. However, when 10% fetal bovine serum (FBS) was added to the culture system, FBS could induce the attachment of neurospheres onto an originally nonadherent substrate and almost all of the neurosphere-forming cells would migrate away from the spheres with the protoplasmic astrocyte morphology. Furthermore, when NGF was added into the FBS-containing medium, a significant number of differentiated neurons developed and distributed on the astrocyte layer. For comparison, adherent poly-D-lysine (PDL) substrates were also used. It was found that NGF could enhance differentiation of neural stem cells into neurons on PDL under serum-free condition but neurons and astrocytes could not migrate far away from the spheres. Similar to the TCPS results were also observed on PDL that differentiated neurons migrated out from the spheres and developed on the astrocyte layer when the medium contained NGF and FBS. Since the development of neurons needs glia cells to form a cellular substratum and to support neuronal migration to appropriate location, these results provide evidences that FBS-induced glia cells, serving as an architectural support layer, are essential for the growth and migration of NGF-induced neurons.

    • chapterNo Access

      The Synovium of Transgenic Arthritic Mice Expressing Human Tumor Necrosis Factor Contains a High Level of Nerve Growth Factor

      We have recently reported that nerve growth factor (NGF) increases in the synovium of patients affected by rheumatoid arthritis and in the synovium of pharmacologically-induced arthritis in animal models. In the present study, we demonstrate that arthritic transgenic mice which carry and express the human TNF gene (Tgl97) also express elevated levels of NGF, and that subcutaneous injection of NGF-antibodies attenuates the loss of body weight caused by the developement of disease in these mice. Along with our previous findings,which show an increase in the level of NGF during the acute phase of other autoimmune diseases, these results suggest a role of NGF in these pathologies. The functional significance of NGF in rheumatoid arthritis (RA) is currently under study.

    • chapterNo Access

      Increased levels of NGF in sera of systemic lupus erythematosus patients

      USING a specific enzyme-linked immunosorbent assay (ELISA) for human nerve growth factor (NGF), serum levels in patients with systemic lupus erythematosus (SLE) were measured. We found a consistent increase in NGF levels in SLE patients compared with controls. A good correlation exists between serum NGF level and severity of clinical manifestation. We hypothesize that NGF might play a role in the pathogenesis of autoimmune disorders such as SLE.

    • chapterNo Access

      Update of the NGF saga

      Nerve growth factor (NGF), initially characterized for its survival and differentiating actions on embryonic sensory and sympathetic neurons, is now known to display a greatly extended spectrum of biological functions. NGF exerts a profound modulatory role on sensory nociceptive nerve physiology during adulthood which appears to correlate with hyperalgesic phenomena occurring in tissue inflammation. Other newly detected NGF-responsive cells belong to the hematopoietic-immune and neuroendocrine systems. In particular, mast cells and NGF both appear to be involved in neuroimmune interactions and tissue inflammation, with NGF acting as a general “alert” molecule capable of recruiting and priming both local tissue and systemic defense processes following stressful events. NGF can thus be viewed as a multifactorial mediator modulating neuroimmune-endocrine functions of vital importance to the regulation of homeostatic interactions, with potential involvement in pathological processes deriving from dysregulation of either local or systemic homeostatic balances.