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Feng et al. Neuroimmunol Neuroinflammation 2016;3:180-8          Neuroimmunology and
           DOI: 10.20517/2347-8659.2016.03
                                                                                  Neuroinflammation

                                                                                                www.nnjournal.net
            Original Article                                                                    Open Access


           Inhibition and reversal of growth cone

           collapse in adult sensory neurons by

           enteric glia-induced neurotrophic factors



           Simon Feng , Kiran Reddy , Cai-Xin Su , Shu-Cui Jiang 1,2
                                               1,2
                      1,2
                                   1,2
           1 Department of Surgery (Neurobiology), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
           2 Hamilton NeuroRestorative Group, McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
           Correspondence to: Prof. Shu-Cui Jiang, Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), Head of Hamilton
           NeuroRestorative Group, McMaster University, 1280 Main Street West HSC 4E, Hamilton, ON L8S 4K1, Canada. E-mail: jiangs@mcmaster.ca

           How to cite this article: Feng S, Reddy K, Su CX, Jiang SC. Inhibition and reversal of growth cone collapse in adult sensory neurons by enteric
           glia-induced neurotrophic factors. Neuroimmunol Neuroinflammation 2016;3:180-8.

                                         ABSTRACT
            Article history:              Aim: Previous studies show enteric  glia  (EG)-conditioned  medium  promotes neurite
            Received: 05-01-2016          outgrowth in adult dorsal root ganglia (DRG) derived sensory neurons. This EG-conditioned
            Accepted: 12-07-2016          medium contains various neurotrophic factors, including nerve growth factor (NGF), brain-
            Published: 31-08-2016         derived neurotrophic factor (BDNF), glial cell line-derived neurotropic factor (GDNF), and
                                          neurotrophin-3 (NT-3). This study attempts to determine the importance of these neurotrophic
            Key words:                    factors in enabling DRG-derived sensory neuron axons to overcome the inhibitory guidance
                                          cues released from the glial  scar.  Methods:  A  Semaphorin  3A  (SEMA3A)  growth  cone
            Enteric glia
            growth cone collapse          collapse model was used on cultured rat DRG. Neutralizing antibodies to each neurotrophic
                                          growth factor in question (NGF, BDNF, GDNF and NT-3) were applied to the EG-conditioned
            nerve growth factor           medium to evaluate the factor’s individual importance in preventing growth cone collapse.
            brain-derived neurotrophic factor  Results: EG-conditioned medium inhibits and reverses growth cone collapse in adult DRG
            glial-derived neurotrophic factor  neurons when added either 1 h before or concurrently with SEMA3A. When administered 40
            neurotrophin-3
                                          min after the initial SEMA3A-induced collapse, EG-conditioned medium was able to reverse
                                          the growth cone collapse.  Individual inhibition  of all the neurotrophic factors, except for
                                          BDNF in the co-treatment setting, resulted in increased growth cone collapse. Conclusion:
                                          NGF, BDNF, GDNF, and NT-3 are all variably involved in preventing or reversing SEMA3A-
                                          induced  growth cone  collapse  in  pre-,  co-,  and  post-treatment  time  settings.  However, no
                                          individual neurotrophic factors appear to be essential to promoting neurite outgrowth.


           INTRODUCTION                                       damage occurs in 2 phases: the primary and secondary
                                                              phase. The primary phase is the membrane shearing
           Spinal cord injury (SCI) can result in a complete or partial   and axonal tearing caused by mechanical stress.
                                                                                                             [1]
           loss of sensation and paralysis at and below the site of   The secondary phase is the ischemia, apoptosis, and
           injury and represents a large burden of disease.  SCI   necrosis that occurs post-trauma. [2,3]  Glial scarring at
                                                      [1]
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