Background Spinal cord injury （SCI） is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic fact...Background Spinal cord injury （SCI） is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor （GDNF） mediated by recombinant adeno-associated virus type 2 （rAAV2） alone or in combination with early rehabilitation training on SCI. Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups： natural healing group, gene therapy group, rehabilitation training group, and combination therapy group （gene therapy in combination with rehabilitation training）. Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma. Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days. Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.展开更多
Aim:Previous studies show enteric glia(EG)-conditioned medium promotes neurite outgrowth in adult dorsal root ganglia(DRG)derived sensory neurons.This EG-conditioned medium contains various neurotrophic factors,includ...Aim:Previous studies show enteric glia(EG)-conditioned medium promotes neurite outgrowth in adult dorsal root ganglia(DRG)derived sensory neurons.This EG-conditioned medium contains various neurotrophic factors,including nerve growth factor(NGF),brain-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 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 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 medium to evaluate the factor’s individual importance in preventing growth cone collapse.Results:EG-conditioned medium inhibits and reverses growth cone collapse in adult DRG neurons when added either 1 h before or concurrently with SEMA3A.When administered 40 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.展开更多
基金The study was supported by the National Natural Science Foundation of China （No. 30970880）, the Natural Science Foundation of the Jiangsu Province （No. BK20130342）, and the Jiangsu Planned Projects for Postdoctoral Research Funds （No. 1301069C）.
文摘Background Spinal cord injury （SCI） is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor （GDNF） mediated by recombinant adeno-associated virus type 2 （rAAV2） alone or in combination with early rehabilitation training on SCI. Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups： natural healing group, gene therapy group, rehabilitation training group, and combination therapy group （gene therapy in combination with rehabilitation training）. Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma. Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days. Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.
基金supported by Canadian Spinal Research Organization#84831.
文摘Aim:Previous studies show enteric glia(EG)-conditioned medium promotes neurite outgrowth in adult dorsal root ganglia(DRG)derived sensory neurons.This EG-conditioned medium contains various neurotrophic factors,including nerve growth factor(NGF),brain-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 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 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 medium to evaluate the factor’s individual importance in preventing growth cone collapse.Results:EG-conditioned medium inhibits and reverses growth cone collapse in adult DRG neurons when added either 1 h before or concurrently with SEMA3A.When administered 40 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.
