BACKGROUND： Previous studies have shown that nerve regeneration factor （NRF） provides neuroprotective effects. However, the neuroprotective effects on retinal ganglion cells in an animal model of glaucoma remain un...BACKGROUND： Previous studies have shown that nerve regeneration factor （NRF） provides neuroprotective effects. However, the neuroprotective effects on retinal ganglion cells in an animal model of glaucoma remain uncertain. OBJECTIVE： To determine the neuroprotective effects of NRF on retinal ganglion cells in a rabbit model of acute hyper-intraocular pressure and to compare the effects on brain-derived neurotrophic factor （BDNF）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at Jiangsu Provincial Key Laboratory of Neural Regeneration from September 2006 to August 2007. MATERIALS： Sterone, a major component of NRF, was provided by the Key Laboratory of Neural Regeneration, Nantong University in China; BDNF was provided by BioDesign Inc., USA. METHODS： A total of 24 healthy rabbits were randomly assigned to NRF, BDNF, and phosphate buffered saline groups, with 8 rabbits per group. The left eyes were considered normal controls, and acute hyper-intraocular pressure was induced in the right eyes via anterior chamber perfusion. The right camera vitrea bulbi was injected with 4.5 μg NRF, 3.75 μg BDNF, or 5 μL 0.1 mol/L phosphate buffered saline, respectively. MAIN OUTCOME MEASURES： Retinal ganglion cells were reverse-labeled using horseradish peroxidase to quantify cell density at 2, 4, and 6 mm from the optic disc edge. RESULTS： NRF increased the number of surviving retinal ganglion cells at the optic disc edge （P 〈 0.01 or P 〈 0.05）. The density of surviving retinal ganglion cells decreased with increasing distance from the optic disc. The number of retinal ganglion cells in the BDNF group was similar to the NRF group （P 〉 0.05）. At 2, 4, and 6 mm away from the optic disc edge, there was no significant difference in retinal ganglion cell density between NRF and BDNF groups （P〉 0.05）. CONCLUSION： NRF provided protection to retinal ganglion cells in a rabbit model of acute hyper-intraocular pressure, Le., NRF enhanced the survival rate of retinal ganglion cells. The neuroprotective effect was similar to BDNF.展开更多
Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulat...Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulation to induce neurite outgrowth. In the present study, short-term, low-frequency electrical stimulation, using identical stimulation parameters of in vivo experiments, was administered to in vitro dorsal root ganglion （DRG） neurons. Enhanced neurite outgrowth, as well as synthesis and release of brain-derived neurotrophic factor （BDNF）, were examined in electrical stimulation-treated DRG neuronal cultures. Because the effects of electrical stimulation on neuronal intracellular signaling molecules are less reported, classic calcium intracellular signals are directly or indirectly involved in electrical stimulation effects on neurons. Cultured DRG neurons were pretreated with the calcium channel blocker nifedipine, followed by electrical stimulation. Results suggested that electrical stimulation not only promoted in vitro neurite outgrowth, but also enhanced BDNF expression. However, nifedipine reduced electrical stimulation-enhanced neurite outgrowth and BDNF biosynthesis. These results suggest that the promoting effects of electrical stimulation on DRG neurite outgrowth could be associated with altered calcium influx, which is involved induction of neuronal BDNF expression and secretion.展开更多
Studies have shown that retreatment of the distal stoma after nerve grafting can stimulate nerve regeneration. The present study attempted to verify the effects of reanastomosis of the distal stoma, after nerve grafti...Studies have shown that retreatment of the distal stoma after nerve grafting can stimulate nerve regeneration. The present study attempted to verify the effects of reanastomosis of the distal stoma, after nerve grafting, on nerve regeneration by assessing brain-derived neurotrophic factor expression in 2-month-old rats. Results showed that brain-derived neurotrophic factor expression in L2-4 dorsal root ganglia began to increase 3 days after autologous nerve grafting post sciatic nerve injury, peaked at 14 days, decreased at 28 days, and reached similar levels to the sham-surgery group at 56 days. Brain-derived neurotrophic factor expression in L2-4 dorsal root ganglia began to increase 3 days after reanastomosis of the distal stoma, 59 days after autologous nerve grafting post sciatic nerve injury, significantly increased at 63 days, peaked at 70 days, and gradually decreased thereafter, but remained higher compared with the sham-surgery group up to 112 days. The results of this study indicate that reanastomosis of the distal stoma after orthotopic nerve grafting stimulated brain-derived neurotrophic factor expression in L2.4 dorsal root ganglia.展开更多
This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of...This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly（lactide-co-glycolide） nanoparticles on this injury was then analyzed. Dorsal root ganglion cells （LT） of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1,2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome.展开更多
文摘BACKGROUND： Previous studies have shown that nerve regeneration factor （NRF） provides neuroprotective effects. However, the neuroprotective effects on retinal ganglion cells in an animal model of glaucoma remain uncertain. OBJECTIVE： To determine the neuroprotective effects of NRF on retinal ganglion cells in a rabbit model of acute hyper-intraocular pressure and to compare the effects on brain-derived neurotrophic factor （BDNF）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at Jiangsu Provincial Key Laboratory of Neural Regeneration from September 2006 to August 2007. MATERIALS： Sterone, a major component of NRF, was provided by the Key Laboratory of Neural Regeneration, Nantong University in China; BDNF was provided by BioDesign Inc., USA. METHODS： A total of 24 healthy rabbits were randomly assigned to NRF, BDNF, and phosphate buffered saline groups, with 8 rabbits per group. The left eyes were considered normal controls, and acute hyper-intraocular pressure was induced in the right eyes via anterior chamber perfusion. The right camera vitrea bulbi was injected with 4.5 μg NRF, 3.75 μg BDNF, or 5 μL 0.1 mol/L phosphate buffered saline, respectively. MAIN OUTCOME MEASURES： Retinal ganglion cells were reverse-labeled using horseradish peroxidase to quantify cell density at 2, 4, and 6 mm from the optic disc edge. RESULTS： NRF increased the number of surviving retinal ganglion cells at the optic disc edge （P 〈 0.01 or P 〈 0.05）. The density of surviving retinal ganglion cells decreased with increasing distance from the optic disc. The number of retinal ganglion cells in the BDNF group was similar to the NRF group （P 〉 0.05）. At 2, 4, and 6 mm away from the optic disc edge, there was no significant difference in retinal ganglion cell density between NRF and BDNF groups （P〉 0.05）. CONCLUSION： NRF provided protection to retinal ganglion cells in a rabbit model of acute hyper-intraocular pressure, Le., NRF enhanced the survival rate of retinal ganglion cells. The neuroprotective effect was similar to BDNF.
基金the Shanghai Leading Academic Discipline Project,No.S30201the Doctoral Research Foundation of Nanchang University
文摘Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulation to induce neurite outgrowth. In the present study, short-term, low-frequency electrical stimulation, using identical stimulation parameters of in vivo experiments, was administered to in vitro dorsal root ganglion （DRG） neurons. Enhanced neurite outgrowth, as well as synthesis and release of brain-derived neurotrophic factor （BDNF）, were examined in electrical stimulation-treated DRG neuronal cultures. Because the effects of electrical stimulation on neuronal intracellular signaling molecules are less reported, classic calcium intracellular signals are directly or indirectly involved in electrical stimulation effects on neurons. Cultured DRG neurons were pretreated with the calcium channel blocker nifedipine, followed by electrical stimulation. Results suggested that electrical stimulation not only promoted in vitro neurite outgrowth, but also enhanced BDNF expression. However, nifedipine reduced electrical stimulation-enhanced neurite outgrowth and BDNF biosynthesis. These results suggest that the promoting effects of electrical stimulation on DRG neurite outgrowth could be associated with altered calcium influx, which is involved induction of neuronal BDNF expression and secretion.
基金supported by the Key Project of Clinical Subject of the Health Ministry,China (2010-2012),No.[2010]439
文摘Studies have shown that retreatment of the distal stoma after nerve grafting can stimulate nerve regeneration. The present study attempted to verify the effects of reanastomosis of the distal stoma, after nerve grafting, on nerve regeneration by assessing brain-derived neurotrophic factor expression in 2-month-old rats. Results showed that brain-derived neurotrophic factor expression in L2-4 dorsal root ganglia began to increase 3 days after autologous nerve grafting post sciatic nerve injury, peaked at 14 days, decreased at 28 days, and reached similar levels to the sham-surgery group at 56 days. Brain-derived neurotrophic factor expression in L2-4 dorsal root ganglia began to increase 3 days after reanastomosis of the distal stoma, 59 days after autologous nerve grafting post sciatic nerve injury, significantly increased at 63 days, peaked at 70 days, and gradually decreased thereafter, but remained higher compared with the sham-surgery group up to 112 days. The results of this study indicate that reanastomosis of the distal stoma after orthotopic nerve grafting stimulated brain-derived neurotrophic factor expression in L2.4 dorsal root ganglia.
基金supported by grants from the Medical Scientific Fund and Intensive Research of Nanjing Military Area Command of Chinese PLA, No.Nan2007-13 and Nan 08Z003the Medical Scientific Fund and Research of Chinese PLA during the 12th Five-Year Plan Period,No.CWS11J260
文摘This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly（lactide-co-glycolide） nanoparticles on this injury was then analyzed. Dorsal root ganglion cells （LT） of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1,2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome.
