BACKGROUND： Growth-associated protein-43 （GAP-43） expression in the nervous system has been demonstrated to promote neural regeneration, neuronal growth and development, as well as synaptic reconstruction. Neurofil...BACKGROUND： Growth-associated protein-43 （GAP-43） expression in the nervous system has been demonstrated to promote neural regeneration, neuronal growth and development, as well as synaptic reconstruction. Neurofilament 200 （NF200） expression could reflect degree of injury and repair in injured spinal axons. OBJECTIVE： To observe NF200 expression changes in a rat model of complete spinal cord injury following GAP-43 treatment and to explore the effects of GAP-43 following spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Histology and Embryology of Kunming Medical University between March 2007 and October 2008. MATERIALS： GAP-43 and GAP-43 antibody were provided by Beijing Boao Biology, China; mouse anti-rat NF200 antibody was purchased from Chemicon, USA. METHODS： Female, 8-week-old, Sprague Dawley rats were randomly assigned into three groups following complete spinal cord injury, with 20 animals in each group： GAP-43 antibody, GAP-43, and model groups. In addition, each group was subdivided into four subgroups according to sampling time after modeling, Le., 3-, 5-, 9-, and 15-day groups, with 5 rats in each group. GAP-43 antibody or GAP-43 was injected into injury sites of the spinal cord, 5 μg/0.2 mL, respectively, twice daily for three consecutive days, followed by three additional days of injection, once daily. The model group did not receive any treatment following injury. MAIN OUTCOME MEASURES： NF200 expression in the damaged spinal area at different stages was detected by immunohistochemistry; lower limb motion function following injury was evaluated using the Basso, Beattie and Bresnahan （BBB） locomotor rating scale. RESULTS： NF200 expression was significantly reduced in the GAP-43 antibody group, compared with GAP-43 and model groups, at 3 and 5 days after spinal cord injury （P 〈 0.05）. In addition, the model group expressed significantly less NF200 than the GAP-43 group （P 〈 0.05）. BBB scores from the GAP-43 antibody and model groups were remarkably less than the GAP-43 group （P 〈 0.05）. At 9 and 15 days of injury after drug withdrawal, NF200 expression was increased in the GAP-43 antibody group, and NF200 expression and BBB scores in the GAP-43 antibody and GAP-43 groups were significantly greater than in the model group （P 〈 0.05）. In particular, the GAP-43 group exhibited greater BBB scores than the GAP-43 antibody group at day 9 （P 〈 0.05）. CONCLUSION： GAP-43 promoted NF200 expression and recovery of lower limb function. Early administration of GAP-43 antibody produced reversible nerve inhibition, which was rapidly restored following withdrawal.展开更多
Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functiona...Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen＇s method. The rats were given electroacupuncture treatment at Dazhui（Du14）, Mingmen（Du4）, Sanyinjiao（SP6）, Huantiao（GB30）, Zusanli（ST36） and Kunlun（BL60） acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan（BBB） locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.展开更多
After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether d...After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether direct injection of BMP7 into acutely injured ratalalo createrywith 50 ng BMP7（BMP7 group）or physiological saline（control group）for 7 consecutive days.Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials（MEP）decreased after spinal cord injury.At 8 weeks post-operation,the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group.Basso,Beattie,Bresnahan scale（BBB）scores,hematoxylin-eosin staining,and western blot assay showed that at 1,2,4 and 8 weeks post-operation,BBB scores were increased;Nissl body staining was stronger;the number of Nissl-stained bodies was increased;the number of vacuoles gradually decreased;the number of synapses was increased;and the expression of neuronal marker,neurofilament protein 200,was increased in the hind limbs of the BMP7 group compared with the control group.Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups.These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.展开更多
文摘BACKGROUND： Growth-associated protein-43 （GAP-43） expression in the nervous system has been demonstrated to promote neural regeneration, neuronal growth and development, as well as synaptic reconstruction. Neurofilament 200 （NF200） expression could reflect degree of injury and repair in injured spinal axons. OBJECTIVE： To observe NF200 expression changes in a rat model of complete spinal cord injury following GAP-43 treatment and to explore the effects of GAP-43 following spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Histology and Embryology of Kunming Medical University between March 2007 and October 2008. MATERIALS： GAP-43 and GAP-43 antibody were provided by Beijing Boao Biology, China; mouse anti-rat NF200 antibody was purchased from Chemicon, USA. METHODS： Female, 8-week-old, Sprague Dawley rats were randomly assigned into three groups following complete spinal cord injury, with 20 animals in each group： GAP-43 antibody, GAP-43, and model groups. In addition, each group was subdivided into four subgroups according to sampling time after modeling, Le., 3-, 5-, 9-, and 15-day groups, with 5 rats in each group. GAP-43 antibody or GAP-43 was injected into injury sites of the spinal cord, 5 μg/0.2 mL, respectively, twice daily for three consecutive days, followed by three additional days of injection, once daily. The model group did not receive any treatment following injury. MAIN OUTCOME MEASURES： NF200 expression in the damaged spinal area at different stages was detected by immunohistochemistry; lower limb motion function following injury was evaluated using the Basso, Beattie and Bresnahan （BBB） locomotor rating scale. RESULTS： NF200 expression was significantly reduced in the GAP-43 antibody group, compared with GAP-43 and model groups, at 3 and 5 days after spinal cord injury （P 〈 0.05）. In addition, the model group expressed significantly less NF200 than the GAP-43 group （P 〈 0.05）. BBB scores from the GAP-43 antibody and model groups were remarkably less than the GAP-43 group （P 〈 0.05）. At 9 and 15 days of injury after drug withdrawal, NF200 expression was increased in the GAP-43 antibody group, and NF200 expression and BBB scores in the GAP-43 antibody and GAP-43 groups were significantly greater than in the model group （P 〈 0.05）. In particular, the GAP-43 group exhibited greater BBB scores than the GAP-43 antibody group at day 9 （P 〈 0.05）. CONCLUSION： GAP-43 promoted NF200 expression and recovery of lower limb function. Early administration of GAP-43 antibody produced reversible nerve inhibition, which was rapidly restored following withdrawal.
基金supported by a grant from the Science and Technology Development Program of Jilin Province of China,No.2011084
文摘Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen＇s method. The rats were given electroacupuncture treatment at Dazhui（Du14）, Mingmen（Du4）, Sanyinjiao（SP6）, Huantiao（GB30）, Zusanli（ST36） and Kunlun（BL60） acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan（BBB） locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.
基金supported by the Xinjiang Production and Construction Corps Doctoral Fund of China,No.2014BB020
文摘After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether direct injection of BMP7 into acutely injured ratalalo createrywith 50 ng BMP7（BMP7 group）or physiological saline（control group）for 7 consecutive days.Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials（MEP）decreased after spinal cord injury.At 8 weeks post-operation,the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group.Basso,Beattie,Bresnahan scale（BBB）scores,hematoxylin-eosin staining,and western blot assay showed that at 1,2,4 and 8 weeks post-operation,BBB scores were increased;Nissl body staining was stronger;the number of Nissl-stained bodies was increased;the number of vacuoles gradually decreased;the number of synapses was increased;and the expression of neuronal marker,neurofilament protein 200,was increased in the hind limbs of the BMP7 group compared with the control group.Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups.These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.
