Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promis...Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.展开更多
Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury...Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli（ST36）,Xuanzhong（GB39）,Futu（ST32）and Sanyinjiao（SP6）were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase（ACh E）activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor（GDNF）m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.展开更多
Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically re...Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically relevant,standardized rat model of contusion SCI were identified by searching the PubMed,Embase and Cochrane databases,and the extracted data were analyzed by Stata 14.0.Data selection:Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso,Beattie,and Bresnahan lo-comotor rating scale.Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.Outcome measures:The restoration of motor function was assessed by the Basso,Beattie,and Bresnahan locomotor rating scale.Results:We identified 1756 non-duplicated papers by searching the aforementioned electronic databases,and 30 full-text articles met the inclusion criteria.A total of 37 studies reported in the 30 articles were included in the meta-analysis.The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs,to a moderate extent(pooled standardized mean difference(SMD)=0.73;95%confidence interval(CI):0.47–1.00;P<0.001).NSCs obtained from different donor species(rat:SMD=0.74;95%CI:0.36–1.13;human:SMD=0.78;95%CI:0.31–1.25),at different donor ages(fetal:SMD=0.67;95%CI:0.43–0.92;adult:SMD=0.86;95%CI:0.50–1.22)and from different origins(brain-derived:SMD=0.59;95%CI:0.27–0.91;spinal cord-derived:SMD=0.51;95%CI:0.22–0.79)had similar efficacies on improved functional recovery;however,adult induced pluripotent stem cell-derived NSCs showed no significant efficacies.Furthermore,the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery(SMD=0.45;95%CI:0.21–0.70).However,shorter periods between the contusion induction and the NSC transplantation showed slightly higher efficacies(acute:SMD=1.22;95%CI:0.81–1.63;subacute:SMD=0.75;95%CI:0.42–1.09).For chronic injuries,NSC implantation did not significantly improve functional recovery(SMD=0.25;95%CI:–0.16 to 0.65).Conclusion:NSC transplantation alone appears to be a positive yet limited method for the treatment of contusion SCIs.展开更多
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
基金supported by the National Natural Science Foundation of China,No.81671211,81672251(both to HLL)
文摘Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.
基金supported by a grant from the Shaanxi Province Scientific and Technological Project in China,No.2014TM4193
文摘Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli（ST36）,Xuanzhong（GB39）,Futu（ST32）and Sanyinjiao（SP6）were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase（ACh E）activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor（GDNF）m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81171147“Key Medical Talents of Qiangwei Project” Research Foundation of Health Department of Jiangsu Province of China,No.ZDRCA2016010+1 种基金“Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province of China,No.RC201156Jiangsu Provincial Key Discipline of Medicine of China,No.XK201117(all to LXL)
文摘Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically relevant,standardized rat model of contusion SCI were identified by searching the PubMed,Embase and Cochrane databases,and the extracted data were analyzed by Stata 14.0.Data selection:Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso,Beattie,and Bresnahan lo-comotor rating scale.Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.Outcome measures:The restoration of motor function was assessed by the Basso,Beattie,and Bresnahan locomotor rating scale.Results:We identified 1756 non-duplicated papers by searching the aforementioned electronic databases,and 30 full-text articles met the inclusion criteria.A total of 37 studies reported in the 30 articles were included in the meta-analysis.The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs,to a moderate extent(pooled standardized mean difference(SMD)=0.73;95%confidence interval(CI):0.47–1.00;P<0.001).NSCs obtained from different donor species(rat:SMD=0.74;95%CI:0.36–1.13;human:SMD=0.78;95%CI:0.31–1.25),at different donor ages(fetal:SMD=0.67;95%CI:0.43–0.92;adult:SMD=0.86;95%CI:0.50–1.22)and from different origins(brain-derived:SMD=0.59;95%CI:0.27–0.91;spinal cord-derived:SMD=0.51;95%CI:0.22–0.79)had similar efficacies on improved functional recovery;however,adult induced pluripotent stem cell-derived NSCs showed no significant efficacies.Furthermore,the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery(SMD=0.45;95%CI:0.21–0.70).However,shorter periods between the contusion induction and the NSC transplantation showed slightly higher efficacies(acute:SMD=1.22;95%CI:0.81–1.63;subacute:SMD=0.75;95%CI:0.42–1.09).For chronic injuries,NSC implantation did not significantly improve functional recovery(SMD=0.25;95%CI:–0.16 to 0.65).Conclusion:NSC transplantation alone appears to be a positive yet limited method for the treatment of contusion SCIs.
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.
