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Electroacupuncture promotes the recovery of motor neuron function in the anterior horn of the injured spinal cord 被引量:15
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作者 Jian-hui Yang Jian-guo Lv +1 位作者 Hui Wang Hui-yong Nie 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第12期2033-2039,共7页
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
关键词 nerve regeneration spinal cord injury ELECTROACUPUNCTURE spine injury secondaryinjury ACUPOINT motor neurons ACETYLCHOLINESTERASE glial cell line-derived neurotrophic factor inclined board test basso Beattie and Bresnahan locomotor rating scale functional recovery neuralregeneration
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Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury 被引量:13
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作者 Jian-long Wang Qing-shan Zhang +4 位作者 Kai-di Zhu Jian-feng Sun Ze-peng Zhang Jian-wen Sun Ke-xiang Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第6期958-964,共7页
Hydrogen can relieve tissue-damaging oxidative stress, inflammation and apoptosis. Injection of hydrogen-rich saline is an effective method for transporting molecular hydrogen. We hypothesized that hydrogen-rich salin... Hydrogen can relieve tissue-damaging oxidative stress, inflammation and apoptosis. Injection of hydrogen-rich saline is an effective method for transporting molecular hydrogen. We hypothesized that hydrogen-rich saline would promote the repair of spinal cord injury induced by Allen's method in rats. At 0.5, 1, 2, 4, 8, 12 and 24 hours after injury, then once daily for 2 weeks, 0.25 mL/kg hydrogen-rich saline was infused into the subarachnoid space through a catheter. Results at 24 hours, 48 hours, 1 week and 2 weeks after injury showed that hydrogen-rich saline markedly reduced cell death, inflammatory cell infiltration, serum malondialdehyde content, and caspa se-3 immunoreactivity, elevated serum superoxide dismutase activity and calcitonin gene-related peptide immunoreactivity, and improved motor function in the hindlimb. The present study confirms that hydrogen-rich saline injected within 2 weeks of injury effectively contributes to the repair of spinal cord injury in the acute stage. 展开更多
关键词 nerve regeneration spinal cord injury hydrogen-rich saline reactive oxygen species physiological saline oxidative stress basso Beattie and Bresnahan score MALONDIALDEHYDE SUPEROXIDEDISMUTASE calcitonin gene-related peptide caspase-3 neural regeneration
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Endothelial progenitor cell-conditioned medium promotes angiogenesis and is neuroprotective after spinal cord injury 被引量:11
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作者 Tao Wang Xiao Fang Zong-Sheng Yin 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第5期887-895,共9页
Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progeni... Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progenitor cell-conditioned medium might have therapeutic effectiveness for the treatment of spinal cord injury using both in vitro and in vivo experiments. After primary culture of bone marrow-derived macrophages, lipopolysaccharide stimulation was used to classically activate macrophages to their proinflammatory phenotype. These cells were then treated with endothelial progenitor cell-conditioned medium or control medium. Polymerase chain reaction was used to determine mR NA expression levels of related inflammatory factors. Afterwards, primary cultures of rat spinal cord neuronal cells were prepared and treated with H2O2and either endothelial progenitor cell-conditioned medium or control medium. Hoechst 33258 and propidium iodide staining were used to calculate the proportion of neurons undergoing apoptosis. Aortic ring assay was performed to assess the effect of endothelial progenitor cell-conditioned medium on angiogenesis. Compared with control medium, endothelial progenitor cell-conditioned medium mitigated the macrophage inflammatory response at the spinal cord injury site, suppressed apoptosis, and promoted angiogenesis. Next, we used a rat model of spinal cord injury to examine the effects of the endothelial progenitor cell-conditioned medium in vivo. The rats were randomly administered intraperitoneal injection of PBS, control medium or endothelial progenitor cell-conditioned medium, once a day, for 6 consecutive weeks. Immunohistochemistry was used to observe neuronal morphology. Terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was performed to detect the proportion of apoptotic neurons in the gray matter. The Basso, Beattie and Bresnahan Locomotor Rating Scale was used to evaluate the recovery of motor function of the bilateral hind limbs after spinal cord injury. Co 展开更多
关键词 nerve regeneration endothelial progenitor cells conditioned medium spinal cord injury inflammation classical macrophages ANGIOGENESIS NEUROPROTECTION alternatively activated macrophages basso Beattie and Bresnahan score neural regeneration
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Serum and cerebrospinal fluid tau protein level as biomarkers for evaluating acute spinal cord injury severity and motor function outcome 被引量:9
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作者 Ying Tang Hong-Liang Liu +6 位作者 Ling-Xia Min Hao-Shi Yuan Lei Guo Peng-Bo Han Yu-Xin Lu Jian-Feng Zhong Dong-Lin Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第5期896-902,共7页
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
关键词 nerve REGENERATION spinal cord INJURY tau INJURY SEVERITY OUTCOME cerebrospinal fluid SERUM biomarker basso Beattie and Bresnahan LOCOMOTOR rating scale neural REGENERATION
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Effects of decompression joint Governor Vessel electro-acupuncture on rats with acute upper cervical spinal cord injury 被引量:8
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作者 Yan-Lei Wang Ying-Na Qi +5 位作者 Wei Wang Chun-Ke Dong Ping Yi Feng Yang Xiang-Sheng Tang Ming-Sheng Tan 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第7期1241-1246,共6页
Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatme... Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury.Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord.In this study,Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury.The rat models were established by inserting a balloon catheter into the atlanto-occipital space.The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression.Electroacupuncture was conducted at the acupoints Dazhui(GV14) and Baihui(GV 20)(2 Hz,15 minutes) once a day for 14 consecutive days.Compared with decompression alone,hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture.However,the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours.Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone.These findings indicate that compared with decompression alone,Governor Vessel electroacupuncture combined with delayed decompression(48 hours) is more effective in the treatment of upper cervical spinal cord injury.Governor Vessel electroacupuncture combined with early decompression(12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury.Nevertheless,further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone. 展开更多
关键词 nerve regeneration acute spinal cord injury decompression Governor Vessel electroacupuncture platelet-activating factor apoptosis methylprednisolone caspase family upper cervical spine animal model basso Beattie and Bresnahan locomotor scale neural regeneration
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Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury 被引量:6
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作者 Norio Tanabe Tomoharu Kuboyama Chihiro Tohda 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第11期1961-1967,共7页
In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully imp... In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness is not sufficient. We previously found a new effective compound for spinal cord injury, matrine, which induced axonal growth and functional recovery in acute spinal cord injury mice via direct activation of extracellular heat shock protein 90. Although our previous study clarified that matrine was an activator of extracellular heat shock protein 90, the potential of matrine for spinal cord injury in chronic phase has not been sufficiently evaluated. Thus, this study aimed to investigate whether matrine ameliorates chronic spinal cord injury in mice. Once daily intragastric administration of matrine(100 μmol/kg per day) to spinal cord injury mice were starte at 28 days after injury, and continued for 154 days. Continuous mat rine treatment improved hindlimb motor function in chronic spinal cord injury mice. In injured spinal cords of the matrine-treated mice, the density of neurofilament-H-positive axons was increased. Moreover, matrine treatment increased the density of bassoon-positive presynapses in contact with choline acetyltransferase-positive motor neurons in the lumbar spinal cord. These findings suggest that matrine promotes remodeling and reconnection of neural circuits to regulate hindlimb movement. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama(approval No. A2013 INM-1 and A2016 INM-3) on May 7, 2013 and May 17, 2016, respectively. 展开更多
关键词 MATRINE chronic spinal cord injury axonal growth SYNAPTOGENESIS HINDLIMB LOCOMOTOR presynapse immunohistochemistry basso MOUSE Scale Body Support Score SOPHORA flavescens
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神经前体细胞巢蛋白在大鼠脊髓损伤后的表达 被引量:6
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作者 李俊岑 丁培培 +3 位作者 刘姿辰 张剑 梁楠 张晓 《中国康复医学杂志》 CAS CSCD 北大核心 2010年第9期833-837,共5页
目的:探讨成年大鼠脊髓损伤后损伤(SCI)区局部巢蛋白(nestin)的表达及意义。方法:应用Allen法建立大鼠SCI模型,行为学评分采用BBB评分,用病理学和免疫组织化学方法检测脊髓在不同时段的病理改变和nestin的表达变化。结果:伤后第1天,脊... 目的:探讨成年大鼠脊髓损伤后损伤(SCI)区局部巢蛋白(nestin)的表达及意义。方法:应用Allen法建立大鼠SCI模型,行为学评分采用BBB评分,用病理学和免疫组织化学方法检测脊髓在不同时段的病理改变和nestin的表达变化。结果:伤后第1天,脊髓实质灶状出血,小血管栓塞,部分神经细胞细胞核碎裂,见损伤区附近、软脊髓膜下的白质和脊髓中央管区有nestin表达,BBB评分低,随后增加,1—2周恢复幅度加大。第3天后损伤灶出现大量胶质细胞,损伤组织液化。第5天后液化灶逐渐扩大,出血减少,阳性神经元和阳性反应的平均积分光密度值达到高峰(P<0.05)。第7天后神经细胞退行性变更为严重,部分神经细胞崩解仅留其轮廓,胶质细胞增生明显。2周后出血已基本吸收,以损伤处为中心,囊腔开始形成,nestin表达明显下调(P<0.05)。结论:脊髓损伤可诱导损伤区周围短暂的nestin阳性表达,nestin可能在脊髓损伤后的再生与修复中起重要作用。 展开更多
关键词 脊髓损伤 巢蛋白 Allen撞击器 basso Beattie Bresnahan运动功能评分
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Local injection of bone morphogenetic protein 7 promotes neuronal regeneration and motor function recovery after acute spinal cord injury 被引量:6
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作者 Chen Chen Guang-Chao Bai +2 位作者 Hong-Liang Jin Kun Lei Kuan-Xin Li 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第6期1054-1060,共7页
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
关键词 nerve regeneration BEHAVIOR basso Beattie Bresnahan scale score motor evoked potential wave Nissl staining NEURONS glial cells neurofilament protein 200 glial fibrillary acidic protein neural regeneration
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Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons 被引量:5
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作者 Duo Zhang Di Zhu +4 位作者 Fang Wang Ji-Chao Zhu Xu Zhai Yuan Yuan Chen-Xi Li 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第6期1120-1132,共13页
Objective:An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury,and that regulating autophagy can enhance recovery from spinal cord injury.However,th... Objective:An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury,and that regulating autophagy can enhance recovery from spinal cord injury.However,the effect of regulating autophagy and whether autophagy is detrimental or beneficial after spinal cord injury remain unclear.Therefore,in this study we evaluated the effects of autophagy regulation on spinal cord injury in rats by direct and indirect comparison,in an effort to provide a basis for further research.Data source:Relevant literature published from inception to February 1,2018 were included by searching Wanfang,CNKI,Web of Science,MEDLINE(OvidSP),PubMed and Google Scholar in English and Chinese.The keywords included"autophagy","spinal cord injury",and"rat".Data selection:The literature included in vivo experimental studies on autophagy regulation in the treatment of spinal cord injury(including intervention pre-and post-spinal cord injury).Meta-analyses were conducted at different time points to compare the therapeutic effects of promoting or inhibiting autophagy,and subgroup analyses were also conducted.Outcome measure:Basso,Beattie,and Bresnahan scores.Results:Of the 622 studies,33 studies of median quality were included in the analyses.Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=1.80,95%CI:0.81-2.79,P=0.0004),3 days(MD=0.92,95%CI:0.72-1.13,P<0.00001),1 week(MD=2.39,95%CI:1.85-2.92,P<0.00001),2 weeks(MD=3.26,95%CI:2.40-4.13,P<0.00001),3 weeks(MD=3.13,95%CI:2.51-3.75,P<0.00001)and 4 weeks(MD=3.18,95%CI:2.43-3.92,P<0.00001)after spinal cord injury with upregulation of autophagy compared with the control group(drug solvent control,such as saline group).Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=6.48,95%CI:5.83-7.13,P<0.00001),2 weeks(MD=2.43,95%CI:0.79-4.07,P=0.004),3 weeks(MD=2.96,95%CI:0.09-5.84,P=0.04)and 4 weeks(MD=4.41,95%CI:1.08-7.75,P=0.01)after spinal cord injury with downregulation of autophagy compared with the control group.Indirect comparison of upr 展开更多
关键词 AUTOPHAGY basso Beattie and Bresnahan SCORES indirect comparison meta-analysis nerve REGENERATION neural REGENERATION NEUROLOGICAL function rat models regulation spinal CORD injury strategy analysis
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Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries:a meta-analysis 被引量:4
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作者 Kai Qian Tuo-Ye Xu +7 位作者 Xi Wang Tao Ma Kai-Xin Zhang Kun Yang Teng-Da Qian Jing Shi Li-Xin Li Zheng Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第4期748-758,共11页
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 tr 展开更多
关键词 basso Beattie and Bresnahan locomotor rating scale CELL TRANSPLANTATION META-ANALYSIS motor functional recovery NEURAL regeneration NEURAL stem CELL NEURAL stem CELL TRANSPLANTATION rat model SPINAL CONTUSION SPINAL cord injury
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A progressive compression model of thoracic spinal cord injury in mice: function assessment and pathological changes in spinal cord 被引量:3
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作者 Guo-dong Sun Yan Chen +3 位作者 Zhi-gang Zhou Shu-xian Yang Cheng Zhong Zhi-zhong Li 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第8期1365-1374,共10页
Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few... Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups: in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal(0.2 mm) post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury. 展开更多
关键词 nerve regeneration progressive spinal cord compression injury pathological changes basso Mouse Scale scores gait motor evokedpotentials ASTROCYTES MICROGLIA motor neurons hindlimb dysfunction neural regeneration
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Globose basal cells for spinal cord regeneration 被引量:3
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作者 Durai Murugan Muniswami Indirani Kanakasabapathy George Tharion 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第11期1895-1904,共10页
Spinal cord injury (SCI) is a devastating condition with loss of motor and sensory functions below the injury level. Cell based therapies are experimented in pre-clinical studies around the world. Neural stem cells ... Spinal cord injury (SCI) is a devastating condition with loss of motor and sensory functions below the injury level. Cell based therapies are experimented in pre-clinical studies around the world. Neural stem cells are located intra-craniafly in subventricular zone and hippocampus which are highly invasive sourc- es. The olfactory epithelium is a neurogenic tissue where neurogenesis takes place throughout the adult life by a population of stem/progenitor cells. Easily accessible olfactory neuroepithelial stem/progenitor cells are an attractive cell source for transplantation in SCI. Globose basal cells (GBCs) were isolated from rat olfactory epithelium, characterized by flow cytometry and immunohistochemically. These ceils were further studied for neurosphere formation and neuronal induction. T10 laminectomy was done to create drop-weight SCI in rats. On the 9th day following SCI, 5 × 105 cells were transplanted into injured rat spinal cord. The outcome of transplantation was assessed by the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, motor evoked potential and histological observation. GBCs expressed neural stem cell markers nestin, SOX2, NCAM and also mesenchymal stem cell markers (CD29, CD54, CD90, CD73, CD105). These cells formed neurosphere, a culture characteristics of NSCs and on induction, differentiated cells expressed neuronal markers ~III tubulin, microtubule-associated protein 2, neuronal nuclei, and neurofilament. GBCs transplanted rats exhibited hindlimb motor recovery as confirmed by BBB score and gastrocnemius muscle electromyography amplitude was increased compared to controls. Green fluorescent protein labelled GBCs survived around the injury epicenter and differentiated into βⅢ tubulin-immunoreactive neuron-like cells. GBCs could be an alternative to NSCs from an accessible source for autologous neurotransplantation after SCI without ethical issues. 展开更多
关键词 nerve regeneration the basso Beattie and Bresnahan (BBB) locomotor scale score BBB score EMG globose basal cells spinal cord injury TRANSPLANTATION neural stem cell marker neural regeneration
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Neuroprotective effects of Alda-1 mitigate spinal cord injury in mice:involvement of Alda-1-induced ALDH2 activation-mediated suppression of reactive aldehyde mechanisms 被引量:4
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作者 Mushfiquddin Khan Fei Qiao +4 位作者 Pavan Kumar S.M.Touhidul Islam Avtar K.Singh Jeseong Won Inderjit Singh 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第1期185-193,共9页
Spinal cord injury(SCI)is associated with high production and excessive accumulation of pathological 4-hydroxy-trans-2-nonenal(4-HNE),a reactive aldehyde,formed by SCI-induced metabolic dysregulation of membrane lipid... Spinal cord injury(SCI)is associated with high production and excessive accumulation of pathological 4-hydroxy-trans-2-nonenal(4-HNE),a reactive aldehyde,formed by SCI-induced metabolic dysregulation of membrane lipids.Reactive aldehyde load causes redox alteration,neuroinflammation,neurodegeneration,pain-like behaviors,and locomotion deficits.Pharmacological scavenging of reactive aldehydes results in limited improved motor and sensory functions.In this study,we targeted the activity of mitochondrial enzyme aldehyde dehydrogenase 2(ALDH2)to detoxify 4-HNE for accelerated functional recovery and improved pain-like behavior in a male mouse model of contusion SCI.N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide(Alda-1),a selective activator of ALDH2,was used as a therapeutic tool to suppress the 4-HNE load.SCI was induced by an impactor at the T9–10 vertebral level.Injured animals were initially treated with Alda-1 at 2 hours after injury,followed by once-daily treatment with Alda-1 for 30 consecutive days.Locomotor function was evaluated by the Basso Mouse Scale,and pain-like behaviors were assessed by mechanical allodynia and thermal algesia.ALDH2 activity was measured by enzymatic assay.4-HNE protein adducts and enzyme/protein expression levels were determined by western blot analysis and histology/immunohistochemistry.SCI resulted in a sustained and prolonged overload of 4-HNE,which parallels with the decreased activity of ALDH2 and low functional recovery.Alda-1 treatment of SCI decreased 4-HNE load and enhanced the activity of ALDH2 in both the acute and the chronic phases of SCI.Furthermore,the treatment with Alda-1 reduced neuroinflammation,oxidative stress,and neuronal loss and increased adenosine 5′-triphosphate levels stimulated the neurorepair process and improved locomotor and sensory functions.Conclusively,the results provide evidence that enhancing the ALDH2 activity by Alda-1 treatment of SCI mice suppresses the 4-HNE load that attenuates neuroinflammation and neurodegeneration,promotes the 展开更多
关键词 4-hydroxy-trans-2-nonenal Alda-1 ALDH2 basso Mouse Scale score functional recovery mitochondrial function NEUROINFLAMMATION neuroprotection pain spinal cord injury
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Assessment of hindlimb motor recovery affer severe thoracic spinal cord injury in rats: classification of CatWalk XT■ gait analysis parameters 被引量:1
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作者 Guoli Zheng Hao Zhang +6 位作者 Mohamed Tail Hao Wang Johannes Walter Thomas Skutella Andreas Unterberg Klaus Zweckberger Alexander Younsi 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第5期1084-1089,共6页
Assessment of locomotion recovery in preclinical studies of experimental spinal cord injury remains challenging. We studied the CatWalk XT■gait analysis for evaluating hindlimb functional recovery in a widely used an... Assessment of locomotion recovery in preclinical studies of experimental spinal cord injury remains challenging. We studied the CatWalk XT■gait analysis for evaluating hindlimb functional recovery in a widely used and clinically relevant thoracic contusion/compression spinal cord injury model in rats. Rats were randomly assigned to either a T9 spinal cord injury or sham laminectomy. Locomotion recovery was assessed using the Basso, Beattie, and Bresnahan open field rating scale and the CatWalk XT■gait analysis. To determine the potential bias from weight changes, corrected hindlimb(H) values(divided by the unaffected forelimb(F) values) were calculated. Six weeks after injury, cyst formation, astrogliosis, and the deposition of chondroitin sulfate glycosaminoglycans were assessed by immunohistochemistry staining. Compared with the baseline, a significant spontaneous recovery could be observed in the CatWalk XT■parameters max intensity, mean intensity, max intensity at%, and max contact mean intensity from 4 weeks after injury onwards. Of note, corrected values(H/F) of CatWalk XT■parameters showed a significantly less vulnerability to the weight changes than absolute values, specifically in static parameters. The corrected CatWalk XT■parameters were positively correlated with the Basso, Beattie, and Bresnahan rating scale scores, cyst formation, the immunointensity of astrogliosis and chondroitin sulfate glycosaminoglycan deposition. The CatWalk XT■gait analysis and especially its static parameters, therefore, seem to be highly useful in assessing spontaneous recovery of hindlimb function after severe thoracic spinal cord injury. Because many CatWalk XT■parameters of the hindlimbs seem to be affected by body weight changes, using their corrected values might be a valuable option to improve this dependency. 展开更多
关键词 basso Beattie and Bresnahan rating scale behavioral assessment CatWalk XT■gait analysis contusive and compressive injury hindlimb motor function histological changes spinal cord injury spontaneous recovery THORACIC weight
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施万细胞治疗大鼠创伤性脊髓损伤的Meta分析 被引量:4
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作者 卢腾 刘超 +3 位作者 董军 陆梦 康健 贺西京 《中国循证医学杂志》 CSCD 2015年第6期705-712,共8页
目的系统评价施万细胞(SCs)或激活态施万细胞(ASCs)移植对创伤性脊髓损伤(TSCI)大鼠运动功能的影响和安全性。方法计算机检索Pub Med、EMbase、The Cochrane Library(2014年第12期)、CBM、EMbase、CNKI、Wan Fang Data和VIP数据库,收集... 目的系统评价施万细胞(SCs)或激活态施万细胞(ASCs)移植对创伤性脊髓损伤(TSCI)大鼠运动功能的影响和安全性。方法计算机检索Pub Med、EMbase、The Cochrane Library(2014年第12期)、CBM、EMbase、CNKI、Wan Fang Data和VIP数据库,收集有关SCs或ASCs移植治疗大鼠TSCI的随机对照实验(RCT),检索时限均为建库至2014年12月。由2位研究者独立按纳入与排除标准筛选文献、提取资料和评价纳入研究的偏倚风险后,采用Rev Man 5.3软件进行Meta分析。结果最终纳入14个RCT,共计510只大鼠。Meta分析结果显示:单用SCs或ASCs移植术后4周[SMD=2.31,95%CI(1.48,3.13),P<0.000 01]、8周[SMD=3.93,95%CI(3.06,4.81),P<0.000 01]、12周[SMD=6.15,95%CI(4.30,8.00),P<0.000 01]的BBB评分优于对照组。SCs或ASCs联合其他治疗方法移植术后4周[SMD=1.06,95%CI(0.44,1.68),P=0.000 8]、8周[SMD=2.26,95%CI(1.57,2.96),P<0.000 01]、12周[SMD=1.49,95%CI(0.72,2.25),P<0.000 01]的BBB评分优于单用其他治疗方法。ASCs移植组在术后4周[SMD=4.31,95%CI(3.50,5.13),P<0.000 01]、12周[SMD=5.44,95%CI(3.99,6.89),P<0.000 01]的BBB评分优于SCs移植组。移植组和对照组死亡率的差异无统计学意义。结论当前证据表明,SCs和ASCs移植可提高TSCI大鼠运动功能,且安全性高。ASCs较SCs具有更强的修复能力。受纳入研究质量限制,上述结论尚需开展更多大样本、高质量的RCT来加以验证。 展开更多
关键词 脊髓损伤 施万细胞 移植 BBB评分 大鼠 META分析
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神经干细胞与许旺细胞共移植于大鼠损伤脊髓 被引量:3
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作者 夏雷 万虹 +3 位作者 历俊华 郝淑煜 杨飞 王身国 《中华神经外科杂志》 CSCD 北大核心 2008年第10期740-743,共4页
目的观察神经干细胞与许旺细胞共移植于大鼠半横断脊髓损伤处神经干细胞的迁移、存活、分化及对损伤脊髓的修复作用。方法绿色荧光蛋白(GFP)标记脊髓神经干细胞后与许旺细胞共移植于大鼠半横断脊髓损伤处,免疫荧光染色和电镜技术分... 目的观察神经干细胞与许旺细胞共移植于大鼠半横断脊髓损伤处神经干细胞的迁移、存活、分化及对损伤脊髓的修复作用。方法绿色荧光蛋白(GFP)标记脊髓神经干细胞后与许旺细胞共移植于大鼠半横断脊髓损伤处,免疫荧光染色和电镜技术分别观察神经干细胞的迁移、存活、分化及新生的髓鞘。皮层运动诱发电位(CMEPs)及BBB评分分别检测大鼠运动功能的恢复。结果在神经干细胞与许旺细胞共移植组,损伤脊髓的头端、尾端及对侧可见明显的GFP阳性细胞及GaLC/GFP、GFAP/GFP、NSE/GFP、SYN/GFP双阳性细胞,电镜下新生的髓鞘最多,CMEPs恢复百分率和振幅明显高于其他两组,但BBB评分与神经干细胞单移植组差异无统计学意义。结论神经干细胞和许旺细胞体内共移植可促进神经干细胞的迁移、存活、分化及脊髓运动功能的恢复。 展开更多
关键词 神经干细胞 许旺细胞 绿色荧光蛋白 运动诱发电位 BBB评分
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Neurofilament 200 expression in a rat model of complete spinal cord injury following growth-associated protein-43 treatment
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作者 Yanping Duan Dongkui Zhang +5 位作者 Yingchun Ba Yun Yuan Jun Sun Dengli Fu Ran Zhang Jinde Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第11期827-831,共5页
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 s 展开更多
关键词 spinal cord injury growth-associated protein-43 neurofilament 200 basso Beattie and Bresnahan locomotor rating scale
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注射硫酸软骨素酶对大鼠脊髓损伤后腓肠肌乙酰胆碱酯酶的变化及运动功能的影响 被引量:1
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作者 李洪鹏 白旭东 +2 位作者 高杰 巴方 刘宁 《中国康复理论与实践》 CSCD 北大核心 2012年第3期219-221,共3页
目的探讨注射硫酸软骨素酶ABC对成年大鼠脊髓损伤后不同时期后肢运动功能的恢复及腓肠肌运动终板内乙酰胆碱酯酶的影响。方法 10周龄Wistar雄性大鼠40只,采用脊髓半横断法制作模型,健侧作为对照组(A组),患侧随机分为单纯脊髓损伤组(... 目的探讨注射硫酸软骨素酶ABC对成年大鼠脊髓损伤后不同时期后肢运动功能的恢复及腓肠肌运动终板内乙酰胆碱酯酶的影响。方法 10周龄Wistar雄性大鼠40只,采用脊髓半横断法制作模型,健侧作为对照组(A组),患侧随机分为单纯脊髓损伤组(B组)及术后注射硫酸软骨素酶ABC组(C组)。术后采用BBB评分法进行行为学观察,分别于损伤后3 d、7 d、14 d和28d各选取5只大鼠,酶化学染色法检测腓肠肌中乙酰胆碱酯酶(AChE)的表达。结果 C组在术后14~28 d BBB评分高于B组(P〈0.05);B组和C组与A组相比,腓肠肌AChE活性均降低,但C组于术后14~28 d AchE活性高于B组(P〈0.05)。结论大鼠脊髓损伤后注射硫酸软骨素酶可以提高AChE的活性,并可提高大鼠患肢的运动功能。 展开更多
关键词 脊髓损伤 硫酸软骨素酶 BBB评分 乙酰胆碱酯酶 大鼠
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E DISTRIBUZIONE DELLE TANE DI TASSO Meles meles NEL BASSO LODIGIANO
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作者 GIANCARLO QUADRELLI 《Natural Disaster Reduction in China》 1992年第1期429-431,共3页
Nel corso del 1991 è stato effettuato un censimento delle tane di Tasso Meles melesin un’area molto antropizzata della Pianura Padana posta alla conflaenza del flume Lambro nel flumePo, estesa per 103 Km^2. Si s... Nel corso del 1991 è stato effettuato un censimento delle tane di Tasso Meles melesin un’area molto antropizzata della Pianura Padana posta alla conflaenza del flume Lambro nel flumePo, estesa per 103 Km^2. Si sono individuate 24 tane (0,2 Km^2). Density and distribution of Badger’s setts (Meles meles) in the Lower Lodigiano (NorthernItaly). A census of the Badger’s setts (Meles meles) was carried out in 1991 in a densely inhabited areaof the Po Plain, near the mouth of the river Lambro into the Po. In the study area (extended for103 Km^2) 24 setts have been found (0,2 Km^2). 展开更多
关键词 PI E DISTRIBUZIONE DELLE TANE DI TASSO Meles meles NEL basso LODIGIANO
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bFGF对大鼠急性脊髓损伤组织内质网应激(ERS)信号通路相关蛋白CHOP、Caspase12表达的影响
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作者 葛小刚 蔡旗旗 +1 位作者 牟财国 蔡杨阳 《中国现代医生》 2021年第11期36-39,F0003,共5页
目的探讨碱性成纤维细胞因子(bFGF)对大鼠急性脊髓损伤内质网应激(ERS)信号通路相关蛋白CHOP、Caspase12表达的影响。方法选取SD大鼠90只分为三组,每组各30只。Sham组为假手术组;SCI组采用HI-0400脊髓打击器制备急性脊髓损伤模型;bFGF组... 目的探讨碱性成纤维细胞因子(bFGF)对大鼠急性脊髓损伤内质网应激(ERS)信号通路相关蛋白CHOP、Caspase12表达的影响。方法选取SD大鼠90只分为三组,每组各30只。Sham组为假手术组;SCI组采用HI-0400脊髓打击器制备急性脊髓损伤模型;bFGF组在SCI组基础上予bFGF蛛网膜下隙给药,评估损伤后不同时点后肢运动功能评分、脊髓细胞凋亡及脊髓组织CHOP、Caspase12表达情况。结果bFGF组损伤后21 d、28 d的BBB评分分别为(12.48±0.42)分、(13.53±0.47)分,均高于SCI组,差异有统计学意义(t=7.533、9.963,P<0.05)。bFGF组损伤后1 d、3 d、7 d细胞凋亡分别为(7.13±0.45)%、(12.42±1.21)%、(10.31±1.27)%,均低于SCI组,差异有统计学意义(t=4.684、8.945、6.507,P<0.05)。bFGF组CHOP及Caspase12表达分别为(7.66±0.74)分、(7.52±0.87)分,显著低于SCI组,差异有统计学意义(t=12.348、8.653,P<0.05)。结论bFGF可通过抑制ERS相关蛋白CHOP、Caspase12的表达,对大鼠急性脊髓损伤起保护作用。 展开更多
关键词 碱性成纤维细胞因子 内质网应激 大鼠急性脊髓损伤 保护作用 脊髓损伤评分 白细胞介素1-β转换酶家族12
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