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The therapeutic potential of targeting exchange protein directly activated by cyclic adenosine 3',5'-monophosphate(Epac)for central nervous system trauma 认领
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作者 Alba Guijarro-Belmar Dominik Mateusz Domanski +2 位作者 Xuenong Bo Derryck Shewan Wenlong Huang 《中国神经再生研究:英文版》 SCIE CAS 2021年第3期460-469,共10页
Millions of people worldwide are affected by traumatic spinal cord injury,which usually results in permanent sensorimotor disability.Damage to the spinal cord leads to a series of detrimental events including ischaemi... Millions of people worldwide are affected by traumatic spinal cord injury,which usually results in permanent sensorimotor disability.Damage to the spinal cord leads to a series of detrimental events including ischaemia,haemorrhage and neuroinflammation,which over time result in further neural tissue loss.Eventually,at chronic stages of traumatic spinal cord injury,the formation of a glial scar,cystic cavitation and the presence of numerous inhibitory molecules act as physical and chemical barriers to axonal regrowth.This is further hindered by a lack of intrinsic regrowth ability of adult neurons in the central nervous system.The intracellular signalling molecule,cyclic adenosine 3′,5′-monophosphate(cAMP),is known to play many important roles in the central nervous system,and elevating its levels as shown to improve axonal regeneration outcomes following traumatic spinal cord injury in animal models.However,therapies directly targeting cAMP have not found their way into the clinic,as cAMP is ubiquitously present in all cell types and its manipulation may have additional deleterious effects.A downstream effector of cAMP,exchange protein directly activated by cAMP 2(Epac2),is mainly expressed in the adult central nervous system,and its activation has been shown to mediate the positive effects of cAMP on axonal guidance and regeneration.Recently,using ex vivo modelling of traumatic spinal cord injury,Epac2 activation was found to profoundly modulate the post-lesion environment,such as decreasing the activation of astrocytes and microglia.Pilot data with Epac2 activation also suggested functional improvement assessed by in vivo models of traumatic spinal cord injury.Therefore,targeting Epac2 in traumatic spinal cord injury could represent a novel strategy in traumatic spinal cord injury repair,and future work is needed to fully establish its therapeutic potential. 展开更多
关键词 ASTROCYTES axonal regeneration cAMP central nervous system regeneration Epac glial scar microglia NEUROINFLAMMATION neurons spinal cord spinal cord injury traumatic spinal cord injury
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Effects of durotomy versus myelotomy in the repair of spinal cord injury 认领
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作者 Dionne Telemacque Feng-Zhao Zhu +7 位作者 Zheng-Wei Ren Kai-Fang Chen Deepak Drepaul Sheng Yao Fan Yang Yan-Zheng Qu Ting-Fang Sun Xiao-Dong Guo 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第10期1814-1820,共7页
Current management for spinal cord injury aims to reduce secondary damage and recover sensation and movement.Acute spinal cord injury is often accompanied by spinal cord compartment syndrome.Decompression by durotomy ... Current management for spinal cord injury aims to reduce secondary damage and recover sensation and movement.Acute spinal cord injury is often accompanied by spinal cord compartment syndrome.Decompression by durotomy and/or myelotomy attempts to relieve secondary damage by completelyrelieving the compression of the spinal cord,removing the necrotic tissue,decreasing edema,reducing hemorrhage,and improving blood circulation in the spinal cord.However,it is controversial whether durotomy and/or myelotomy after spinal cord injury are beneficial to neurological recovery.This review compares the clinical effects of durotomy with those of myelotomy in the treatment of spinal cord injury.We found that durotomy has been performed more than myelotomy in the clinic,and that durotomy may be safer and more effective than myelotomy.Durotomy performed in humans had positive effects on neurological function in 92.3% of studies in this review,while durotomy in animals had positive effects on neurological function in 83.3% of studies.Myelotomy procedures were effective in 80% of animal studies,but only one clinical study of myelotomy has reported positive results,of motor and sensory improvement,in humans.However,a number of new animal studies have reported that durotomy and myelotomy are ineffective for spinal cord injury.More clinical data,in the form of a randomized controlled study,are needed to understand the effectiveness of durotomy and myelotomy. 展开更多
关键词 decompression durotomy INTRASPINAL PRESSURE LAMINECTOMY MYELOTOMY neurological recovery SPINAL CORD compartment syndrome SPINAL CORD injury SPINAL CORD interstitial PRESSURE
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脊髓脱细胞支架对大鼠脊髓缺损修复的影响 认领
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作者 朱君毅 张宜家 +6 位作者 杜胜虎 余方正 卢颖枫 李培丰 王志斌 梅劲 王健 《解剖学报》 CAS CSCD 北大核心 2020年第4期502-506,共5页
目的用振荡法制备脊髓脱细胞支架修复同种异体大鼠脊髓缺损,观察术后大鼠行为学及组织再生情况。为脊髓缺损后修复提供新的研究思路。方法将30只SD大鼠脊髓分别用50 ml 3%聚乙二醇辛基苯基醚(Triton X-100)和2%脱氧胆酸钠溶液在摇床上... 目的用振荡法制备脊髓脱细胞支架修复同种异体大鼠脊髓缺损,观察术后大鼠行为学及组织再生情况。为脊髓缺损后修复提供新的研究思路。方法将30只SD大鼠脊髓分别用50 ml 3%聚乙二醇辛基苯基醚(Triton X-100)和2%脱氧胆酸钠溶液在摇床上做振荡处理,对比处理前后细胞残留情况及组织的空间结构,了解支架本身的组织构成。将90只SD大鼠随机分成空白对照组、单纯脊髓缺损组和支架移植组。切除单纯脊髓缺损组和支架移植组大鼠腰椎9~10节段,移植脱细胞支架至支架移植组大鼠。术后饲养12周,期间进行行为学评分观察,分别在4、8及12周时取大鼠损伤部位的脊髓进行HE染色及神经再生相关蛋白免疫荧光检测。结果通过HE、Masson、甲苯胺蓝染色显示,脱细胞处理后的脊髓脱细胞支架上神经细胞及轴突彻底清除,保留了脊髓细胞外基质。扫描电子显微镜观察发现,支架保留一定多孔网状支架结构。脱细胞支架在体实验中,Basso-Beattie-Bresnahan(BBB)评分显示,移植有脱细胞支架的大鼠后肢运动功能恢复优于单纯损伤组大鼠。组织学HE染色显示,脱细胞支架能够填补缺损的脊髓节段,加快损伤脊髓的修复过程。免疫荧光显示,支架移植组大鼠的损伤部位有一定轴突再生。结论脊髓脱细胞支架保留了细胞外基质并具有一定空间结构,能够一定程度加快脊髓缺损修复,对神经再生具有一定的促进作用。 展开更多
关键词 脊髓再生 脊髓损伤 脱细胞脊髓支架 轴突再生 苏木素-伊红染色 大鼠
抑制miR-429促进ZO-1、Occludin和Claudin-5蛋白表达改善血脊髓屏障通透性的体外实验研究 认领
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作者 孙瑞 于德水 《中国修复重建外科杂志》 CAS CSCD 北大核心 2020年第9期1163-1169,共7页
目的探讨抑制miR-429改善体外血脊髓屏障(blood spinal cord barrier,BSCB)通透性的可行性及机制,为改善脊髓微环境提供新的基因治疗靶点。方法首先,取永生化人脑微血管内皮细胞系(hCMEC/D3),应用miR-429拮抗剂antagomiR-429及其阴性对... 目的探讨抑制miR-429改善体外血脊髓屏障(blood spinal cord barrier,BSCB)通透性的可行性及机制,为改善脊髓微环境提供新的基因治疗靶点。方法首先,取永生化人脑微血管内皮细胞系(hCMEC/D3),应用miR-429拮抗剂antagomiR-429及其阴性对照antagomiR-429-NC进行转染,通过荧光显微镜观察以及实时荧光定量PCR检测miR-429表达,验证antagomiR-429转染效率。然后观察miR-429对体外BSCB通透性的影响。实验分为4组,其中空白对照组(A组)为正常hCMEC/D3细胞、Ha-sc细胞构建BSCB模型,低氧诱导组(B组)、低氧诱导+antagomiR-429-NC组(C组)、低氧诱导+antagomiR-429组(D组)分别采用正常、antagomiR-429-NC转染以及antagomiR-429转染的hCMEC/D3细胞,与Ha-sc细胞构建BSCB模型并低氧处理12 h。通过辣根过氧化物酶(horseradish peroxidase,HRP)通量测定体外BSCB通透性,实时荧光定量PCR、Western blot和免疫荧光染色观测内皮细胞中紧密连接蛋白ZO-1、Occludin、Claudin-5的表达水平。结果荧光显微镜下观察antagomiR-429及antagomiR-429-NC成功转染至hCMEC/D3细胞,转染效率约为90%;实时荧光定量PCR检测antagomiR-429组miR-429相对表达量为0.109±0.013,明显低于antagomiR-429-NC组的0.956±0.004(P<0.05)。HRP通透性测量、实时荧光定量PCR及Western blot检测显示,B、C组HRP通透性明显高于A、D组,ZO-1、Occludin和Claudin-5蛋白及mRNA相对表达量均明显低于A、D组(P<0.05);B、C组间差异无统计学意义(P>0.05),D组尚未达A组水平(P<0.05)。免疫荧光染色观察示D组ZO-1、Occludin和Claudin-5蛋白在细胞膜边界免疫荧光较B、C组增强,但尚未达A组强度。结论通过抑制miR-429表达可促进微血管内皮细胞中ZO-1、Occludin和Claudin-5蛋白表达,进而改善因低氧导致的BSCB通透性增高。 展开更多
关键词 血脊髓屏障 miR-429 脊髓损伤 紧密连接蛋白 脊髓微环境
Changes in neurological and pathological outcomes in a modified rat spinal cord injury model with closed canal 认领
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作者 Xin Sun Xing-Zhen Liu +4 位作者 Jia Wang Hai-Rong Tao Tong Zhu Wen-Jie Jin Kang-Ping Shen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期697-704,共8页
Most animal spinal cord injury models involve a laminectomy,such as the weight drop model or the transection model.However,in clinical practice,many patients undergo spinal cord injury while maintaining a relatively c... Most animal spinal cord injury models involve a laminectomy,such as the weight drop model or the transection model.However,in clinical practice,many patients undergo spinal cord injury while maintaining a relatively complete spinal canal.Thus,open spinal cord injury models often do not simulate real injuries,and few previous studies have investigated whether having a closed spinal canal after a primary spinal cord injury may influence secondary processes.Therefore,we aimed to assess the differences in neurological dysfunction and pathological changes between rat spinal cord injury models with closed and open spinal canals.Sprague-Dawley rats were randomly divided into three groups.In the sham group,the tunnel was expanded only,without inserting a screw into the spinal canal.In the spinal cord injury with open canal group,a screw was inserted into the spinal canal to cause spinal cord injury for 5 minutes,and then the screw was pulled out,leaving a hole in the vertebral plate.In the spinal cord injury with closed canal group,after inserting a screw into the spinal canal for 5 minutes,the screw was pulled out by approximately 1.5 mm and the flat end of the screw remained in the hole in the vertebral plate so that the spinal canal remained closed;this group was the modified model,which used a screw both to compress the spinal cord and to seal the spinal canal.At 7 days post-operation,the Basso-Beattie-Bresnahan scale was used to measure changes in neurological outcomes.Hematoxylin-eosin staining was used to assess histopathology.To evaluate the degree of local secondary hypoxia,immunohistochemical staining and western blot assays were applied to detect the expression of hypoxia-inducible factor 1α(HIF-1α)and vascular endothelial growth factor(VEGF).Compared with the spinal cord injury with open canal group,in the closed canal group the Basso-Beattie-Bresnahan scores were lower,cell morphology was more irregular,the percentage of morphologically normal neurons was lower,the percentages of HIF-1α-and VEGF-immunorea 展开更多
关键词 Basso-Beattie-Bresnahan scores CLOSED SPINAL CANAL HIF-1α hypoxia MODEL nerve regeneration open SPINAL CANAL rat secondary INJURY SPINAL cord INJURY VEGF
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Concurrent Validity of a Virtual Version of Box and Block Test for Patients with Neurological Disorders 认领
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作者 M. Alvarez-Rodríguez E. López-Dolado +4 位作者 M. Salas-Monedero V. Lozano-Berrio S. Ceruelo-Abajo A. Gil-Agudo A. de los Reyes-Guzmán 《神经科学国际期刊(英文)》 2020年第1期79-89,共11页
Background: The Box and Block clinical test is a validated and standardized scale for use in the clinical environment that allows the assessment of rough manipulative dexterity. Proposing virtual methods to carry out ... Background: The Box and Block clinical test is a validated and standardized scale for use in the clinical environment that allows the assessment of rough manipulative dexterity. Proposing virtual methods to carry out these assessments is an attempt to eliminate some of the subjectivity that the test may entail depending on the observer and the way in which the patient gives instructions. Applied to the assessment of skills after neurological pathologies, previous experiences in stroke patients have been found. So, this work was centered on the Spinal Cord Injury. Objective: To present the virtual application of the Box and Block scale, as well as details about its design and development for its manipulation based on Leap Motion Controller. Methodology: The relationship between the results obtained in the actual test and in the virtual application in healthy subjects and, mostly, patients with cervical spinal cord injury is analyzed, obtaining a high correlation index between both tests’ performance. Results: A high correlation index was obtained between both tests performance, the real and virtual version of the Box and Block Test. Conclusion: This virtual test can serve as an element to evaluate in the future the effectiveness of the RehabHand prototype based on virtual reality applications with a therapeutic and a rehabilitative sense that, manipulated from Leap Motion Controller, allow the improvement of the manipulative dexterity in patients with neurological diseases such as spinal cord injury. 展开更多
关键词 BOX and BLOCK TEST Leap Motion Controller Manual DEXTERITY Spinal Cord Injury VIRTUAL REALITY
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文章速递纳米组织工程化脊髓修复脊髓损伤 认领
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作者 周继辉 姚猛 +4 位作者 王岩松 李新志 周游 黄卫 陈文瑶 《中国组织工程研究》 CAS CSCD 北大核心 2021年第10期1550-1554,共5页
背景:应用组织工程修复脊髓损伤是近年来的研究热点,多数研究仍停留在体外实验阶段。目的:将新型胶原纳米纤维膜与神经干细胞复合构建组织工程化脊髓,探寻其修复脊髓损伤的效果。方法:以胶原为原料,应用电子纺丝技术制备纤维平行排列及... 背景:应用组织工程修复脊髓损伤是近年来的研究热点,多数研究仍停留在体外实验阶段。目的:将新型胶原纳米纤维膜与神经干细胞复合构建组织工程化脊髓,探寻其修复脊髓损伤的效果。方法:以胶原为原料,应用电子纺丝技术制备纤维平行排列及交错排列的纳米纤维膜;将新生大鼠脊髓源性神经干细胞分别接种于两种纳米纤维上培养7 d,构建组织工程化脊髓。建立SD大鼠脊髓半横断动物模型,随机分5组干预:空白对照组未植入任何材料;平行组织工程组与交错组织工程组植入对应的组织工程化脊髓,交错组与平行组植入对应排列的纳米纤维膜。术后1-8周进行改良行为学BBB评分;术后8周取术区脊髓组织,进行苏木精-伊红染色与免疫组化染色。实验获得哈尔滨医科大学实验动物福利和伦理管理委员会批准。结果与结论:①平行组织工程组术后各时间点的改良行为学BBB评分均高于其余4组(P <0.05),交错组织工程组、平行组、交错组各时间点的评分高于空白对照组(P <0.05),交错组织工程组术后2-8周的评分高于平行组、交错组(P <0.05),平行组术后1,2周的评分高于交错组(P <0.05);②苏木精-伊红染色显示,空白对照的损伤区域几乎无细胞结构,可见大量瘢痕组织形成;平行组、交错组抑制了瘢痕组织形成,组织修复不明显,邻近组织瘢痕形成,损伤区与周围未建立细胞联系;两组织工程组支架降解区域内有大量细胞成分,局部有较多组织再生,细胞数量较多,细胞沿支架方向分布,彼此相关并与正常组织相连;③免疫组化染色显示,两组织工程组可见神经元细胞;④结果表明,纳米组织工程化脊髓修复脊髓损伤的效果良好,以平行纳米纤维膜构建的组织工程化脊髓修复效果更佳。 展开更多
关键词 脊髓 材料 纳米纤维 脊髓损伤 组织工程 纳米支架 实验
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脊髓损伤组织匀浆通过甲酰基肽受体2促进神经元突起的生长 认领
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作者 张良 刘明永 +6 位作者 刘鹏 薛鑫 陈宗锋 张良民 张健 郭乔楠 赵建华 《中国组织工程研究》 CAS 北大核心 2020年第1期106-111,共6页
背景:前期研究观察到神经干细胞新分化的神经元表达甲酰基肽受体2,并证实甲酰基肽受体2能促进神经干/祖细胞迁移,诱导向神经元分化。脊髓损伤组织中存在甲酰基肽受体2配体,然而不同的配体与甲酰基肽受体2结合可能导致不同、甚至相反的... 背景:前期研究观察到神经干细胞新分化的神经元表达甲酰基肽受体2,并证实甲酰基肽受体2能促进神经干/祖细胞迁移,诱导向神经元分化。脊髓损伤组织中存在甲酰基肽受体2配体,然而不同的配体与甲酰基肽受体2结合可能导致不同、甚至相反的生物学效应。目的:探讨脊髓损伤产生的配体与甲酰基肽受体2作用后对神经元突起生长的影响。方法:采用酶消化法提取胎鼠大脑皮质神经元;制备SD大鼠脊髓损伤模型,提取损伤脊髓组织匀浆。①实验分组1:观察甲酰基肽受体2激活对神经元突起的影响,分组如下:对照组、甲酰基肽受体2阻断剂组(即添加WRW4)、脊髓匀浆组、脊髓匀浆+WRW4组;②实验分组2:观察甲酰基肽受体2激活后AKT和ERK信号通路阻断对神经元突起的影响,分组如下:对照组、AKT和ERK信号通路阻断剂组(即添加Ly294002+PD98059)、脊髓匀浆组、脊髓匀浆+Ly294002+PD98059组。神经元细胞贴壁24 h后,按上述分组处理7 d,免疫荧光染色共聚焦显微镜观察脊髓匀浆激活甲酰基肽受体2对神经元突起的影响;按上述分组处理30 min,Western blotting检测磷酸化蛋白水平;按上述分组处理24 h,Western blotting检测F-actin水平,观察在甲酰基肽受体2特异性阻断剂WRW4存在的情况下,对MAPK和PI3K/Akt通路中关键蛋白磷酸化的影响。结果与结论:①脊髓损伤组织匀浆液能够使神经元突起长度、初级分枝数、分枝节点数显著增加,这种增加效应大部分被甲酰基肽受体2受体特异性阻断剂WRW4阻断;②脊髓损伤组织匀浆液能够使神经元中ERK1/2和Akt的磷酸化增加,这种效应能够被WRW4阻断;③Akt信号通路阻断剂Ly294002和Erk信号通路阻断剂PD98059能够阻断脊髓匀浆的促进作用;④脊髓损伤组织匀浆能够使F-actin表达量明显增加,这种效应能够被甲酰基肽受体2特异性阻断剂WRW4所阻断;⑤这些实验结果说明,脊髓匀浆液能够� 展开更多
关键词 脊髓损伤 脊髓损伤组织匀浆 神经元 甲酰基肽受体 轴突生长 Akt信号通路 Erk信号通路
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ABC efflux transporters at blood-central nervous system barriers and their implications for treating spinal cord disorders 认领
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作者 Liam M.Koehn 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第7期1235-1242,共8页
The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding c... The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding cassette(ABC)transporters has been widely studied regarding efflux of medications at blood-central nervous system barriers.These efflux transporters include P-glycoprotein(abcb1),‘breast cancer resistance protein'(abcg2)and the various‘multidrug resistance-associated proteins'(abccs).Understanding which efflux transporters are present at the blood-spinal cord,blood-cerebrospinal fluid and cerebrospinal fluid-spinal cord barriers is necessary to determine their involvement in limiting drug transfer from blood to the spinal cord tissue.Recent developments in the blood-brain barrier field have shown that barrier systems are dynamic and the profile of barrier defenses can alter due to conditions such as age,disease and environmental challenge.This means that a true understanding of ABC efflux transporter expression and localization should not be one static value but instead a range that represents the complex patient subpopulations that exist.In the present review,the blood-central nervous system barrier literature is discussed with a focus on the impact of ABC efflux transporters on:(i)protecting the spinal cord from adverse effects of systemically directed drugs,and(ii)limiting centrally directed drugs from accessing their active sites within the spinal cord. 展开更多
关键词 ABC transporters ATP-BINDING cassette BCRP blood-brain BARRIER blood-spinal CORD BARRIER efflux MRP P-glycoprotein PGP SPINAL CORD injury
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Epidural Spinal Cord Stimulation Promotes Motor Functional Recovery by Enhancing Oligodendrocyte Survival and Differentiation and by Protecting Myelin after Spinal Cord Injury in Rats 认领
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作者 Gang Li Zhong-Kai Fan +4 位作者 Guang-Fei Gu Zhi-Qiang Jia Qiang-Qiang Zhang Jun-Yu Dai Shi-Sheng He 《神经科学通报:英文版》 SCIE CAS CSCD 2020年第4期372-384,共13页
Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear.Here, we investigated whether ESCS affects oligodendrocyte... Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear.Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI.ESCS also significantly increased the myelinated area at 28days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 20,30-cyclic-nucleotide 30-phosphodiesterase (CNPase,an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rh BMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI,and rh BMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI. 展开更多
关键词 SPINAL CORD injury EPIDURAL SPINAL CORD stimulation OLIGODENDROCYTE Differentiation REMYELINATION
雷公藤内酯醇改善大鼠脊髓损伤后的运动障碍 认领
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作者 马斌祥 何万庆 +1 位作者 周广超 关永林 《中国组织工程研究》 CAS 北大核心 2021年第5期701-706,共6页
背景:继发性脊髓损伤致残率高的主要诱因之一是氧化应激和炎症反应,如何抑制脊髓继发性损伤是目前研究的热点。目的:探讨雷公藤内酯醇对大鼠脊髓损伤后运动功能障碍的改善作用及其可能机制。方法:将48只健康雄性SD大鼠随机分为假手术组... 背景:继发性脊髓损伤致残率高的主要诱因之一是氧化应激和炎症反应,如何抑制脊髓继发性损伤是目前研究的热点。目的:探讨雷公藤内酯醇对大鼠脊髓损伤后运动功能障碍的改善作用及其可能机制。方法:将48只健康雄性SD大鼠随机分为假手术组、脊髓损伤组和雷公藤内酯醇组,每组16只。采用改良的Allen法建立大鼠脊髓损伤模型。雷公藤内酯醇组大鼠行脊髓损伤30 min后腹腔注射雷公藤内酯醇[0.1 mg/(kg·d)],假手术组及脊髓损伤组均经相同途径给予等量含体积分数1%二甲亚砜的生理盐水,连续治疗10 d,假手术组仅行椎板切除不损伤脊髓。于术后第7,14,21,28,35天采用脊髓损伤的行为学评分法评定各组SD大鼠后肢运动功能;于术后第10天收集大鼠的胸脊髓(T8-11),用于组织学检测和蛋白质印迹、实时定量聚合酶链式反应分析。结果与结论:①脊髓损伤组和雷公藤内酯醇组的脊髓损伤的行为学评分随着伤后天数的增加而增加,且雷公藤内酯醇组在受伤后第14,21,28,35天的行为学评分均显著高于脊髓损伤组(P<0.05);②术后10 d切取各组大鼠的胸脊髓(T8-11)组织经苏木精-伊红染色发现,脊髓损伤组大鼠胸脊髓核心区纵切面显示严重水肿、出血和炎性细胞浸润,而这些异常现象均可被雷公藤内酯醇治疗明显减弱(P<0.05);③RTPCR检测发现,与脊髓损伤组相比,雷公藤内酯醇组大鼠脊髓中肿瘤坏死因子α,p-STAT3和p-JAK2 mRNA表达显著降低(P<0.05),且超氧化物歧化酶和过氧化氢酶的mRNA表达水平明显升高(P<0.05);④结果证实,脊髓损伤后腹腔注射雷公藤内酯醇可适度改善运动功能障碍,其作用机制可能与雷公藤内酯醇调控JAK/STAT信号通路的异常活化有关。 展开更多
关键词 脊髓 脊髓损伤 雷公藤内酯醇 运动障碍 抗氧化 炎症 实验 动物 因子
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脊柱损伤患者术前下肢深静脉血栓形成发生现状及影响因素 认领
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作者 李雪 《颈腰痛杂志》 2020年第4期400-404,共5页
目的探讨脊柱损伤患者术前下肢深静脉血栓形成(deep vein thrombosis,DVT)的发生率及其危险因素。方法选取2018年1月-2019年6月本院诊治的脊柱损伤患者216例,术前均行下肢静脉超声检查,记录DVT发生率;收集患者临床资料,采用多因素Logis... 目的探讨脊柱损伤患者术前下肢深静脉血栓形成(deep vein thrombosis,DVT)的发生率及其危险因素。方法选取2018年1月-2019年6月本院诊治的脊柱损伤患者216例,术前均行下肢静脉超声检查,记录DVT发生率;收集患者临床资料,采用多因素Logistic回归分析探讨脊柱损伤患者术前发生下肢DVT的危险因素。结果216例中,术前共40例发生下肢DVT(DVT组),176例未发生下肢DVT(对照组),下肢DVT发生率为18.52%;DVT组合并高血压比率(55.00%)、高脂血症比率(45.00%)、ASIA分级A-B比率(10.00%)、有大血管粥样硬化比率(42.50%)、受伤至超声检查时间≥7 d比率(55.00%)及血清D-二聚体[(6.26±1.25)mg/L]水平均显著高于对照组[19.89%、5.69%、1.73%、20.45%、29.55%、(2.19±1.08)mg/L],红细胞比容[(34.28±5.22)%]显著低于对照组[(36.89±6.16)%](P<0.05),年龄、性别比例、BMI等与对照组差异无统计学意义(P>0.05);多因素Logistic回归分析结果显示,有高脂血症(OR=2.08,95%CI:1.36-3.79,P=0.000)、ASIA分级A-B级(OR=1.27,95%CI:1.12-1.78,P=0.012)、受伤至超声检查时间≥7 d(OR=1.87,95%CI:1.32-3.89,P=0.000)、血清D-二聚体升高(OR=1.55,95%CI:1.13-2.38,P=0.000)是脊柱损伤患者术前发生下肢DVT的危险因素。结论脊柱损伤患者术前下肢DVT发生率较高,合并内科疾病(高脂血症)、脊髓损伤(ASIA分级A-B级)、受伤至超声检查时间(≥7 d)、血清D-二聚体升高可增加其发生风险。 展开更多
关键词 脊柱损伤 脊髓损伤 深静脉血栓形成 下肢
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Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury:a proof of principle study 认领
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作者 Filip Olegovich Fadeev Farid Vagizovich Bashirov +9 位作者 Vahe Arshaluysovich Markosyan Andrey Alexandrovich Izmailov Tatyana Vyacheslavovna Povysheva Mikhail Evgenyevich Sokolov Maxim Sergeevich Kuznetsov Anton Alexandrovich Eremeev Ilnur Ildusovich Salafutdinov Albert Anatolyevich Rizvanov Hyun Joon Lee Rustem Robertovich Islamov 《中国神经再生研究:英文版》 SCIE CAS 2021年第3期550-560,共11页
Despite emerging contemporary biotechnological methods such as gene-and stem cell-based therapy,there are no clinically established therapeutic strategies for neural regeneration after spinal cord injury.Our previous ... Despite emerging contemporary biotechnological methods such as gene-and stem cell-based therapy,there are no clinically established therapeutic strategies for neural regeneration after spinal cord injury.Our previous studies have demonstrated that transplantation of genetically engineered human umbilical cord blood mononuclear cells producing three recombinant therapeutic molecules,including vascular endothelial growth factor(VEGF),glial cell-line derived neurotrophic factor(GDNF),and neural cell adhesion molecule(NCAM)can improve morpho-functional recovery of injured spinal cord in rats and mini-pigs.To investigate the efficacy of human umbilical cord blood mononuclear cells-mediated triple-gene therapy combined with epidural electrical stimulation in the treatment of spinal cord injury,in this study,rats with moderate spinal cord contusion injury were intrathecally infused with human umbilical cord blood mononuclear cells expressing recombinant genes VEGF165,GDNF,NCAM1 at 4 hours after spinal cord injury.Three days after injury,epidural stimulations were given simultaneously above the lesion site at C5(to stimulate the cervical network related to forelimb functions)and below the lesion site at L2(to activate the central pattern generators)every other day for 4 weeks.Rats subjected to the combined treatment showed a limited functional improvement of the knee joint,high preservation of muscle fiber area in tibialis anterior muscle and increased H/M ratio in gastrocnemius muscle 30 days after spinal cord injury.However,beneficial cellular outcomes such as reduced apoptosis and increased sparing of the gray and white matters,and enhanced expression of heat shock and synaptic proteins were found in rats with spinal cord injury subjected to the combined epidural electrical stimulation with gene therapy.This study presents the first proof of principle study of combination of the multisite epidural electrical stimulation with ex vivo triple gene therapy(VEGF,GDNF and NCAM)for treatment of spinal cord injury in rat mode 展开更多
关键词 adenoviral vector epidural electrical stimulation gene therapy glial cell-line derived neurotrophic factor human umbilical cord blood mononuclear cell neural cell adhesion molecule spinal cord injury vascular endothelial growth factor
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文章速递优质护理干预在脊柱骨折合并脊髓损伤手术围术期的应用探讨 认领
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作者 周振 《基层医学论坛》 2020年第30期4328-4329,共2页
目的探讨优质护理干预在脊柱骨折合并脊髓损伤手术围术期的应用价值。方法抽选150例脊柱骨折合并脊髓损伤手术患者,将其平均分成研究组、参照组,前者给予优质护理干预,后者实施常规护理,对比2组患者护理前后日常生活能力及康复情况评分... 目的探讨优质护理干预在脊柱骨折合并脊髓损伤手术围术期的应用价值。方法抽选150例脊柱骨折合并脊髓损伤手术患者,将其平均分成研究组、参照组,前者给予优质护理干预,后者实施常规护理,对比2组患者护理前后日常生活能力及康复情况评分。结果护理后研究组日常生活能力及康复情况评分均明显优于参照组,差异显著(P<0.05)。结论将优质护理干预应用于脊柱骨折合并脊髓损伤手术患者中,可有效提升其日常生活能力,促进康复,提升生存质量,值得临床推广。 展开更多
关键词 脊柱骨折 脊髓损伤 优质护理 应用价值
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外周血pNF-H、S100B水平与脊柱骨折伴脊髓损伤患者病情程度的相关性 认领
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作者 王晓林 曾凡伟 《新医学》 2020年第9期710-713,共4页
目的探讨外周血神经丝蛋白H磷酸化亚型(pNF-H)、S100B钙结合蛋白(S100B)水平与脊柱骨折伴脊髓损伤患者病情程度的相关性。方法选择238例脊柱骨折患者,根据其是否伴脊髓损伤分为脊髓损伤组71例与脊髓未损伤组167例,采用ELISA检测血清pNF-... 目的探讨外周血神经丝蛋白H磷酸化亚型(pNF-H)、S100B钙结合蛋白(S100B)水平与脊柱骨折伴脊髓损伤患者病情程度的相关性。方法选择238例脊柱骨折患者,根据其是否伴脊髓损伤分为脊髓损伤组71例与脊髓未损伤组167例,采用ELISA检测血清pNF-H、S100B水平,比较2组血清pNF-H、S100B水平,对比病情不同严重程度的脊柱骨折伴脊髓损伤患者血清pNF-H、S100B水平,绘制受试者工作特征(ROC)曲线分析血清pNF-H、S100B水平对脊柱骨折伴脊髓损伤的诊断价值。结果脊髓损伤组血清pNF-H、S100B水平高于脊髓未损伤组(P均<0.05)。脊髓完全损伤的脊柱骨折患者血清pNF-H、S100B水平高于脊髓不完全损伤的脊柱骨折患者(P均<0.05)。血清pNF-H、S100B水平联合检测对脊柱骨折伴脊髓损伤的ROC曲线下面积均高于单独检测(P均<0.05)。结论pNF-H、S100B水平在脊柱骨折伴脊髓损伤患者外周血中高表达,并与脊柱骨折伴脊髓损伤患者病情严重程度相关,检测血清pNF-H、S100B水平有助于脊柱骨折伴脊髓损伤早期诊断及病情严重程度评估。 展开更多
关键词 神经丝蛋白H磷酸化亚型 S100B钙结合蛋白 脊柱骨折 脊髓损伤 表达水平 病情严重程度 相关性
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Autar风险评估护理在脊柱骨折合并脊髓损伤手术患者中的应用 认领
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作者 胡桂芳 朱孝丽 《齐鲁护理杂志》 2020年第12期25-28,共4页
目的:探讨Autar风险评估护理在脊柱骨折合并脊髓损伤手术患者中的应用方法及效果。方法:将182例脊柱骨折合并脊髓损伤手术患者按入院顺序分为对照组和观察组各91例,对照组给予常规护理干预,观察组在此基础上实施Autar风险评估护理,比较... 目的:探讨Autar风险评估护理在脊柱骨折合并脊髓损伤手术患者中的应用方法及效果。方法:将182例脊柱骨折合并脊髓损伤手术患者按入院顺序分为对照组和观察组各91例,对照组给予常规护理干预,观察组在此基础上实施Autar风险评估护理,比较两组护理效果。结果:两组患者干预后血流平均速度、血流峰速度高于干预前(P<0.05),观察组干预后血流平均速度、血流峰速度高于对照组(P<0.05)。观察组干预后并发症发生率低于对照组(P<0.05),护理总满意率高于对照组(P<0.05)。结论:Autar风险评估护理可有效评估脊柱骨折合并脊髓损伤手术患者的术后深静脉血栓风险,促进患者术后血流速度和血流峰速度,降低术后并发症发生率,提高护理满意度。 展开更多
关键词 脊柱骨折 脊髓损伤 Autar风险评估护理 术后深静脉血栓 护理满意度
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Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries:a meta-analysis 认领
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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 《中国神经再生研究:英文版》 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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脊髓损伤增强α-肾上腺素受体的股动脉表达和反应性变化 认领
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作者 秦础强 朱翔 +3 位作者 曾展鹏 赵洪普 吕玉明 曾敬 《泰山医学院学报》 CAS 2020年第8期564-567,共4页
目的探究脊髓损伤增强α-肾上腺素受体的股动脉表达和反应性变化。方法本研究共使用48只大鼠,随机分为对照组(n=24)和脊髓损伤组(n=24)。在麻醉大鼠中,使用力校准体重下降装置在T10水平诱导持续性脊髓损伤。严重脊髓损伤后两周,测量股... 目的探究脊髓损伤增强α-肾上腺素受体的股动脉表达和反应性变化。方法本研究共使用48只大鼠,随机分为对照组(n=24)和脊髓损伤组(n=24)。在麻醉大鼠中,使用力校准体重下降装置在T10水平诱导持续性脊髓损伤。严重脊髓损伤后两周,测量股动脉血流,分析α-肾上腺素受体的血管舒缩功能和表达。利用蛋白质印迹分析α-肾上腺素受体蛋白表达量。通过组织形态学观察动脉组织情况。结果股动脉血流量在POD1几乎检测不到,在POD 7和14逐渐增加,然而,在脊髓损伤后14 d,股动脉血流量仍然显著降低。脊髓损伤大鼠股动脉血流明显减少。脊髓损伤大鼠股动脉段对α-肾上腺素能激动剂苯肾上腺素累积增加的收缩反应显著增强。大鼠股动脉血管匀浆内层α-肾上腺素能受体表达上调。Western blot实验结果表明髓损伤大鼠α-肾上腺素能受体蛋白水平明显上调;组织学测定结果表明,股动脉内侧层α-肾上腺素能受体表达增强,脊髓损伤大鼠股动脉HE染色显示相似的形态。结论肾上腺素受体在动脉平滑肌层的补偿表达增多的脊柱损伤水平下的延伸抗原,增强了对α-肾上腺素激动剂的响应性,并增强了自主异常发育的潜力。 展开更多
关键词 脊髓损伤 Α-肾上腺素受体 去肾上腺素
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全程优质护理干预对脊柱骨折合并脊髓损伤手术患者干预效果及生活质量的影响 认领 被引量:1
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作者 张晶 刘秀清 张超 《长春中医药大学学报》 2020年第3期580-583,共4页
目的探讨全程优质护理干预对脊柱骨折合并脊髓损伤手术患者干预效果及生活质量的影响。方法选取136例脊柱骨折合并脊髓损伤的手术治疗患者,根据随机抽签原则将受试者分为对照组和研究组,各68例。其中对照组接受传统的围术期护理,研究组... 目的探讨全程优质护理干预对脊柱骨折合并脊髓损伤手术患者干预效果及生活质量的影响。方法选取136例脊柱骨折合并脊髓损伤的手术治疗患者,根据随机抽签原则将受试者分为对照组和研究组,各68例。其中对照组接受传统的围术期护理,研究组在对照组的基础上接受全程优质护理干预,比较2组的干预效果及生活质量。结果干预后2组SAS与SDS评分均较干预前均明显降低,且研究组显著低于对照组(P<0.05);研究组术后VAS评分与住院时间显著少于对照组,康复情况及护理满意度评分显著高于对照组(P<0.05);研究组并发症发生率较对照组更低,2组比较差异性显著(P<0.05);干预后2组生活质量评分均明显提高,且研究组显著高于对照组(P<0.05)。结论全程优质护理干预有助于改善患者的负性情绪,减少术后并发症,促进患者术后康复,缩短住院时间,改善患者的生活质量,提高护理质量,在脊柱骨折合并脊髓损伤手术患者护理中具有较高的应用价值。 展开更多
关键词 全程优质护理干预 脊柱骨折 脊髓损伤 负性情绪 术后并发症 生活质量
脐血单核细胞移植治疗慢性完全性脊髓损伤Ⅱ期临床试验的安全性和疗效评估 认领
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作者 封亚平 Wise Young +8 位作者 朱辉 封雨 邓洵鼎 谢佳芯 张社敏 方芳 石静 陈永和 郑爽 《中华神经创伤外科电子杂志》 2020年第4期196-201,共6页
目的评估人类白细胞抗原(HLA≥4:6)配型的脐血单核细胞(UCBMC)移植治疗慢性完全性脊髓损伤(SCI)的安全性、可行性、有效性以及最佳细胞剂量和联合使用甲基强的松龙(MP)、碳酸锂对细胞移植的作用。方法选取联勤保障部队第九二〇医院神经... 目的评估人类白细胞抗原(HLA≥4:6)配型的脐血单核细胞(UCBMC)移植治疗慢性完全性脊髓损伤(SCI)的安全性、可行性、有效性以及最佳细胞剂量和联合使用甲基强的松龙(MP)、碳酸锂对细胞移植的作用。方法选取联勤保障部队第九二〇医院神经外科自2011年2月至2014年1月收治的20例SCI患者,按照随机数字表法分为5组(A、B、C、D、E组),每组4例受试者。在患者损伤上下缘脊神经背根入处的4个点(上下各2点)注射UCBMC,A、B、C组分别为每点各注射4、8和16μL(100000 UCBMC/μL,640万细胞)到SCI部位的上方和下方脊神经背根入处,D组为16μL细胞注射加30 mg/kg MP静脉注射,E组为16μL细胞注射加MP和口服碳酸锂(750 mg/d),一个疗程6周。受试者进行3~6个月的强化步行训练,以美国脊髓损伤协会(ASIA)为主要评分指标,脊髓损伤步行指数(WISCI)和脊髓独立量表(SCIM)为次要评分指标。结果20例受试者的SCI平面分别位于C3~T11,平均受伤7年。治疗前,16例(80%)患者行走<10 m,18例(90%)患者自理生活需要协助。治疗后41~87周,受试者ASIA运动评分无明显变化,而WISCI和SCIM评分明显提高。15例(75%)患者可在辅助下步行10 m,12例(60%)患者恢复膀胱和肠道控制,5例(25%)患者由完全性SCI变为不完全性SCI;所有患者无神经功能丢失。结论UCBMC移植和步行训练能提高慢性完全性SCI患者的WISCI和SCIM评分,但对运动评分没有改善,因此推测UCMBC移植能促进轴突的生长,从而激活中枢模式发生器,改善运动、排尿和排便等功能,而且联合使用MP和碳酸锂对细胞移植治疗无明显作用。 展开更多
关键词 脊髓损伤 脐血单核细胞 移植
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