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Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy 被引量:16
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作者 Fei Yin Chunyang Meng +5 位作者 Rifeng Lu Lei Li Ying Zhang Hao Chen Yonggang Qin Li Guo 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第18期1665-1671,共7页
Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after trans- plantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are kno... Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after trans- plantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-as- sociated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Fur- thermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neuro- filament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mes- enchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury. 展开更多
关键词 nerve regeneration bone marrow mesenchymal stem cells spinal cord ischemia/reperfusioninjury axonal growth AUTOPHAGY repair NSFC grant neural regeneration
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髓鞘相关抑制因子及其受体在脊髓损伤修复中的研究进展
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作者 刘欣童 彭清华 +1 位作者 刘怀存 张卫光 《解剖学报》 CAS CSCD 2024年第3期371-377,共7页
脊髓损伤是一种严重的中枢神经系统创伤性疾病,常见于坠落伤、交通事故、重物砸伤等,可造成机体损伤平面以下的运动、感觉和自主神经功能障碍。髓鞘相关抑制因子(MAI)在损伤的脊髓微环境中具有促进生长锥塌陷、抑制轴突再生的作用,是造... 脊髓损伤是一种严重的中枢神经系统创伤性疾病,常见于坠落伤、交通事故、重物砸伤等,可造成机体损伤平面以下的运动、感觉和自主神经功能障碍。髓鞘相关抑制因子(MAI)在损伤的脊髓微环境中具有促进生长锥塌陷、抑制轴突再生的作用,是造成脊髓损伤难以修复的主要原因。髓鞘相关抑制因子类蛋白,如神经轴突生长抑制因子(Nogo)、少突胶质细胞髓鞘糖蛋白(OMgp)和髓鞘相关糖蛋白(MAG),及其受体蛋白如Nogo-A/Nogo-66受体1(NgR1)、配对免疫球蛋白样受体B(PirB)、鞘氨醇-1-磷酸受体(S1PR2),均是脊髓微环境中的重要调节因子,可通过影响神经元轴突生长的信号通路抑制脊髓损伤的修复过程。虽然目前脊髓损伤修复的机制还不清楚,但调节髓鞘相关抑制因子类蛋白及下游信号通路是脊髓损伤修复的重要治疗途径之一。我们通过本文对近年来MAI类蛋白及其受体在脊髓损伤修复中的作用进行综述,为脊髓损伤修复提供可探究的新靶点,并为脊髓损伤后的临床治疗提供更多思路。 展开更多
关键词 脊髓损伤 脊髓损伤修复 轴突损伤 髓鞘相关抑制因子
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End-to-end and end-to-side neurorrhaphy between thick donor nerves and thin recipient nerves:an axon regeneration study in a rat model 被引量:5
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作者 Tohru Tateshita Kazuki Ueda Akiyoshi Kajikawa 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第4期699-703,共5页
During nerve reconstruction,nerves of different thicknesses are often sutured together using end-to-side neurorrhaphy and end-to-end neurorrhaphy techniques.In this study,the effect of the type of neurorrhaphy on the ... During nerve reconstruction,nerves of different thicknesses are often sutured together using end-to-side neurorrhaphy and end-to-end neurorrhaphy techniques.In this study,the effect of the type of neurorrhaphy on the number and diameter of regenerated axon fibers was studied in a rat facial nerve repair model.An inflow-type end-to-side and end-to-end neurorrhaphy model with nerve stumps of different thicknesses(2:1 diameter ratio) was created in the facial nerve of 14 adult male Sprague-Dawley rats.After 6 and 12 weeks,nerve regeneration was evaluated in the rats using the following outcomes:total number of myelinated axons,average minor axis diameter of the myelinated axons in the central and peripheral sections,and axon regeneration rate.End-to-end neurorrhaphy resulted in a significantly greater number of regenerated myelinated axons and rate of regeneration after 6 weeks than end-to-side neurorrhaphy;however,no such differences were observed at 12 weeks.While the regenerated axons were thicker at 12 weeks than at 6 weeks,no significant differences in axon fiber thickness were detected between end-to-end and end-toside neurorrhaphy.Thus,end-to-end neurorrhaphy resulted in greater numbers of regenerated axons and increased axon regeneration rate during the early postoperative period.As rapid reinnervation is one of the most important factors influencing the restoration of target muscle function,we conclude that end-to-end neurorrhaphy is desirable when suturing thick nerves to thin nerves. 展开更多
关键词 epineural window transplantation nerve reconstruction SUTURING facial nerve repair axonal repair NEUROSURGERY peripheral nerve neural regeneration
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Delayed peripheral nerve repair: methods, including surgical ‘cross-bridging' to promote nerve regeneration 被引量:3
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作者 Tessa Gordon Placheta Eva Gregory H.Borschel 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第10期1540-1544,共5页
Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow ove... Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts(cross-bridges) into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to ‘protect' chronically denervated Schwa nn cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries. 展开更多
关键词 peripheral nerve injury nerve repair nerve regeneration Schwann cells electrical nerve stimulation axon regeneration
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Polyethylene glycol restores axonal conduction after corpus callosum transection 被引量:1
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作者 Ravinder Bamba D.Colton Riley +3 位作者 Richard B.Boyer Alonda C.Pollins R.Bruce Shack Wesley P.Thayer 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第5期757-760,共4页
Polyethylene glycol(PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In... Polyethylene glycol(PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays(MEA) were used to measure mean firing rate(MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups(P 〈 0.01, P 〈 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion. 展开更多
关键词 nerve regeneration polyethylene glycol nerve repair axonal fusion central nerve injury axonal conduction corpus callosum neural regeneration
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Human umbilical cord Wharton's jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration 被引量:8
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作者 Hong Chen Yan Zhang +1 位作者 Zhijun Yang Hongtian Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第10期890-899,共10页
Human umbilical mesenchymal stem cells from Wharton's jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted in... Human umbilical mesenchymal stem cells from Wharton's jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths. 展开更多
关键词 neural regeneration stem cells spinal cord injury Wharton's jelly human umbilical mesenchymalstem cells oligodendrocyte precursor-like cells axon myelin sheath nerve repair grants-supportedpaper NEUROREGENERATION
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Bridging the gap:axonal fusion drives rapid functional recovery of the nervous system
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作者 Jean-Sébastien Teoh Michelle Yu-Ying Wong +1 位作者 Tarika Vijayaraghavan Brent Neumann 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第4期591-594,共4页
Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently self-repair.This inherent deficiency necessitates the need for new treatme... Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently self-repair.This inherent deficiency necessitates the need for new treatment options aimed at restoring lost function to patients.Compared to humans,a number of species possess far greater regenerative capabilities,and can therefore provide important insights into how our own nervous systems can be repaired.In particular,several invertebrate species have been shown to rapidly initiate regeneration post-injury,allowing separated axon segments to re-join.This process,known as axonal fusion,represents a highly efficient repair mechanism as a regrowing axon needs to only bridge the site of damage and fuse with its separated counterpart in order to re-establish its original structure.Our recent findings in the nematode Caenorhabditis elegans have expanded the promise of axonal fusion by demonstrating that it can restore complete function to damaged neurons.Moreover,we revealed the importance of injury-induced changes in the composition of the axonal membrane for mediating axonal fusion,and discovered that the level of axonal fusion can be enhanced by promoting a neuron's intrinsic growth potential.A complete understanding of the molecular mechanisms controlling axonal fusion may permit similar approaches to be applied in a clinical setting. 展开更多
关键词 axonal fusion axon regeneration nervous system repair nerve injury PHOSPHATIDYLSERINE functional repair axonal transport Caenorhabditis elegans
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许旺细胞源性外泌体促进损伤周围神经的修复与再生 被引量:4
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作者 袁博 谢利德 付秀美 《中国组织工程研究》 CAS 北大核心 2023年第6期935-940,共6页
背景:周围神经损伤是临床上的常见创伤。目前短距离神经损伤可以进行端-端吻合,长距离神经损伤常需要移植物桥接。许旺细胞源性外泌体可以提高神经元存活率、改善再生微环境、促进轴突再生,在周围神经损伤与修复领域具有很好的应用前景... 背景:周围神经损伤是临床上的常见创伤。目前短距离神经损伤可以进行端-端吻合,长距离神经损伤常需要移植物桥接。许旺细胞源性外泌体可以提高神经元存活率、改善再生微环境、促进轴突再生,在周围神经损伤与修复领域具有很好的应用前景。目的:综述许旺细胞源性外泌体在周围神经损伤后再生修复中的研究进展。方法:检索PubMed数据库、万方数据库和中国知网(CNKI)2000-2022年的相关文章。中文检索词:“许旺细胞,雪旺细胞,施万细胞,外泌体,细胞外囊泡,周围神经,外周神经,坐骨神经”;英文检索词:“Schwann cell,exosomes,vesicles,peripheral nerve,sciatic nerve”,对初步检索的文献根据纳入、排除标准进行筛选,共纳入52篇文献进行深度分析。结果与结论:①许旺细胞的增殖和迁移对周围神经损伤后的再生修复发挥重要作用,有多种信号通路介入受损周围神经的再生修复;②外泌体可以通过转移生物活性物质介导细胞间通讯以维持正常的生理过程,在周围神经损伤的修复治疗方面具有很大的潜力;③许旺细胞源性外泌体可以通过参与轴突再生和生长调节,发挥促进损伤神经再生修复的作用,为周围神经损伤的临床治疗提供理论依据。 展开更多
关键词 外泌体 许旺细胞 周围神经 轴突再生 损伤与修复 基因工程 组织工程 信号通路
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Use of nerve conduits for peripheral nerve injury repair:A Web of Science-based literature analysis
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作者 Jinniang Nan Xuguang Hu +2 位作者 Hongxiu Li Xiaonong Zhang Renjing Piao 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第35期2826-2833,共8页
OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair... OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA: Inclusion criteria: peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. RESULTS: A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurge and Joumal of Biomedical Materials Research PartA. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION: Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus. 展开更多
关键词 nerve conduit biomaterial axon neurotrophic factor stem cell extracellular matrix peripheralnerve injury peripheral nerve repair degradation BIOCOMPATIBILITY neural regeneration
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导电水凝胶治疗脊髓完全横断大鼠的安全性评估
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作者 蒋昇源 邓博文 +7 位作者 刘港 范筱 白惠中 陶经纬 赵毅 任敬佩 徐林 穆晓红 《中国组织工程研究》 CAS 北大核心 2023年第21期3314-3319,共6页
背景:水凝胶作为生物支架已被广泛应用于脊髓损伤的基础研究,基于脊髓组织的电信号传导特性,导电水凝胶已有初步探索及应用,但疗效及机制尚不明确。目的:初步探索导电水凝胶促进脊髓损伤后轴突再生的潜在机制,评估导电水凝胶作为生物支... 背景:水凝胶作为生物支架已被广泛应用于脊髓损伤的基础研究,基于脊髓组织的电信号传导特性,导电水凝胶已有初步探索及应用,但疗效及机制尚不明确。目的:初步探索导电水凝胶促进脊髓损伤后轴突再生的潜在机制,评估导电水凝胶作为生物支架修复脊髓损伤的安全性与可行性。方法:在甲基丙烯酰化明胶水凝胶的基础上添加导电颗粒聚吡咯,制备导电水凝胶。将36只成年雌性SD大鼠随机分为假手术组、模型组和导电水凝胶组,每组12只。假手术组仅行椎板切除,模型组和导电水凝胶组建立T_(9)脊髓完全横断模型,缺损间隙2 mm,导电水凝胶组造模后立即予以导电水凝胶填塞缺损间隙。术后1,3,7,14,28 d进行大鼠BBB评分;术后28 d,进行血清炎性指标、肝脾肾及脊髓组织形态、微血管再生及轴突再生检测。结果与结论:①术后28 d,导电水凝胶组BBB评分优于模型组(P<0.05);②导电水凝胶组C-反应蛋白水平低于模型组(P<0.05),两组血沉比较差异无显著性意义(P>0.05);③苏木精-伊红染色显示,3组大鼠的肝、脾、肾等实质性器官无炎性细胞浸润;模型组断端处炎性细胞浸润明显,细胞排列紊乱,周围组织溶解;导电水凝胶组炎性细胞较少,细胞排列相对规整;Masson染色显示,模型组断端有大量胶原纤维长入,导电水凝胶组导电水凝胶周围仅被少量胶原纤维包裹;④免疫荧光染色显示,模型组脊髓缺损处血管内皮细胞较少,无成熟神经元细胞存在,导电水凝胶组血管内皮细胞明显多于模型组,有成形的血管轮廓,神经元数量较模型组多,但相较于假手术组细胞核固缩;⑤Western blot检测显示,导电水凝胶组血管内皮生长因子、神经丝蛋白200的蛋白表达量高于模型组(P<0.05);⑥导电水凝胶作为生物支架修复脊髓损伤安全有效,其促进轴突再生的机制可能与促微血管再生、改善微循环有关。 展开更多
关键词 脊髓损伤 水凝胶 导电水凝胶 血管新生 轴突再生 神经修复
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基于RhoA/ROCK通路探讨电针心包经穴对急性脑缺血大鼠神经轴突生长抑制因子的影响
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作者 唐雅妮 肖豆 +5 位作者 马文娟 谢峥嵘 潘江 娄必丹 章薇 陈成 《中国中医药信息杂志》 CAS CSCD 2023年第9期122-128,共7页
目的基于RhoA/ROCK通路观察电针心包经穴对脑缺血大鼠的调控作用,探讨其对急性脑缺血后神经修复的作用机制。方法将90只SD大鼠随机分为空白组、假手术组、模型组、心包经组、肺经组,除空白组和假手术组外,采用颈外动脉插入线栓法建立大... 目的基于RhoA/ROCK通路观察电针心包经穴对脑缺血大鼠的调控作用,探讨其对急性脑缺血后神经修复的作用机制。方法将90只SD大鼠随机分为空白组、假手术组、模型组、心包经组、肺经组,除空白组和假手术组外,采用颈外动脉插入线栓法建立大脑中动脉栓塞(MCAO)模型,造模成功后次日,心包经组、肺经组予电针治疗,分别于电针7、14、21 d后取材。HE染色观察梗死区脑组织病理变化,ELISA检测血清Ras同源基因家族成员A(RhoA)、Rho相关卷曲螺旋形成蛋白激酶(ROCK)Ⅱ含量,免疫组化检测梗死区脑组织RhoA、ROCKⅡ表达,RT-qPCR和Western blot检测梗死区脑组织RhoA、ROCKⅡmRNA和蛋白表达。结果与空白组、假手术组同一时点比较,模型组大鼠梗死区脑组织神经细胞数量减少,细胞核固缩,各时点血清RhoA、ROCKⅡ含量及梗死区脑组织RhoA、ROCKⅡmRNA和蛋白表达均明显升高(P<0.01);与模型组同一时点比较,心包经组大鼠梗死区脑组织神经细胞数量增加,形态结构改善,除7 d血清ROCKⅡ含量外,各时点血清RhoA、ROCKⅡ含量及梗死区脑组织RhoA、ROCKⅡmRNA和蛋白表达均明显降低(P<0.01,P<0.05),且心包经组作用优于肺经组(P<0.01,P<0.05)。结论电针心包经穴可下调急性脑缺血大鼠神经轴突生长抑制因子表达,其机制可能与抑制RhoA/ROCK通路相关。 展开更多
关键词 电针 心包经穴 急性脑缺血 神经轴突生长抑制因子 神经修复
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微管相关蛋白-1B在弥漫性轴索损伤中的表达变化与意义 被引量:2
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作者 张鹏 赵敏珠 +4 位作者 朱士胜 刘梦 高军 李红卫 李剑波 《重庆医科大学学报》 CAS CSCD 北大核心 2016年第1期34-37,共4页
目的 :观察微管相关蛋白-1B(microtubule-associate protein 1B,MAP1B)在SD大鼠弥漫性轴索损伤(diffuse axonal injury,DAI)后脑组织中表达的变化,探索其表达变化的意义。方法 :采用改良的Marmarou法建立SD大鼠DAI模型,分为空白对照组(1... 目的 :观察微管相关蛋白-1B(microtubule-associate protein 1B,MAP1B)在SD大鼠弥漫性轴索损伤(diffuse axonal injury,DAI)后脑组织中表达的变化,探索其表达变化的意义。方法 :采用改良的Marmarou法建立SD大鼠DAI模型,分为空白对照组(10只,不予任何处理),假打击组(10只,给予致伤组相同的打击前准备,但不予以打击),致伤6 h组(10只),致伤1 d组(10只)和致伤3 d组(10只),分别于打击6 h、1 d、3 d后,处死动物,提取脑组织,结合Western blot和免疫组化方法,观察SD大鼠脑组织中MAP1B表达的变化。结果:Western blot结果显示致伤6 h组(0.50±0.07)、致伤1 d组(0.56±0.07)和致伤3 d组(0.50±0.06)中MAP1B表达水平较空白对照组(0.30±0.06;P=0.001,P=0.000,P=0.001)、假打击组(0.30±0.04;P=0.001,P=0.000,P=0.001)明显升高。免疫组化结果显示致伤6 h组(4.70±0.79)、致伤1 d组(4.78±0.86)和致伤3 d组(4.70±0.89)中MAP1B表达水平较空白对照组(4.06±1.15;P=0.023,P=0.007,P=0.023)、假打击组(3.90±1.46;P=0.002,P=0.000,P=0.002)明显升高。结论:SD大鼠DAI后脑组织中MAP1B表达水平上调,提示其参与了DAI后轴索损伤的病理改变过程,并可能在稳定、修复及再生受损轴索的机制中起着重要作用。 展开更多
关键词 弥漫性轴索损伤 微管相关蛋白-1B 轴索修复 SD大鼠
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MBP68-86与MBP87-99诱导实验性自身免疫性脑脊髓炎大鼠的轴突损伤修复及其机制研究 被引量:1
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作者 赵晖 王义周 +4 位作者 寇爽 李明 齐放 张秋霞 王蕾 《首都医科大学学报》 CAS 2012年第3期285-290,共6页
目的观察髓鞘碱性蛋白(myelin basic protein,MBP)68-86及MBP87-99诱导实验性自身免疫性脑脊髓炎(experimentalautoimmune encephalomyelitis,EAE)大鼠模型中淀粉样前体蛋白(amyloid precursor protein,APP)及生长相关蛋白(growth-assoc... 目的观察髓鞘碱性蛋白(myelin basic protein,MBP)68-86及MBP87-99诱导实验性自身免疫性脑脊髓炎(experimentalautoimmune encephalomyelitis,EAE)大鼠模型中淀粉样前体蛋白(amyloid precursor protein,APP)及生长相关蛋白(growth-associatedprotein,GAP)-43mRNA表达及其环磷酸腺苷(cyclic adenosine monophosphate,cAMP)-蛋白激酶(protein kinase,PKA)的变化,探讨EAE大鼠发病过程中轴突损伤修复及其可能的分子机制。方法应用不同肽段的MBP68-86或MBP87-99与不完全福氏佐剂及结核杆菌混合制成抗原,皮下注射于大鼠双后足垫,建立大鼠EAE模型。观察其神经功能评分、脑组织病理变化,酶联免疫测定大鼠脑组织cAMP含量,实时荧光定量RT-PCR法测定大鼠脑组织APP、GAP-43及PKA mRNA表达。结果与MBP87-99组大鼠比较,MBP68-86所致EAE病情进展快,神经功能评分较高,炎细胞浸润重并形成袖套状改变。中剂量MBP68-86免疫大鼠第14天,脑组织GAP-43 mRNA表达较正常组明显降低(P<0.05);第28天,APP mRNA表达明显升高(P<0.05)。MBP87-99免疫大鼠第28天,APP mRNA表达较正常组和小剂量MBP68-86明显上升(P<0.05);GAP-43 mRNA表达较大、小剂量MBP68-86明显升高(P<0.05)。大、小剂量MBP68-86与MBP87-99免疫大鼠第28天,脑组织cAMP水平均较正常组明显增高(P<0.01或P<0.05),中剂量MBP68-86与MBP87-99组大鼠脑组织PKA mRNA表达明显升高(P<0.01)。结论 MBP68-86或MBP87-99均可诱导Lewis大鼠产生EAE。可引起脑组织的炎性细胞浸润、脱髓鞘及轴突损伤等,且损伤有一定的自我修复功能,其机制可能与调节cAMP-PKA信号途径有关。综合分析研究结果发现,MBP68-86中剂量(每只50μg)可作为探索EAE发病特点及药物观察的实验模型。 展开更多
关键词 实验性自身免疫性脑脊髓炎 髓鞘碱性蛋白 轴突损伤修复及其机制
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依达拉奉联合鼠神经生长因子对颅脑外伤患者神经功能损伤修复的效果 被引量:9
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作者 陈萍 路楷 《西北药学杂志》 CAS 2021年第1期117-121,共5页
目的分析依达拉奉联合鼠神经生长因子(mNGF)对颅脑外伤患者神经功能损伤修复的效果及对血中神经元特异性烯醇化酶(NSE)和轴索过度生长抑制因子-A(Nogo-A)表达水平的影响。方法将收治的105例颅脑外伤患者分为观察组和对照组;对照组采用... 目的分析依达拉奉联合鼠神经生长因子(mNGF)对颅脑外伤患者神经功能损伤修复的效果及对血中神经元特异性烯醇化酶(NSE)和轴索过度生长抑制因子-A(Nogo-A)表达水平的影响。方法将收治的105例颅脑外伤患者分为观察组和对照组;对照组采用依达拉奉治疗,观察组采用依达拉奉联合mNGF治疗;治疗前后采用美国国立卫生研究院卒中量表(NIHSS)评分及格拉斯哥昏迷指数(GCS)评分对患者神经功能及颅脑损伤严重程度进行调查,并检测患者血中神经功能、神经损伤指标、神经递质、炎症因子和应激激素水平;治疗前后检测患者血中NSE和Nogo-A表达水平。结果治疗后,观察组患者NIHSS评分显著低于对照组(P<0.05),GCS评分显著高于对照组(P<0.05);治疗后观察组脑源性神经营养因子(BDNF)水平高于对照组,髓鞘碱性蛋白(MBP)和缺血修饰白蛋白(IMA)水平低于对照组(P<0.05);治疗后观察组血中血管黏附蛋白-1(VAP-1)、强啡肽(Dny-A)、神经肽Y(NPY)、C反应蛋白(CRP)、核因子κB(NF-κB)、白细胞介素-1β(IL-1β)、皮质醇(Cor)、血管紧张素Ⅱ(AngⅡ)、去甲肾上腺素(NE)、促肾上腺皮质激素释放激素(CRH)水平、血中NSE及Nogo-A水平明显低于对照组(P<0.05)。结论依达拉奉联合mNGF治疗颅脑外伤患者可有效改善患者神经功能,加速损伤修复,并有效降低患者血中NSE和Nogo-A表达水平。 展开更多
关键词 依达拉奉 鼠神经生长因子 颅脑外伤 神经功能损伤修复 神经元特异性烯醇化酶 轴索过度生长抑制因子-A
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癌钙蛋白在视神经损伤修复中的作用及研究进展
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作者 赵亮 许家军 《国际眼科杂志》 CAS 2011年第10期1737-1739,共3页
作为一种特殊的钙调蛋白,癌钙蛋白(oncomodulin,OncoM,OCM)一直被认为只在肿瘤的发生、生长中起调节作用。然而近年来研究发现,OCM对视神经损伤具有修复功能,为神经损伤的治疗提供了更为广阔的视野。本文就目前OCM在视神经损伤修复中的... 作为一种特殊的钙调蛋白,癌钙蛋白(oncomodulin,OncoM,OCM)一直被认为只在肿瘤的发生、生长中起调节作用。然而近年来研究发现,OCM对视神经损伤具有修复功能,为神经损伤的治疗提供了更为广阔的视野。本文就目前OCM在视神经损伤修复中的作用及研究进展作一综述。 展开更多
关键词 癌钙蛋白 视神经损伤修复 轴突再生
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小鼠皮层神经元机械损伤后miR-124的动态变化及意义 被引量:10
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作者 苏鑫洪 叶玉勤 +1 位作者 杨永祥 贺晓生 《中华神经外科疾病研究杂志》 CAS 2017年第3期229-233,共5页
目的观察体外培养小鼠皮层神经元机械损伤后微小核糖核酸-124(miR-124)的表达变化,初步探讨miR-124对小鼠创伤性脑损伤后神经轴突再生与修复可能的影响。方法孕15~18 d C57BL/6种孕鼠胚胎脑皮质层神经元体外培养7 d,以10μL移液器塑料... 目的观察体外培养小鼠皮层神经元机械损伤后微小核糖核酸-124(miR-124)的表达变化,初步探讨miR-124对小鼠创伤性脑损伤后神经轴突再生与修复可能的影响。方法孕15~18 d C57BL/6种孕鼠胚胎脑皮质层神经元体外培养7 d,以10μL移液器塑料滴头在培养皿内划割,造成机械性损伤,伤后不同时间点(1 h,6 h,12 h,24 h,72 h,144 h)分别采用实时定量聚合酶链法(RTPCR)检测miR-124和蛋白质印记法(Western Blot)检测神经纤毛蛋白(Nrp-1)、微管相关蛋白(Tau)、生长相关蛋白43(Gap-43)的表达水平。然后用miR-124模拟物和抑制剂分别对体外培养的皮层神经元进行干预,观察miR-124表达量的改变对实验的影响。结果神经元机械损伤后miR-124和Nrp-1、Tau、Gap-43的表达均显著升高(P<0.05),且存在一定的正相关性。用miR-124模拟物和抑制剂分别显著升高和降低miR-124的表达后,Nrp-1、Tau、Gap-43表达显著下降,其中抑制剂组下降较模拟物组明显(P<0.05)。结论创伤区miR-124的适度高表达可能与轴突再生有密切联系,这为本课题组今后尝试梯度调控miR-124以调节神经轴突再生与修复提供了实验依据。 展开更多
关键词 机械损伤 微小核糖核酸-124 轴突再生修复
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Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries 被引量:4
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作者 George D.Bittner Dale R.Sengelaub Cameron L.Ghergherehchi 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第1期53-57,共5页
Current Neuroscience dogma holds that transections or ablations of a segment of peripheral nerves produce: (1) Immediate loss of axonal continuity, sensory signaling, and motor control; (2) Wallerian rapid (1-3 ... Current Neuroscience dogma holds that transections or ablations of a segment of peripheral nerves produce: (1) Immediate loss of axonal continuity, sensory signaling, and motor control; (2) Wallerian rapid (1-3 days) degeneration of severed distal axons, muscle atrophy, and poor behavioral recovery after many months (if ever, after ablations) by slowly-regenerating (1 mm/d), proximal-stump outgrowths that must specifically reinnervate denervated targets; (3) Poor acceptance of microsutured nerve allografts, even if tissue-matched and immune-suppressed. Repair of transections/ablations by neurorrhaphy and well-specified-sequences of PEG-fusion solutions (one containing polyethylene glycol, PEG) successfully address these problems. However, conundrums and confusions regarding unorthodox and dramatic results of PEG-fusion repair in animal model systems often lead to misunderstandings. For example, (1) Axonal continuity and signaling is re-established within minutes by non-specifically PEG-fusing (connecting) severed motor and sensory axons across each lesion site, but remarkable behavioral recovery to near-unoperated levels takes several weeks; (2) Many distal stumps of inappropriately-reconnected, PEG-fused axons do not ever (Wallerian) degenerate and continuously innervate muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (3) Host rats do not reject PEG-fused donor nerve allografts in a non-immuno-privileged environment with no tissue matching or immunosuppression; (4) PEG fuses apposed open axonal ends or seals each shut (thereby preventing PEG-fusion), depending on the experimental protocol; (5) PEG-fusion protocols produce similar results in animal model systems and early human case studies. Hence, iconoclastic PEG-fusion data appropriately understood might provoke a re-thinking of some Neuroscience dogma and a paradigm shift in clinical treatment of peripheral nerve injuries. 展开更多
关键词 axonal repair AXOTOMY Wallerian degeneration polyethylene glycol ALLOGRAFT AUTOGRAFT nerve regeneration
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Biological conduit small gap sleeve bridging method for peripheral nerve injury: regeneration law of nerve fibers in the conduit 被引量:8
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作者 Pei-xun Zhang Li-ya A +5 位作者 Yu-hui Kou Xiao-feng Yin Feng Xue Na Han Tian-bing Wang Bao-guo Jiang 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第1期71-78,共8页
The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair periph- eral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium su... The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair periph- eral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good his- tocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration (2-8 weeks), the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objec- tive and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury. 展开更多
关键词 nerve regeneration peripheral nerve small gap axonS Schwann cells repair injury biological conduit NSFC grants neural regeneration
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左乙拉西坦对难治性癫痫幼鼠海马组织中Slit2、srGAP2和GAP-43动态表达的影响 被引量:1
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作者 王影 张洋 +3 位作者 刘洁微 赵塔娜 邹艳红 聂磊 《黑龙江医药科学》 2021年第1期7-10,14,共5页
目的:探讨左乙垃西坦对难治性癫痫幼鼠海马组织中神经轴突导向因子2(Axon guidance factor 2,Slit2)、再生修复关键分子2(Key molecules for regeneration and repair 2,srGAP2)、生长相关蛋白43(Growth associated protein43,GAP-43)... 目的:探讨左乙垃西坦对难治性癫痫幼鼠海马组织中神经轴突导向因子2(Axon guidance factor 2,Slit2)、再生修复关键分子2(Key molecules for regeneration and repair 2,srGAP2)、生长相关蛋白43(Growth associated protein43,GAP-43)动态表达的影响。方法:选择我院动物医学中心培养的192只清洁级Wistar大鼠作为研究对象,将其称重编号之后,随机分为空白对照组、模型组(IE组)、治疗组(LEV治疗组)及LEV对照组,各48只。其中癫痫大鼠采用氯化锂-匹罗卡品(Licl-pilo)点燃造模。比较LEV治疗组与LEV对照组临床疗效、LEV治疗组与LEV对照组免疫指标水平、各组大鼠海马组织Slit2阳性细胞数、各组大鼠海马组织srGAP2蛋白相对表达量、各组大鼠海马组织GAP-43免疫组化染色强度。结果:(1)LEV治疗组总有效率为89.58%,显著高于对照组72.92%(P<0.05);(2)两组大鼠治疗后免疫指标(IgA、IgG及IgM)水平较治疗前均显著升高,且LEV治疗组上述指标水平也均分别显著高于LEV对照组治疗后(P均<0.05);(3)LEV对照组与对照组各个时间点的Slit2阳性细胞数差异均无统计学意义(P均>0.05),但IE组及LEV治疗组各个时间点的Slit2阳性细胞数均分别显著低于对照组(P均<0.05),LEV治疗组各个时间点的Slit2阳性细胞数均分别显著高于IE组(P均<0.05);(4)LEV对照组与对照组各个时间点的srGAP2蛋白相对表达量差异均无统计学意义(P均>0.05),但IE组及LEV治疗组各个时间点的srGAP2蛋白相对表达量均分别显著低于对照组(P均<0.05),LEV治疗组各个时间点的srGAP2蛋白相对表达量均分别显著高于IE组(P均<0.05);(5)LEV对照组与对照组各个时间点的GAP-43免疫组化染色强度差异均无统计学意义(P均>0.05),但IE组及LEV治疗组各个时间点的GAP-43免疫组化染色强度均分别显著低于对照组(P均<0.05),LEV治疗组各个时间点的GAP-43免疫组化染色强度均分别显著高于IE组(P均<0.05)。结论:LEV对难治性癫痫幼鼠疗效较为理想,可能是通过调节鼠马组织中Slit2、srGAP2和GAP-43动态表达水平而发挥效果。 展开更多
关键词 左乙拉西坦 难治性癫痫 海马组织 神经轴突导向因子2 再生修复关键分子2 生长相关蛋白43
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神经轴突损伤后再生修复的治疗展望
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作者 徐祥龙 张睿 赵承斌 《中国医药导报》 CAS 2013年第3期43-44,共2页
脊髓损伤的病因有脊髓休克、脊髓挫裂伤、脊髓受压。损伤的治疗主要是手术解除脊髓的压迫,利用内固定恢复脊柱的序列和稳定性,维持椎体的正常形态和椎间隙的高度。而手术对于神经细胞的损伤没有治疗作用。目前细胞移植是治疗脊髓神经损... 脊髓损伤的病因有脊髓休克、脊髓挫裂伤、脊髓受压。损伤的治疗主要是手术解除脊髓的压迫,利用内固定恢复脊柱的序列和稳定性,维持椎体的正常形态和椎间隙的高度。而手术对于神经细胞的损伤没有治疗作用。目前细胞移植是治疗脊髓神经损伤的重要手段,移植的细胞可以分化为神经元和神经胶质细胞,并分泌大量的神经生长因子,促进损伤后神经轴突的再生,对脊髓损伤和外周神经损伤治疗的研究有极大的推动作用。 展开更多
关键词 脊髓损伤 神经细胞修复 干细胞移植 轴突再生
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