应用胶原-壳聚糖桥接管引导大鼠坐骨神经再生

目的:观察胶原-壳聚糖桥接管促进大鼠坐骨神经损伤后再生与修复的作用。方法:用壳聚糖和胶原蛋白按1∶3的比例采用冷冻干燥法制成胶原-壳聚糖复合导管;将20只雄性Wistar大鼠随机分为2组,胶原-壳聚糖导管组和硅胶管组,切断坐骨神经,建立10mm的缺损动物模型;分别用胶原-壳聚糖导管和硅胶管进行桥接。于术后不同时间对2组动物进行大体观察,并于术后14周进行电生理、组织学及逆行示踪检测,比较2组大鼠坐骨神经的再生和功能恢复情况。结果:术后14周2组动物坐骨神经再生和功能恢复情况的各项检测指标显示,胶原-壳聚糖桥接组明显优于硅胶管桥接组。结论:胶原-壳聚糖导管可用来桥接损伤神经,在周围神经缺损修复方面具有良好的应用前景。     

静电纺丝聚乳酸聚乙醇酸共聚物-丝素-胶原神经导管修复大鼠周围神经缺损

背景：周围神经缺损修复是临床上一大难题,由于自体神经移植有一定的局限性,人工神经修复材料是一种很有前途的选择。 目的：探讨静电纺丝聚乳酸聚乙醇酸共聚物(PLGA)-丝素-胶原纳米神经导管修复大鼠坐骨神经缺损的可能性。 方法：雌性SD大鼠36只,制备约10 mm的坐骨神经缺损,分别采用倒转自体神经、静电纺丝PLGA-丝素-胶原神经导管、单纯PLGA神经导管桥接,术后12周进行大体观察、神经电生理测定、光镜观察、透射电镜观察和图像分析对比,了解神经再生的情况。 结果与结论：静电纺丝法制备成的纳米神经导管管壁疏松多孔,能够模拟细胞外基质的结构。静电纺丝PLGA-丝 素-胶原神经导管组在促进坐骨神经再生、提高再生神经髓鞘化、加速再生神经功能重建等方面均优于单纯PLGA导管组,比自体神经移植组略差。     

壳聚糖材料在神经导引管桥接周围神经缺损中的应用

应用壳聚糖材料制备神经导引管作为神经再生室桥接大鼠坐骨神经缺损,观察对神经再生的作用。手术造成90只Wistar大鼠右后肢坐骨神经长约15mm的缺损,A组以含有NGF的壳聚糖神经导引管桥接神经缺损,B组单纯采用壳聚糖导管,C组则不用导管,以左侧正常坐骨神经作为正常对照,分别于术后4、12、24周进行大体及显微解剖观察、组织学检查、电镜观察和神经电生理测定。结果表明,A、B组在促进神经再生,加快血管化进程,再生神经纤维排列规律化,提高再生神经髓鞘化,加速再生神经功能重建等方面均优于C组。壳聚糖是制备神经导引管的理想材料。壳聚糖神经导引管可以为大鼠坐骨神经再生提供良好的再生微环境。     

人工组织神经移植物辅加神经再生素修复大鼠周围神经缺损的实验研究

目的　用人工组织神经移植物辅加神经再生素 (NRF)桥接修复大鼠周围神经缺损。　方法　用壳聚糖套管和聚乙醇酸纤维制成人工组织神经移植物 ,辅加促神经生长的中药有效组分NRF ,桥接大鼠坐骨神经缺损10mm。术后作足迹试验 ;2 4周时对再生神经进行电生理学测试、形态学观察和计量学统计。　结果　术后 2 4周内 ,动物未见炎症及排斥反应。实验组的再生神经在足迹试验、电生理学、形态学及计量学上优于硅胶管桥接组。结论　人工组织神经移植物辅加NRF与周围神经组织具有良好的生物相容性 ;它对缺损的神经修复有较好的桥梁和促进作用     

大鼠坐骨神经缺损聚吡咯膜植入试验

了解大鼠神经组织对长期埋入其中的聚吡咯膜的生物学反应 ,同时观察聚吡咯涂层的硅胶管作为桥接物 ,修复周围神经缺损的可能性。在硅胶管内壁用电化学方法合成聚吡咯膜管涂层 ,并以桥接方法修复大鼠的坐骨神经缺损 10mm。术后 2 4周 ,对再生组织进行电生理学测试、组织形态学观察和计量学统计。在聚吡咯膜长期植入缺损神经期间 ,实验动物仅出现轻微炎症反应 ;聚吡咯膜管中可见到再生神经 ;聚吡咯膜管内再生的神经在电生理学、组织形态学及计量学方面的结果均略优于单纯的硅胶管桥接组。实验表明在体内周围神经组织对长期埋入的聚吡咯未产生不良反应。     

复合转化生长因子-β的组织工程化周围神经修复坐骨神经缺损

探讨了转化生长因子-β(Transforming growth factor-β,TGF-β)在周围神经缺损修复中的作用。将50 ng·ml-1 TGF-β加入体外培养的雪旺细胞(Sehwann cells,SC)中,MTT和流式细胞仪观测到TGF-β能够明显促进SC增殖;ELISA方法检测到TGF-β组上清神经生长因子(NGF)含量高于对照组(P<0．05);将牛去细胞基质(Bovine acellular matrix,BAM)、SC、血清和培养基按一定的比例混合,注入聚乳酸羟基乙酸共聚物(PLGA)神经导管去修复15 mm坐骨神经缺损。30只SD大鼠分为3组,实验组:PLGA导管 SC TGF-β;空白组PLGA导管 SC;和自体神经移植组。16周后通过电生理、透射电镜等检测方法显示各组坐骨神经均得到再生,修复效果实验组与自体神经移植组无显著性差异,均优于空白组。TGF-β一方面可以明显促进SC的增殖,另一方面可以增强SC分泌NGF的功能。因此周围神经修复过程中使用外源性的TGF-β对修复周围神经缺损有较好的疗效。     

移植壳聚糖导管修复大鼠坐骨神经缺损

目的:研究移植结合了碱性成纤维细胞生长因子(bFGF)的壳聚糖导管促进周围神经损伤再生的情况。方法:成年Wistar大鼠造成10mm坐骨神经缺损后,以壳聚糖导管(移植组,10只)作桥梁桥接神经两断端,以假手术组和单纯损伤组(造成10mm坐骨神经缺损后,不加以任何干预措施)各10只分别为阳性和阴性对照,术后通过肉眼观察和神经微丝(NF)、乙酰胆碱酯酶(AChE)免疫组织化学染色方法对损伤神经局部及远端靶肌肉运动终板的再生情况进行观察。结果:移植组大鼠术后3个月,新生的神经纤维已越过缺损部位并到达损伤远端。免疫组织化学染色显示:术后3个月,移植组大鼠坐骨神经缺损处再生组织内可观察到均匀、密集分布的NF免疫阳性纤维,且在腓肠肌终板区内可见AChE免疫阳性终末,至5个月时阳性染色明显增强。在术后3个月时可见新生的运动终板,但轮廓不规则、边界不清晰;而在5个月时,新生的运动终板的形态与密度均接近假手术组水平。结论:结合了bFGF的壳聚糖导管对缺损的坐骨神经修复具有良好的桥梁作用和促进神经生长及终板再生的作用。     

神经细胞外基质材料制备及修复周围神经缺损的实验研究

目的 :制备一种新型天然神经细胞外基质材料 ,通过动物实验研究 ,探讨其修复周围神经干节段性缺损的可行性。方法 :采用NaOH消蚀法 ,制备家兔坐骨神经细胞外基质材料 ,行扫描电镜观察及生物相容性实验 ,用于桥接修复家兔坐骨神经节段性缺损并以自体神经修复作为对照 ,术后通过肌电图检测、再生神经纤维组织学观察等方法 ,证实该支架可有效地引导和促进神经纤维再生。结果 :(1)经NaOH消蚀处理的坐骨神经组织 ,其细胞成分被完全消蚀掉 ,神经膜管保持原有的构筑特征 ;无明显排异反应并可降解吸收。 (2 )该材料和自体神经移植修复周围神经干节段性缺损在电生理和组织结构的恢复方面经统计学处理无显著性差异 (P >0 .0 5 )。结论 :此方法制备的细胞外基质材料可有效地桥接修复周围神经干节段性缺损 ,为其临床应用奠定实验基础。     

改性壳聚糖防粘连膜修复坐骨神经损伤

背景:研究表明壳聚糖与动物及人体具有较好的生物相容性、可降解性,可支持许旺细胞在壳聚糖膜上生长,而且能够明显抑制成纤维细胞生长。目的:观察改性壳聚糖防粘连膜对大鼠坐骨神经再生修复的影响。方法:切断60只SD大鼠双侧坐骨神经,缝合外膜,随机在一侧坐骨神经缝合处包裹改性壳聚糖防粘连膜,以另一侧为对照。术后20,30,40d进行电生理及组织学检测,观察改性壳聚糖防粘连膜对大鼠坐骨神经损伤修复的影响。结果与结论:早期改性壳聚糖防粘连膜治疗侧神经断端的炎性反应较对照侧明显,随着膜的自行降解,炎症反应逐渐减轻,神经缝合口纤维组织增生减少。与对照侧相比,大鼠坐骨神经损伤30d后,改性壳聚糖防粘连膜治疗侧神经传导速度恢复快,比目鱼肌记录到的神经-肌肉电潜伏期缩短(P0.05)。30d后各时点与对照侧比较,改性壳聚糖防粘连膜治疗侧坐骨神经再生轴索密度大于对照侧(P0.05)。说明改性壳聚糖防粘连膜虽早期会加重周围神经损伤的炎性反应,但随着膜的降解,炎症反应逐渐减轻,可减轻神经缝合口纤维组织增生,防止粘连,因而有利于神经传导速度恢复及轴索生长。     

脱细胞同种异体神经移植物修复大鼠坐骨神经缺损的实验研究

目的 观察脱细胞处理的同种异体神经移植物修复大鼠坐骨神经缺损的作用。方法 用组织工程学方法制备的大鼠同种异体神经移植物桥接大鼠坐骨神经缺损，并对再生神经进行电生理学功能测试，光镜、电镜观察移植物内的再生神经，并进行统计分析。结果 术后13周内，动物未见炎症及排斥反应。用脱细胞处理的同种异体神经移植物修复神经缺损，再生神经的传导功能、纤维数量、轴突直径、有髓纤维占有的面积与自体神经移植对照及计量学上统计分析均无显著性差异。结论 脱细胞处理的同种异体神经移植物具有良好的组织相容性，它对缺损的坐骨神经再生有促进作用。     

神经导管修复周围神经损伤的研究进展

随着神经修复技术特别是显微外科的发展，神经损伤修复的质量有了进一步的提高；利用神经导管桥接神经断端以实现修复周围神经损伤是目前的一个研究热点。本综述了神经导管修复周围神经损伤的发展历史，分析比较了非神经组织、非生物降解材料、可生物降解材料神经导管在神经损伤修复中的效果，讨论了导管的形态及导管内微环境对神经再生的影响。     

神经导管修复周围神经损伤的研究进展

对神经导管在周围神经损伤的修复和再生的应用及研究进展作一综述。主要包括两方面内容：神经导管材料设计及导管内微环境构建。     

Fabrication Techniques of Nerve Guidance Conduits for Nerve Regeneration

Neuronal loss and axonal degeneration after spinal cord injury or peripheral injury result in the loss of sensory and motor functions. Nerve regeneration is a complicated and medical challenge that requires suitable guides to bridge nerve injury gaps and restore nerve function. Due to the hostility of the microenvironment in the lesion, multiple conditions should be fulfilled to achieve improved functional recovery. Many nerve conduits have been fabricated using various natural and synthetic polymers. The design and material of the nerve guide conduits were carefully reviewed. A detailed review was conducted on the fabrication method of the nerve guide conduit for nerve regeneration. The typical fabrication methods used to fabricate nerve conduits are dip coating, solvent casting, micropatterning, electrospinning, and additive manufacturing. The advantages and disadvantages of the fabrication methods were reported, and research to overcome these limitations was reviewed. Extensive reviews have focused on the biological functions and in vivo performance of polymeric nerve conduits. In this paper, we emphasize the fabrication method of nerve conduits by polymers and their properties. By learning from the existing candidates, we can advance the strategies for designing novel polymeric systems with better properties for nerve regeneration.     

Peripheral Nerve Amyloidosis

Peripheral nerve amyloidosis is the cardinal feature of familial amyloid polyneuropathy (FAP) but can also be seen in primary light chain (AL) amyloidosis and dialysis (β₂-microglobulin) related amyloidosis. The generalized neuropathy seen in all forms of peripheral nerve amyloidosis is similar, characterized by a severe progressive mixed neuropathy with autonomic dysfunction. Pathologically, amyloid is found in the peripheral nervous system as amorphous, eosinophilic, extracellular deposits. FAP is most commonly associated with variant plasma transthyretin (TTR), although it has also been described in association with mutant apolipoprotein A-1 and gelsolin. There are now at least 36 point mutations in the TTR gene associated with FAP and these continue to be described. Recent studies on the possible role individual point mutations in the TTR gene may play in amyloidosis have helped give us an insight into the mechanisms behind peripheral nerve amyloidosis. This article reviews the clinical and pathological features of the peripheral nerve amyloidosis and discusses theories of amyloidogenesis based on studies of FAP.     

Heparin-Binding-Affinity-Based Delivery Systems Releasing Nerve Growth Factor Enhance Sciatic Nerve Regeneration

The controlled delivery of nerve growth factor (NGF) to the peripheral nervous system has been shown to enhance nerve regeneration following injury, although the effect of release rate has not been previously studied with an affinity-based delivery system (DS). The goal of this research was to determine if the binding site affinity of the DS affected nerve regeneration in vivo using nerve guidance conduits (NGCs) in a 13-mm rat sciatic nerve defect. These DSs consisted of bi-domain peptides that varied in heparin-binding affinity, heparin and NGF, which binds to heparin with moderate affinity. Eight experimental groups were evaluated consisting of NGF with DS, control groups excluding one or more components of the DS within silicone conduits and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry. These DSs with NGF resulted in a higher frequency of nerve regeneration compared to control groups and were similar to the nerve isograft group in measures of nerve fiber density and percent neural tissue, but not in total nerve fiber count. In addition, these DSs with NGF contained a significantly greater percentage of larger diameter nerve fibers, suggesting more mature regenerating nerve content. While there were no differences in nerve regeneration due to varying peptide affinity with these DSs, their use with NGF enhanced peripheral nerve regeneration through a NGC across a critical nerve gap.     

Gastrointestinal Autonomic Nerve Tumor

The article describes a case of gastrointestinal autonomic nerve tumor, which is histogenetically related to the gastrointestinal autonomic plexus (hence the name plexosarcoma). This rare and only recently recognized tumor of the gastrointestinal tract appears to have significant prognostic implications. This tumor cannot be diagnosed unequivocally by light microscopic and immunocytochemical examinations but shows characteristic electron microscopic features. The present case occurred as a gastric primary tumor and exhibited a light and electron microscopic picture similar to the one described in previous reports: areas of spindle-shaped and epithelioid cells, cytoplasmic processes with dense-core granules, and cytoplasmic intermediate filaments. Ultrastructural characteristics diagnostic of other gastrointestinal tumors, such as those originating from smooth muscle, Schwann cell, or endocrine cell types, were absent. Immunocytochemically, the tumor was diffusely positive for vimentin and neuron-specific enolase and focally positive for neurofilament triplet protein (NFTP) 160. Negative staining was observed for NFTP 200, S-100 protein, desmin, somatostatin, chromogranin, keratins (AE1/AE3), and glial fibrillary acidic protein. Although gastrointestinal autonomic nerve tumor has been reported to have a deceptively low-grade malignant appearance by light microscopy, it follows an aggressive clinical course. This tumor showed a much higher mitotic rate (one mitosis per high-power field) than the rates of tumors reported previously. Moreover, it occurred in a much younger patient (20 years of age) compared to previously reported cases (45 to 66 years of age), with the exception of one other case (16 years of age).