生物材料应用于脊髓损伤修复的研究进展

脊髓损伤是人类致残率最高的疾患之一。治疗脊髓损伤的趋势是联合应用多种技术和手段,创造出最适宜神经细胞再生恢复的环境,达到功能恢复的目的。生物材料在结构和功能上的优良性质使得它在脊髓损伤和修复中具有很好的应用前景。近年来兴起的组织工程学方法更为脊髓损伤的治疗带来新思路,即通过种子细胞—支架材料—神经营养因子复合物修复受损脊髓。本文回顾了近年来组织工程支架和细胞载体系统在脊髓损伤修复中的应用,展示了生物材料在组织工程和细胞分子治疗策略中的优越性。     

脊髓损伤药物治疗进展

脊髓损伤(Spinalcordinjury,SCI)是严重危害人类健康的疾病,其后果严重。根据其病理机制分为原发性损伤和继发性损伤两个阶段及脊髓横断伤、完全性脊髓损伤、不完全性脊髓损伤及脊髓震荡伤四型。SCI治疗的药物主要有:甲基强的松龙、神经节苷酯、细胞生长因子、抗氧化剂及钙通道拮抗剂等。治疗方法虽多,但其治疗效果并不十分理想。结合了SCI病理演变的特性,对目前药物治疗的研究进展进行概述并提出展望。     

转基因治疗根性撕脱以及脊髓损伤的研究进展（英文）

根性撕脱伤和脊髓损伤是临床上非常重要的疾病,临床治疗方法很多,但难以成功治愈根性撕脱和脊髓损伤引起的瘫痪或慢性疼痛.基因治疗有可能为有效地治疗根性撕脱伤和脊髓损伤,并减轻对病人、家庭、医疗机构和世界经济的影响.癌症的治疗中基因治疗已解决了临床许多挑战性的问题,靶点基因的脊髓损伤研究从实验室走向临床.本综述从臂丛神经撕脱伤和脊髓损伤相关的血脊髓屏障的解剖和病理表现,脊髓损伤和根性撕脱伤基因治疗的种类,以及治疗脊髓损伤活体动物应用到的基因转运载体的种类,重点阐述病毒和非病毒载体转基因治疗在脊髓的转运路径.靶向脊髓的基因治疗已有很长时间,但仍然有问题没有解决,尤其是如何有效地转导病毒载体入在体动物的神经元仍未清楚.在病毒载体的安全性和设计上的问题未解决之前,临床治疗尚需进一步研究.     

脊髓损伤病人围手术期的心理护理

脊髓损伤病人受伤后出现的否认、焦虑、抑郁、愤怒、迫切、自卑、依赖、自我调整、适应等不同的心理变化,直接影响疾病治疗的进程和效果。外科手术是治疗脊髓损伤最为有效的方法之一,对脊髓损伤患者进行围手术期(手术前、手术中、手术后)的心理干预和心理护理非常必要。本文对脊髓损伤患者围手术期的心理护理进行综述,表明实施有效的心理护理,可减轻患者焦虑、抑郁、恐惧等情绪,提高病人的生活自理能力与生活质量。     

间充质干细胞来源外泌体修复创伤性脊髓损伤

创伤性脊髓损伤能够引起严重的神经功能障碍,是一种严重影响生活质量的疾病,但是尚无有效的治疗方法.现有研究中发现间充质干细胞来源的外泌体具有和母细胞相似的生理作用,将外泌体应用于脊髓损伤的治疗中表现出令人满意的疗效,而且移植外泌体后尚未发现在移植干细胞中出现的致瘤等副作用,因此外泌体将会是脊髓损伤治疗中一个很有前景的策略.现将间充质干细胞来源外泌体在治疗创伤性脊髓损伤中的研究进展进行综述,分析目前存在的问题和未来的研究方向.     

《中国学术期刊文摘》综述文摘选登

脊柱脊髓损伤的修复与重建进展张宁(南京医科大学第一附属医院脊柱外科中心,南京210029)阐明脊柱脊髓损伤临床与基础的最新进展。通过广泛查阅文献,并结合自身的研究结果和临床经验,对近年来脊柱脊髓损伤的临床治疗和基础研究进行总结。上颈椎骨折脱位的治疗,以侧块螺钉和椎弓根钉为基础的枕颈融合和寰枢椎融合技术不仅固     

体育功能锻炼对截瘫患者康复影响及评价分析

目的:探讨体育功能锻炼对截瘫患者后期康复治疗的影响及康复评价.方法:76例在脊髓损伤后出现截瘫患者,进行体育功能锻炼的康复治疗,追踪记录,采用美国脊髓损伤学会(ASIA)脊髓损伤神经功能分类国际标准评价康复效果.结果:经统计,胸腰髓不完全损害者康复锻炼前后ASIA损伤评分运动、感觉评分均有显著意义(P<0.05).胸腰髓完全损伤者运动、感觉ASIA评分好转较明显(P<0.05).结论:体育功能锻炼能帮助截瘫患者后期恢复,显著改善和提高患者的综合功能.     

神经干细胞移植的研究近况

神经干细胞能够再生和自我更新,并可以分化为神经元、星形胶质细胞和少突胶质细胞,因而神经干细胞移植可用于神经变性、脊髓损伤和神经脱髓鞘等疾病的治疗.本文主要总结了神经干细胞移植在帕金森氏病、脱髓鞘症、脊髓损伤、阿耳茨海默氏病和脑中风治疗中的应用.     

湿性愈合理论在治疗脊髓损伤患者压疮中的应用

目的:观察湿性愈合理论在治疗脊髓损伤患者并发压疮中的效果.方法:选取我院康复医学科2016年10月~2017年3月收治的36例脊髓损伤并发压疮的患者,随机分为试验组和对照组,每组均为18例,试验组采用湿性愈合方法,对照组采用干性愈合方法,观察两组患者住院期间压疮愈合的情况.结果:36例脊髓损伤所致的压疮患者经过严密的观察和精心的护理,试验组患者住院期间压疮的疗效及压疮愈合的时间均比对照组好,两组比较,其差异有统计学意义(P0.05).结论:湿性愈合理论在脊髓损伤患者并发压疮中效果显著,有利于患者的早日康复.     

激素治疗急性脊髓损伤的研究进展

综述了激素治疗急性脊髓损伤方面的研究进展 ,内容涉及到其基础研究和临床应用。     

Preliminary animal studies on observation of injured spinal cord with intraoperative ultrasound backscatter microscopy

Many studies have shown that strategies of nerve regeneration and cell-based transplantation are valid based on animal models of spinal cord injury (SCI).To apply these strategies and bridge spinal cord defects,the identification and precise localization of lesions during spinal cord surgery is necessary.The aim of the present experiment was to evaluate the capabilities of ultrasound backscatter microscopy (UBM) in identifying morphologic changes after SCI.After laminectomy,high-resolution ultrasound images of the spinal cord were obtained in one normal and seven spinal cord-injured adult Wistar rats using a UBM system with a 55-MHz center frequency scanner.Comparison between histoanatomic and UBM images was also performed.The results showed that UBM can identify cysts after the experimental SCI is removed in adult rats.In addition,the glial scar formed in secondary injury showed obvious hyperechoic speckle in the UBM image and correlated with the histoanatomic image.UBM has obvious clinical value in nerve regeneration and cell-based transplantation strategies in injured spinal cords.     

Spinal cord decompression reduces rat neural cell apoptosis secondary to spinal cord injury

Objective: To determine whether spinal cord decompression plays a role in neural cell apoptosis after spinal cord injury. Study design: We used an animal model of compressive spinal cord injury with incomplete paraparesis to evaluate neural cell apoptosis after decompression. Apoptosis and cellular damage were assessed by staining with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) and immunostaining for caspase-3, Bcl-2 and Bax. Methods: Experiments were conducted in male Sprague-Dawley rats (n=78) weighing 300~400 g. The spinal cord was compressed posteriorly at T10 level using a custom-made screw for 6 h, 24 h or continuously, followed by decompression by removal of the screw. The rats were sacrificed on Day 1 or 3 or in Week 1 or 4 post-decompression. The spinal cord was removed en bloc and examined at lesion site, rostral site and caudal site (7.5 mm away from the lesion). Results: The numbers of TUNEL-positive cells were significantly lower at the site of decompression on Day 1, and also at the rostral and caudal sites between Day 3 and Week 4 post-decompression, compared with the persistently compressed group. The numbers of cells between Day 1 and Week 4 were immunoreactive to caspase-3 and B-cell lymphoma-2 (Bcl-2)-associated X-protein (Bax), but not to Bcl-2, correlated with those of TUNEL-positive cells. Conclusion: Our results suggest that decompression reduces neural cell apoptosis following spinal cord injury.     

Same impact momentum causes different degrees of spinal cord injury

The weight-drop impact is widely used in making animal model of spinal cord injury （SCI）. But there has not yet been an appropriate unit for the quantification of the impact. In this study, we compared the degrees of the spinal cord injury caused by weight-drop impact with the same momentum but different combinations of drop weight and drop height, in order to test whether ＂momentum＂ is capable of being the unit for the quantification of weight- drop impact. Thirty adult rats were randomly allocated to three groups and were injured with 5 g-10 cm （group A）, 10g-2.5 cm （group B） and 15 g-l.ll cm （group C） impacts with the same momentum to the spinal cord, respectively. Open-field locomotor function was evaluated using the Basso-Beattie-Bresnahan （BBB） locomotor rat- ing scale. The percentage of spared tissue area （STA） at the epicenter, and 500, 1000 and 1500 gm from the epicenter was calculated using serial sections stained by hematoxylin and eosin. As a result, the behavioral recovery （BBB scores） and the STA percentage were similar in group B and group C. However, the BBB score in group A was significantly lower than that in groups B and C at the same time point post injury. The STA percentage was signifi- cantly less and the lesion/cavity length was significantlygreater in group A than in groups B and C. These suggested that the 5 g-10 cm weight-drop impact, compared with the other two impacts with different weights and heights, caused a greater damage of the spinal cord when the momentum was the same. So, these impacts with the same momentum but different weights and drop heights cause different degrees of spinal cord injury. Momentum alone is inadequate to be the unit for the qualification of weight- drop impact and to be used to predict the extent of injury.     

New strategies for the repair of spinal cord injury

Spinal cord injury （SCI） leads to several neu- rologic damages to patients with sensory and motor func- tion loss. Although some inspiring results were reported in animal, even in non-human primate models, the clinical translation of these research achievements barely move forward for the SCI patients. This review mainly focused on the pathogenesis of the primary and secondary injury, the clinical therapies and the new technologies in spinal cord injury. Moreover, the key scientific issues on this field were discussed in the review. Finally, some suggestions were proposed for the scientific and clinical researches.     

大鼠脊髓楔型半切空洞模型的建立及评估

摘要: 目的建立一种新型大鼠脊髓半切模型,为临床脊髓空洞损伤研究提供适宜的动物模型。方法25 只SD 大鼠随机分为脊髓楔型块状半切组( A 组,n = 10) 、假手术组( B 组,n = 10) 和正常对照组( C 组,n = 5) 。术后采用 BBB 运动功能评分、斜板试验、HE 染色和核磁共振( MRI) 检测综合评价脊髓半切模型的稳定性。结果术后A 组 大鼠伤侧后肢BBB 运动功能评分及斜板维持最大角度值显著低于B 组和C 组( P ＜ 0. 05) ,而这些指标在B 组和C 组之间没有明显差异; 术后28 d HE 和MRI 检测显示脊髓损伤区( A 组) 灰质和白质发生明显的形态学改变。结论 通过该方法建立的脊髓半切模型稳定、可靠,适于脊髓空洞性损伤的研究。     

肽-DNA纳米颗粒用于HIF-1αΔODD转染脊髓损伤动物模型的研究

为了探讨肽-DNA纳米颗粒技术用于转染脊髓损伤动物模型的可能性,本研究在克隆得到氧浓度非敏感性的HIF-1α突变体基因(HIF-1αΔODD)并构建其真核重组表达载体(pEGFPC1-HIF-1αΔODD)的基础上,构建用于转染动物模型的肽-DNA纳米颗粒,将其转染脊髓损伤大鼠模型,用组织免疫荧光方法检测内/外源性HIF-1α在动物模型中的表达情况.结果显示,外源性HIF-1α在实验组脊髓组织中正确表达,说明构建的pEGFPC1-HIF-1αΔODD的肽-DNA纳米颗粒成功转染了稳定的脊髓损伤大鼠模型,肽-DNA纳米颗粒技术可作为中枢神经系统损伤动物模型的分子干预研究的一种新的选择.     

基因重组碱性成纤维细胞生长因子对大鼠脊髓损伤神经保护作用

目的 :探索碱性成纤维细胞生长因子 (bFGF)对大鼠脊髓损伤的神经保护作用 方法 :将吸入bFGF的胶原蛋白海绵或空白海绵贴敷于大鼠脊髓损伤处 ,术后 1、2、3周 ,对大鼠机能进行评分 ,并对大脑运动皮质进行电镜观察分析 结果 :术后 1、2、3周 ,bFGF组大鼠运动评分均明显优于对照组 (Ρ <0 .0 5) ,运动皮质电镜结果显示bFGF组线粒体、内质网轻度肿胀 ,神经毡结构正常 ,无明显胶质细胞增生 程度较对照组明显减轻 结论 :bFGF对大鼠脊髓受损神经纤维起源脑区—运动皮质的神经细胞具有明显的保护作用 ,进而使大鼠运动功能受损明显减轻     

泮托拉唑钠临床常用剂量对大鼠急性反流性食管炎动物模型的影响

目的观察泮托拉唑钠临床常用剂量治疗急性反流性食管炎的疗效。方法采用结扎幽门+贲门肌切开术制备大鼠急性反流性食管炎动物模型,观察泮托拉唑钠临床常用剂量对模型大鼠食管粘膜损伤指数的影响。结果泮托拉唑钠临床常用剂量能明显减轻大鼠急性反流性食管炎模型大鼠食管粘膜的损伤。结论泮托拉唑钠临床常用剂量对大鼠急性反流性食管炎模型大鼠具有一定的治疗作用。     

P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury

Pain after nerve damage is an expression of pathological operation of the nervous system, one hallmark of which is tactile allodynia-pain hypersensitivity evoked by innocuous stimuli. Effective therapy for this pain is lacking, and the underlying mechanisms are poorly understood. Here we report that pharmacological blockade of spinal P2X4 receptors (P2X4Rs), a subtype of ionotropic ATP receptor, reversed tactile allodynia caused by peripheral nerve injury without affecting acute pain behaviours in naive animals. After nerve injury, P2X4R expression increased strikingly in the ipsilateral spinal cord, and P2X4Rs were induced in hyperactive microglia but not in neurons or astrocytes. Intraspinal administration of P2X4R antisense oligodeoxynucleotide decreased the induction of P2X4Rs and suppressed tactile allodynia after nerve injury. Conversely, intraspinal administration of microglia in which P2X4Rs had been induced and stimulated, produced tactile allodynia in naive rats. Taken together, our results demonstrate that activation of P2X4Rs in hyperactive microglia is necessary for tactile allodynia after nerve injury and is sufficient to produce tactile allodynia in normal animals. Thus, blocking P2X4Rs in microglia might be a new therapeutic strategy for pain induced by nerve injury.