Bridging the injured spinal cord with neural stem cells

Spinal cord injury （SCI） damages not only the gray matter neurons, but also the white matter axonal tracts that carry signals to and from the brain, re- suiting in permanent loss of function below injury. Neural stem cells （NSCs） have high therapeutic potential for reconstruction of the injured spinal cord since they can potentially fnrm neuronal relays to bridge functional con-nectivity between separated spinal cord segments. This requires host axonal regeneration into and connectivity with donor neurons, and axonal growth and connectivity of donor neurons to host central nervous system （CNS） circuitry. In this mini-review, we will discuss key studies that explore novel neuronal relay formation by grafting NSCs in models of SCI, with emphasis on long-distance axonal growth and connectivity of NSCs grafted into in-jured spinal cord.

Transplanting neural progenitors to build a neuronal relay across the injured spinal cord

Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,

Application and implications of polyethylene glycol-fusion as a novel technology to repair injured spinal cords

Conventional vs. polyethylene glycol （PEG）-fusion tech- nologies to repair severed spinal axons： Most spinal cord injuries （SCIs） involve cutor crush-severance of spinal tract axons in the central nervous system （CNS）. Clinical out- comes after CNS axonal severance is very poor because proximal segments of CNS axons lack a suitable environment for outgrowth （Kakulas, 1999; Fitch and Silver, 2008; Rowland et al., 2008; Kwon et al., 2010） and therefore do not naturally regenerate （Ramon y Caial, 1928）. Current strategies to try to increase behavioral recovery after SCI are focused on en- hancing the environment for axonal outgrowth.

Bridging large gaps in the injured spinal cord: mechanical and biochemical tissue adaptation

Incidence and consequences of spinal cord injuries： World- wide, every year 250,000-500,000 people suffer from spinal cord injury （SCI; www.who.int, 2013）. Traumatic lesions of the spinal cord lead to primary and secondary injury mechanisms, which result in axon damage, loss of signal conduction, demyelination of axons and long-lasting deficits in motor and sensory func- tion. The extent of the damage and the subsequent functional loss depend on the spinal level and the severity of the primary injury. Furthermore, pathophysiological and pathomorpholog- ical responses in acute and chronic SCI share similar but also different requirements for treatment.

Electrical stimulation of cortical neurons promotes oligodendrocyte development and remyelination in the injured spinal cord

Background and early studies： Endogenous tri-potential neural stem cells （NSCs） exist in the adult mammalian central nervous system （CNS）. In the spinal cord, NSCs distribute throughout the entire cord, but exist predominately in white matter tracts. The phenotypic fate of these cells in white matter is glial, largely oligodendrocyte, but not neuronal.

Repairing the injured spinal cord: sprouting versus regeneration. Is this a realistic match?

The article by Meves and Zheng （2014） is addressing a continu- ous shift in the field of spinal cord injury （SCI） research that has occurred over the last century. Before that, the spinal cord was viewed as ＂hard wired＂ and treatment considerations were based on observations that axons in the periphery were able to regenerate, but those in the central nervous system （CNS） were not （David and Aguayo, 1981）.

Effect of the implant composite of poly lactide-co-glycolide and bone mesenchymal stem cells modified by basic fibroblast growth factor on injured spinal cord in rats

Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.Methods Two hundred and

ZXDC基因敲减对脊髓神经元氧化应激损伤的保护作用

目的 探讨转录因子ZXDC基因敲减对脊髓神经元(SCNs)氧化应激损伤后的保护作用及机制。方法 应用不同浓度H_(2)O_(2)诱导SCNs氧化应激损伤,CCK8检测细胞活性筛选H_(2)O_(2)诱导最佳浓度;实验细胞分为:Control组、H_(2)O_(2)+AAV-NC组和H_(2)O_(2)+AAV-ZXDC siRNA组,免疫荧光染色鉴定原代SCNs,检测各组ZXDC表达和神经突起平均长度;Western bolt检测各组细胞中ZXDC、CCL2、CCR2表达,qRT-PCR检测细胞中炎症因子TNF-α和IL-1β m RNA表达,应用EdU荧光染色、CCK8检测ZXDC对SCNs增殖和活性的影响。结果 筛选600μmol/L H_(2)O_(2)适用于SCNs氧化应激模型制备。β-Ⅲ-tubulin免疫荧光染色鉴定原代SCNs培养成功;与Control组比较,H_(2)O_(2)+AAV-NC组神经突起平均长度显著降低,ZXDC、CCL2和CCR2表达显著增高,而H_(2)O_(2)+AAV-ZXDC siRNA组较H_(2)O_(2)+AAV-NC组神经突起平均长度显著增高,ZXDC、CCL2和CCR2蛋白表达显著降低(P<0.05);与Control组比较,H_(2)O_(2)诱导组TNF-α和IL-1β m RNA相对表达显著增高,细胞增殖和细胞活力显著降低。与H_(2)O_(2)+AAV-NC组比较,H_(2)O_(2)+AAV-ZXDC si RNA组TNF-α和IL-1β m RNA相对表达显著降低,细胞增殖和细胞活力显著增高(P<0.05)。结论 ZXDC基因敲减通过调控CCL2/CCR2信号通路促进氧化应激损伤SCNs细胞增殖、细胞活力和神经突生长。

REEXPRESSION OF NERVE GROWTH FACTOR RECEPTOR IN HUMAN TRAUMATIC INJURED SPINAL CORD

In this study, the reexpression of nerve growth factor receptor (NGFR) on paraffin sections of the human spinal cord was examined with immunohistochemical method in 18 cases with survival periods of 2 hours to 28 months after trauma. The results were as follow: the reexpression of NGFR in motoneurons of the ventral horn began on the fourth day after trauma and decreased within 30 days after trauma. However, it could still be observed in patients who survived up to 28 months. The axons in funiculus dorsalis reexpressed NGFR 7 hours to 9 weeks after injury, which may be interpreted as axoplasmic transport effect of NGFR in the spinal ganglion cells. NGFR labelled intraspinal microvessels were present in the injured spinal cord. Reexpression of NGFR in motoneurons after injury reflects an increased demand of neurotrophic factors, and an increased access exerting the physiological effects of trophic factors mediated by NGFR.

美国脊髓损伤协会损伤分级与脊髓运动损伤程度的相关性研究

目的:探讨和比较美国脊髓损伤协会(ASIA)损伤分级与脊髓运动损伤程度的关系。方法:对43例脊髓损伤患者分别进行ASIA损伤分级、按肢体运动功能分级和ASIA运动评分,比较分级结果,并对ASIA损伤分级、按肢体运动功能分级和ASIA运动评分间的关系作等级相关分析。结果:ASIA-A级(完全性脊髓损伤)患者的按肢体运动功能分级存在差异。ASIA损伤分级与按肢体运动功能分级及ASIA运动评分的等级相关系数为0.578—0.809(P<0.01),而按肢体运动功能分级与ASIA运动评分的等级相关系数为0.970—0.999(P<0.01),相关程度存在差异。结论:ASIA损伤分级不能够完全反映脊髓运动损伤水平。

妙纳治疗脊髓损伤后痉挛性膀胱功能障碍的临床观察

目的 :观察妙纳治疗脊髓损伤 (SCI)后痉挛性膀胱功能障碍的临床效果。方法 :34例SCI后痉挛性膀胱功能障碍的患者于服药前和服药后观察膀胱贮尿功能的变化 ,并进行膀胱压力 -容积检测比较。结果 :妙纳治疗后 ,每次排尿量和排尿间隔时间均较用药前明显增加 (P <0 .0 1 ) ,膀胱容量、膀胱壁顺应性等指标较用药前也明显增加 (P <0 .0 1 )。结论 :妙纳治疗SCI后痉挛性膀胱功能障碍时可改善膀胱的贮尿功能 ,可作为痉挛性膀胱功能障碍药物治疗的又一选择。

阿夫唑嗪用于脊髓损伤患者膀胱训练的疗效观察

目的探讨α1受体阻滞剂辅助脊髓损伤患者膀胱训练的作用及局限性。方法 70例患者分为两组 ,分别采用间歇导尿、间歇导尿并口服阿夫唑嗪的方法 ,以治疗后残余尿量降低至可以停止间歇导尿或减少间歇导尿次数为有效 ,4个月后观察疗效并加以比较。结果间歇导尿组和间歇导尿加口服阿夫唑嗪组膀胱训练的效果无显著性差异 ;达到有效的时间相比无显著性差异。结论在膀胱训练中 ,阿夫唑嗪加间歇导尿的方法并不比单纯间歇导尿的方法优越。

心理干预配合功能训练对脊髓损伤患者康复的疗效观察

目的探讨心理干预配合功能训练对脊髓损伤患者康复的疗效观察。方法 82例脊髓损伤住院患者随机分为心理干预组和对照组。对照组采用常规综合康复治疗;心理干预组在采用综合康复治疗的基础上加用心理干预。治疗前后对两组临床疗效进行比较,评定指标采用Barthel指数、功能独立性评定(FIM)。结果与治疗前比较,心理干预组和对照组患者在治疗后的Barthel指数、FIM评分均有显著提高,但治疗后心理干预组的Barthel指数、FIM评分高于对照组,且差异有统计学意义(P<0.05)。结论心理干预配合功能训练有利于脊髓损伤患者日常生活活动能力及自立能力的改善。

白藜芦醇对大鼠急性脊髓损伤后运动功能及细胞凋亡的影响

目的探讨白藜芦醇(Res)对大鼠急性脊髓损伤后运动功能、组织病理学及神经细胞凋亡的影响。方法本文采用Allen′s脊髓打击模型,将24只SD大鼠,随机分为3组,每组8只。A组:假手术组;B组:脊髓打击伤组;C组:Res处理组。术后分别观察24 h4、8 h、72 h BBB评分变化;72 h处死动物取材,HE、Nissl染色观察脊髓组织病理学变化;原位末端脱氧核糖核苷酸转移酶介导dUTP标记技术检测神经细胞凋亡情况。结果BBB评分提示3个时相点均有所改善,且C组均高于B组,呈显著性差异(P<0.05);组织病理组织切片观察显示C组结构破坏明显轻于B组;TUNEL阳性神经细胞均有表达,C组明显少于B组。结论Res能明显促使脊髓损伤后的大鼠后肢的神经运动功能恢复,保护神经结构破坏和抑制神经细胞凋亡。

脊髓损伤继发骨质疏松动物模型骨力学性质实验研究

目的研究正常大鼠骨和脊髓损伤所致大鼠骨质疏松骨力学性质，为临床提供生物力学参数。方法选用280-320g，4-5月龄wistar雄性大鼠77只，随机分为0周空白对照组11只，3周对照组11只，7周对照组11只，11周对照组11只，三周实验组11只，7周实验组11只，11周实验组11只。0周空白组于0周处死，解剖取大鼠股骨、胫骨、肱骨，以生理盐水浸温的纱布包裹，置-20℃冰箱内保存备用。对3、7、11周对照组大鼠以咬骨钳将其椎板咬开，不破坏硬膜和脊髓，人为造成脊髓损伤后饲养，复制骨质疏松模型。分别于3、7、11周处死对照组和实验组大鼠。取大鼠股骨进行压缩实验，取肱骨进行剪切实验，取胫骨进行扭转实验。结果得出了各组大鼠股骨压缩力学性能指标、肱骨剪切力学性能指标和胫骨扭转力学性能指标。结论实验组和对照组的各项力学性能指标显著低于0周空白组（P〈0．05）。

无脊髓损伤的严重下颈椎骨折脱位的手术治疗

目的探讨无脊髓损伤的严重下颈椎骨折脱位的手术治疗方法。方法对21例牵引复位失败的无脊髓损伤的严重下颈椎骨折脱位患者,首先俯卧位后路切开复位,短节段的侧块螺钉或棘突间钢丝固定;陈旧骨折脱位,需行脱位小关节的上关节突部分切除及黄韧带切除,不固定。然后再行前路切开椎体减压,髂骨植骨或钛网植骨钢板内固定。术后一周带颈托下地行走。结果本组21例脱位完全复位,无脊髓损伤发生,随访8～24个月,平均16月,植骨完全融合,无假关节、骨不连发生,颈椎椎间高度、生理曲度及颈椎稳定性维持良好。结论对于无脊髓损伤的下颈椎骨折脱位宜采用一期前后路联合手术切开复位内固定,最大限度保留活动节段,恢复颈椎椎间高度和生理曲度,重建颈椎即刻稳定性,对防止继发性脊髓损伤有极其重要的作用。

脊髓损伤后bFGF和GFAP的变化及其意义

目的 研究脊髓损伤后碱性成纤维细胞因子和胶质纤维酸性蛋白的变化及其两者的相关性 ,探讨脊髓损伤后脊髓的自身保护机制以及星形胶质细胞在脊髓损伤中的作用。方法 用免疫组织化学、组织学染色和图象分析的方法检测损伤脊髓碱性成纤维细胞及胶质纤维酸性蛋白表达的动态变化。结果 脊髓损伤后 1d损伤脊髓中碱性成纤维细胞的表达明显增高 ,7d达到高峰 ,14d末回落 ;而胶质纤维酸性蛋白表达则在 1～ 14d内呈进行性增高趋势。两指标相关性显著 (r =0 .777,P =0 .0 0 1)。结论 脊髓损伤后反应性星形细胞胶质化对脊髓的再生和自身修复起着重要作用 ,提示脊髓本身存在自身保护机制。

中重度颅脑损伤合并颈椎损伤38例诊治体会

目的探讨中重度颅脑损伤合并颈椎损伤的临床特点,总结治疗体会。方法回顾性分析38例中重度颅脑损伤合并颈椎损伤的临床诊断和影像学检查资料。结果所有患者均行头颅CT及颈椎CT检查,29例患者行颈髓MRI检查;头颅CT均有异常发现,颈椎CT异常33例;颈椎CT正常,颈髓MRI异常5例。结论中重度颅脑损伤合并颈椎损伤的患者可在行头颅CT检查的同时行颈椎CT检查并及时行颈髓MRI检查,尽早明确诊断,以免不当护理造成进一步颈椎或颈髓的损伤,同时又能明确无放射影像异常的颈髓损伤。

脊髓损伤继发骨质疏松动物模型骨压缩应力松弛蠕变测试

研究正常大鼠骨和脊髓损伤所致大鼠骨质疏松骨的力学性质,为临床提供粘弹性力学参数。选用280～320g 4～5月龄wistar雄性大鼠44只,随机分为0周空白对照组11只,3周实验组11只,7周实验组11只,11周实验组11只,0周空白组于0周处死,解剖取大鼠股骨,以生理盐水浸湿的纱布包裹,置-20℃冰箱内保存备用。对3、7、11周实验组大鼠人为造成脊髓损伤后饲养,复制骨质疏松模型。分别于3、7、11周处死实验组大鼠,解剖取大鼠股骨。对0周空白组、3周实验组、7周实验组、11周实验组大鼠股骨进行压缩应力松弛、蠕变实验。结果得出了各组大鼠股骨压缩应力松驰函数、蠕变函数及曲线。实验组的各项力学性能指标显著低于0周空白组(P<0.05)。

脊髓损伤患者家属配合功能训练的疗效观察

目的研究脊髓损伤患者家属配合功能训练对脊髓损伤患者日常生活、活动能力(ADL)及功能独立性的影响。方法80例脊髓损伤住院患者随机分成两组,治疗组除常规康复治疗外,教会患者家属脊髓损伤患者共性的康复方案,让患者家属在常规康复治疗时间外每天给患者多2h的训练;出院后定期随访,做好患者家属的功能训练方法指导;对照组仅进行常规康复治疗,出院后自行进行功能训练。分别于入院时、住院2个月、出院3个月对两组进行评定。评定指标采用Barthel指数、功能独立性评定(FIM)。结果2个月出院时两组的ADL、功能独立性均有改善。出院3个月后治疗组患者的日常生活、活动能力、功能独立性较出院时明显提高,对照组无明显改善,差异有统计学意义(P<0.05)。结论教会患者家属易懂可行且通用的康复技术有利于脊髓损伤患者ADL及功能独立性的改善。