脊髓挤压伤所致小胶质细胞的变化与血脊髓屏障的关系

为探讨脊髓损伤时血脊髓屏障的破坏和小胶质细胞被激活两者之间的关系,本实验用大鼠脊髓挤压伤模型进行了研究。将成年雄性SD大鼠64只,随机分为对照组及脊髓挤压伤后0h、8h、24h、72h、1w、2w、4w等8组。分别以HE染色观察病理变化,小胶质特异性标记物OX-42的免疫荧光组化染色观察小胶质细胞,股静脉伊文思蓝注射观察血脊髓屏障的变化。结果显示,脊髓损伤面积在伤后8h组明显扩大,72h达顶峰,1w组时面积回缩并维持到实验最后(4w)。在伤后24h组可观察到活化的小胶质细胞,其后一部分迁移入损伤区内,吞噬坏死组织,变成巨噬细胞。至4w时,HE染色切片上仍可在伤区内见到小胶质巨噬细胞。伤区外活化的小胶质细胞仍可见于伤后4w。伊文思蓝不能通过正常的血脊髓屏障,脊髓挤压伤后即可进入脊髓,分布于损伤区及其邻近。至1w时脊髓内已无伊文思蓝,血脊髓屏障恢复正常。此现象与脊髓伤后活化的小胶质细胞长期存在的事实不一致。活化的小胶质细胞可损坏血脊髓屏障,血脊髓屏障在脊髓挤压伤后1w已恢复,而活化的小胶质细胞却可在伤后长期存在,说明单纯激活的小胶质细胞不足以破坏血脊髓屏障。     

大鼠颈椎骨折错位致脊髓损伤模型的继发性损伤研究

目的　建立大鼠颈椎骨折错位致脊髓继发性损伤模型。 方法　20只成年SD大鼠,随机分为实验组(n=11)和对照组(n=6),3只处死取颈椎测量C4/5水平椎管和椎体矢状径。实验组利用颈椎骨折错位脊髓损伤装置在C4/5之间快速（200 mm/s）错位1.65 mm,造成颈椎骨折错位和颈脊髓损伤,采用自制器械固定颈椎。对照组除未行错位外与实验组相同。术后进行行为学（前肢运动和梳理试验）评价8周,和病理学检查。 结果 实验组行为学评分各个观察时间点均较对照组低。脊髓HE染色切片见实验组脊髓萎缩,灰质破坏,空洞,对照组未见明显异常。实验组损伤中心残留面积（2.79±0.98）mm2,明显小于对照组（6.36±0.08）mm2（P=0.034）。 结论　成功建立了大鼠颈椎骨折错位脊髓继发性损伤模型,大鼠C4/5骨折错位1.65 mm导致明显的脊髓组织损伤和运动功能障碍。     

下颈椎骨折脱位合并脊髓损伤早期急救治疗对预后的影响

目的探讨下颈椎骨折脱位合并脊髓损伤的早期治疗方法和护理注意事项及其对预后的影响。方法回顾性分析183例伤后3 d内入院的颈椎骨折脱位合并脊髓损伤患者,其中男性120例,女性63例;年龄17~81岁,平均年龄36.5岁。入院时间均在受伤后3d内,平均26h(2~68h),所有患者均发生不同程度四肢瘫痪,按照Frankel分级:A级95例,B级28例,C级20例,D级40例。脊髓损伤水平:C23例,C311例,C429例,C584例,C637例,C719例。受伤类型:高处坠落伤21例,车祸伤162例。结果日本骨科学会(JOA)评分术前(4.2±1.8)分,术后1周(7.9±2.2)分,末次随访(10.0±2.0)分。术后1周、末次随访与术前比较差异均有显著统计学意义(P0.01)。8 h内行甲强龙冲击治疗65例,行早期气管切开38例,行前路手术110例,后路手术42例,前后路联合手术31例。死亡3例,低蛋白血症20例,肺感染6例,深静脉血栓2例。结论早期正确的治疗措施可有效提高颈椎骨折脱位合并脊髓损伤的疗效,降低其并发症的发生。     

Delayed post‐injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice

The activation of a complement system can aggravate the secondary injury after spinal cord injury (SCI). However, it was reported recently that the activation of a complement could have both a secondary injury and a neuroprotective effect, in which C5a is the most important factor, but there is no direct evidence for this dual effect of C5a after SCI. In order to investigate the potential neuroprotective effect of C5a after SCI, in this study ectogenic C5a was injected intraperitoneally before/after SCI in vivo, or administrated to mechanically injured neurones in vitro; following this, neurone apoptosis, neurite outgrowth, axonal regeneration and functional recovery were investigated. The in‐vivo experiments indicated that, following treatment with C5a 24 h before or immediately after injury, locomotor function was impaired significantly. However, when treatment with C5a took place 24 h after injury, locomotor function improved significantly. In‐vitro experiments indicated that a certain concentration of C5a (50–100 nM) could inhibit caspase‐3‐mediated neurone apoptosis by binding to its receptor CD88, and that it could even promote the neurite outgrowth of uninjured neurones. In conclusion, delayed post‐injury administration of C5a within a certain concentration could exert its neuroprotective effect through inhibiting caspase‐3‐mediated neurone apoptosis and promoting neurite outgrowth of uninjured neurones as well. These data suggest that C5a may have opposite functions in a time‐ and concentration‐dependent manner after SCI. The dual roles of C5a have to be taken into account when measures are taken to inhibit complement activation in order to promote regeneration after SCI.     

Effect of cyclosporin A on functional recovery in the spinal cord following contusion injury

Considerable evidence has shown that the immunosuppressant drug cyclosporin A (CsA) may have neuroprotective properties which can be exploited in the treatment of spinal cord injury. The aim of this study was to investigate the cellular environment within the spinal cord following injury and determine whether CsA has an effect on altering cellular interactions to promote a growth-permissive environment. CsA was administered to a group of rats 4 days after they endured a moderate contusion injury. Functional recovery was assessed using the Basso Beattie Bresnahan (BBB) locomotor rating scale at 3, 5 and 7 weeks post-injury. The rats were sacrificed 3 and 7 weeks post-injury and the spinal cords were sectioned, stained using histological and immunohistochemical methods and analysed. Using stereology, the lesion size and cellular environment in the CsA-treated and control groups was examined. Little difference in lesion volume was observed between the two groups. An improvement in functional recovery was observed within CsA-treated animals at 3 weeks. Although we did not see significant reduction in tissue damage, there were some notable differences in the proportion of individual cells contributing to the lesion. CsA administration may be used as a technique to control the cell population of the lesion, making it more permissive to neuronal regeneration once the ideal environment for regeneration and the effects of CsA administration at different time points post-injury have been identified.     

川芎嗪促进脊髓损伤修复的研究进展

川芎嗪应用于临床治疗心脑血管疾病、呼吸系统疾病、肾脏疾病和肝硬化等疾病已有多年,对治疗脊髓损伤（spinal cord injury,SCI）的相关研究也逐年增多。近年来,关于川芎嗪治疗脊髓损伤的临床试验和动物实验不断增多,主要机制包括抑制细胞凋亡和炎症反应、降低内皮素含量、改变血液流变学、增加神经丝蛋白和神经营养因子表达、保护线粒体和改善细胞内外离子紊乱。     

Nontumor lesions of spinal cord and spine

Nontumor lesions of the spinal cord and spine include developmental disorders, cystic tumor-like lesions, vascular disorders, infective diseases, demyelinating diseases, degenerative diseases, metabolic and toxic disorders, and spinal cord injury. In addition, diseases of the spine and extradural spaces secondarily cause spinal cord injury. Aside from tumors, these include developmental abnormalities, inflammatory diseases, nontumor space-occupying lesions, and tumor-like lesions such as lipomas, vascular malformations, and cysts. Awareness is required of hemostatic agents used during surgery and subsequently presenting as space-occupying lesions, which have to be differentiated from recurrent lesions. On the therapeutic front, stem cell transplantation into spinal cord for treatment of neurodegenerative disorders, spinal cord injury, and multiple sclerosis is a challenging prospect.     

临床相关的脊髓损伤动物模型新进展

自1911年首个脊髓损伤动物模型建立以来,相继出现切割损伤型、牵拉损伤型、压迫损伤型和缺血损伤型等模拟临床不同环境的脊髓损伤动物模型。迄今,这些模型在建立过程中不断融入许多新技术:计算机控制的精确打击、定位下的精准切割,数字化的牵拉器及符合生物力学的脊髓压迫器等。科学技术的发展促进了脊髓损伤动物模型更加贴近不同的临床状态。     

大鼠新型挫伤型脊髓损伤模型的建立及评价

目的:制备新型挫伤型脊髓损伤大鼠模型,通过行为学评分和形态学方法进行评价,为进一步研究脊髓损伤的机制及早期治疗提供依据。方法:SD大鼠随机分为对照组和实验组,对照组(A组)采用改良的Allen法制备急性脊髓挫伤模型,实验组在打击的基础上分别受压3s(B组)、5s(C组)和10s(D组),制备新型挫伤型脊髓损伤模型;各组分别于术后1、3、7、14、21d观察其行为学评分和病理学改变;免疫组织化学方法检测促炎因子高迁移率族蛋白B1(HMGB1)在各组不同时间点的表达变化。结果:实验组各时间点BBB评分和损伤程度与对照组比较均有显著差异(P0.05),其中A组和B组术后损伤程度差别微小;C组后肢运动功能障碍明显,脊髓损伤区域出现典型的病理改变;D组损伤最严重,死亡率高。HMGB1表达以损伤C组为典型代表,术后阳性表达明显增多,第3d达高峰,主要表达部位为神经元胞浆和神经胶质细胞核内。结论:采用改良Allen法打击再受压5s制备的脊髓损伤模型能很好地模拟临床实际,且稳定性高、可复制性好,为一种新型挫伤型脊髓损伤模型。     

The Effects of Age on the Morphometry of the Cervical Spinal Cord and Spinal Column in Adult Rats: An MRI‐Based Study

Rat models are commonly used to investigate the pathophysiological pathways and treatment outcomes after spinal cord injury (SCI). The high incidence of fall‐induced SCI in older adults has created a need for aging models of SCI in rats to investigate potential age‐related differences in SCI severity and outcomes. The aims of this study were to determine the influences of age and vertebral level on the geometries of the cervical spinal cord and spinal column in a rat model. Three young (3 months) and three aged (12 months) Fischer 344 rats were imaged in a high field (7 T) small‐animal magnetic resonance imaging system. All spinal cord geometry variables (including depth, width, and axial cross‐sectional area) and one spinal canal variable (depth) were significantly larger in the aged specimens by an average of 8.1%. There were main effects of vertebral level on all spinal cord variables and four spinal canal variables with values generally larger at C4 as compared to C6 (average increases ranged from 5.7% to 12.9% in spinal cord measures and 5.4% to 6.8% in spinal canal measures). High inter‐rater reliability between two measurers was observed with a mean intraclass correlation of 0.921 and percent difference of 0.9% across all variables measured. This study clearly demonstrates that cervical spinal cord geometry changes between the ages of 3 and 12 months in Fischer 344 rats. This information can aid in the planning and interpretation of studies that use a rat model to investigate the influence of age on cervical SCI. Anat Rec, 297:1885–1895, 2014. © 2014 Wiley Periodicals, Inc.     

基于体素的形态学分析在脊髓损伤中的研究进展

创伤性脊髓损伤（SCI）通常会导致大脑皮质发生继发性损害,造成神经元凋亡或萎缩。基于体素的形态学（VBM） 技术凭借其无创性、精确性的优点,已在SCI患者大脑微观结构变化的研究中得到了广泛应用。本文主要从损伤后皮质 萎缩情况及其与患者临床表现间相关性的横向研究结果,损伤早期进行性神经退变的时空模式及其对患者临床结果预测 能力的纵向研究结果,损伤持续时间（亚急性、慢性等）、损伤严重程度（完全性、不完全性等）、临床康复情况（感觉运动功 能、神经性疼痛等）等因素对研究结果的不同影响这3个方面对VBM在SCI中的研究进展进行综述,并指出未来研究应进 一步提高VBM技术的可靠性,同时完善研究方案的设计,以促进VBM在脑功能探索和SCI康复治疗中的作用。     

大鼠脊髓损伤后植入人发角蛋白的实验研究

目的：研究人发角蛋白（HHK）在脊髓损伤（SCI）修复中诱导和促进神经元和神经纤维的再生以及HHK在脊髓中的降解机理。方法：选用12只成年雌性SD大鼠,采用改制的II型NYU装置,建立SCI组,SCI后植入HHK组,并设正常对照组,分别于术后14d取材,经HE,Mallory's－磷钨酸－苏木素,Loyer'sSterry Thionin等方法染色,观察其光镜结构的变化。结果：与损伤组相比较,植入HHK组损伤节段的萎缩程度明显,然质中部分神经元残存,有髓神经纤维脱髓鞘现象减轻,HHK周边集聚大量巨噬细胞和胶质细胞,植入的HHK毛小皮膨胀松弛,出现与皮质层分离,皮质层内出现皲裂,中央髓质腔增大,结论：植入HHK具有减轻脊髓损伤后的继发性损伤的作用,为进一步研究HHK在SCI修复过程中的作用及机理提供了形态学基础。     

脑红蛋白在脊髓缺血再灌注损伤中的表达及其意义

目的:观察大鼠脊髓缺血再灌注损伤(SCI)过程中脑红蛋白(Ngb)的表达变化及其意义。方法:健康成年Wistar大鼠随机分为脊髓压迫缺血再灌注组和假手术对照组。运用原位杂交组织化学和免疫印迹法,检测压迫段脊髓组织中Ngb的表达变化。结果:再灌注2h后,Ngb在压迫段脊髓开始表达上调,24h较为明显,48h达峰值,72h表达减少,与假手术组相比较,具有显著性差异。免疫印迹法的结果和上述结果一致。结论:在脊髓缺血再灌注损伤中Ngb的表达变化与再灌注时间相关,其表达上调是机体内源性神经保护之一。     

电刺激排尿中圆锥部完全性骶部去传入的解剖学研究

目的:为从脊髓圆锥部进行完全性骶部去传入手术提供解剖基础。方法:解剖１０具成人脊柱脊髓标本,测量圆锥终末点至不同骶髓节段的距离。结果:脊髓圆锥长约３ｃｍ,位于Ｔ１２至Ｌ１椎体水平。从圆锥终末点Ｓ３和Ｓ２节段的长度分别为(１５．９±２．３)ｍｍ和(２１．６±２．７)ｍｍ。结论:在电刺激排尿时,切除圆锥终末背侧最远段２５ｍｍ的后根根丝,可完全切断Ｓ２及其以下的骶部传入纤维,获得彻底的膀胱去传入效果。     

下颈椎爆裂骨折合并脊髓损伤的手术治疗

目的评估手术治疗下颈椎爆裂骨折合并脊髓损伤的临床效果。方法回顾性分析自2002年以来收治的12例下颈椎爆裂骨折合并脊髓损伤的临床资料。伤后2~8 d,4例采用前路减压植骨融合内固定术,8例采用1期前-后联合减压植骨融合内固定术。采用ASIA分级评估神经功能,用放射学方法评估植骨融合情况,记录围手术期并发症。结果平均随访11.2个月。1例伤后2 d接受手术,术后死亡,6例术后发生并发症,经对症处理治愈。3例术后需要机械通气支持。7例患者有不同程度神经功能恢复（ASIA分级提高1~2级）。随访期间未见内固定失败者。结论手术治疗下颈椎爆裂骨折可以达到神经组织减压和重建颈椎稳定性的目的 ,根据具体病情可以选择单纯前路手术或者1期前后路联合手术。     

急性钳夹型脊髓损伤模型大鼠造模方式的选择:一项网状Meta分析

目的:用动脉瘤夹创建急性钳夹型脊髓损伤模型是一种简单有效的造模方法.然而,为了建立这种急性钳夹型脊髓损伤动物模型,许多实验根据不同闭合力的动脉瘤夹和压迫时间采用了不同的造模方式,其中包括30 g压迫力的动脉瘤夹压迫脊髓60 s(30 g,60 s组);70 g压迫力的动脉瘤夹压迫脊髓30 s(70 g,30 s组);7...     

颈脊髓损伤致尿崩症、低钠血症的临床分析

目的探讨颈脊髓损伤致尿崩症、低钠血症的机理及临床治疗经验。方法对2003年5月至2007年8月收治的6例颈脊髓损伤并发尿崩症、低钠血症患者的临床资料进行回顾分析。结果5例经治疗后尿崩症、低钠血症得到明显缓解，1例自动放弃治疗。结论颈脊髓损伤并发尿崩症、低钠血症的原因是多方面的，治疗应限制水摄入、补充钠盐。     

The neuroprotective effects of fibronectin mats and fibronectin peptides following spinal cord injury in the rat

We have shown previously that mats made from the glycoprotein fibronectin are permissive for axonal growth when implanted into the injured spinal cord. Recent evidence has indicated that fibronectin and its peptides also have neuroprotective effects in the CNS. We have therefore examined the neuroprotective effects of fibronectin applied to a spinal cord injury site. Adult rats with fibronectin mats implanted into a spinal cord lesion cavity had decreased apoptosis in the intact adjoining spinal cord tissue at 1 and 3 days post-injury compared to rats that had gelfoam implanted into the lesion cavity. Rats with fibronectin mat implants also showed enhanced hindlimb locomotor performance for the first 3 weeks post-surgery compared to control animals. To further examine the neuroprotective potential of fibronectin following spinal cord injury, we examined the effects of placing fibronectin mats over the site of a spinal cord hemisection or of delivering a solution derived from a dissolved fibronectin mat. The effects of these treatments were compared with control animals and animals that were treated with a fibronectin peptide (PRARIY) that has been shown to decrease secondary damage in a rodent model of cerebral ischemia. Results showed that both types of fibronectin mat treatment resulted in decreased lesion size, apoptosis, and axonal damage within the first week post-injury compared to control animals and were comparable in their neuroprotective efficacy to treatment with the fibronectin peptide. The results of the current study indicate that fibronectin based biomaterials have neuroprotective effects following spinal cord injury, in addition to their previously reported ability to promote axonal regeneration.     

Shh/Gli1信号参与小鼠脊髓损伤后血-脊髓屏障渗透性改变及运动功能恢复

目的:探讨sonic hedgehog/Gli1(Shh/Gli1)信号在小鼠脊髓损伤后病理变化及运动功能恢复中的作用。方法:成年雄性C57野生型、Gli1lz和Gli1lz/lz小鼠行T8节段脊髓夹伤及假手术。Gli1lz小鼠脊髓损伤及假手术后3 d行X-gal染色;7 d行Shh/PDGFr-α、Shh/GFAP、LacZ/GFAP染色,观察Shh/Gli1信号在小鼠脊髓损伤后的激活。C57野生型和Gli1lz/lz小鼠脊髓夹伤后7 d行GFAP染色和实时定量RT-PCR,观察星形胶质细胞反应;术后14 d尾静脉注射伊文氏兰观察血-脊髓屏障改变;术后1、3、5 d和7 d行BMS评分评价小鼠后肢运动功能。结果:脊髓损伤7 d后,损伤区Shh表达升高;Shh/Gli1信号报告基因LacZ表达升高,主要表达于反应性星形胶质细胞;免疫组织化学及实时定量RT-PCR结果显示Gli1基因敲除不影响脊髓损伤后GFAP表达;伊文氏兰染色及其定量分析显示Gli1lz/lz小鼠脊髓损伤后脊髓组织伊文氏兰外渗增加。BMS评分显示Gli1lz/lz小鼠运动功能恢复显著差于野生型小鼠。结论:Shh/Gli1信号在小鼠脊髓损伤后激活,可能参与脊髓损伤后血-脊髓屏障渗透性的改变,并影响脊髓损伤后的运动功能恢复。