马尾神经压迫损害发病机制的初步研究
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摘要
研究背景:
随着医学的进步,人们对疾病认识程度的加深,马尾神经压迫损害(Cauda equina compression,CEC)及由此导致的马尾神经综合征(Cauda equina syndrome, CES)愈来愈引起学者们的重视。据统计,普通人群中CES的发病率为1:100,000到1:33,000之间,患有下腰痛的人群中CES发病率为万分之4,而在患有腰椎间盘突出的患者中,CES发病率更是达到了1%～10%。我国近30%的腰椎疾患的患者存在不同程度的CEC症状。马尾神经压迫损害及其继发性病理生理反应可直接导致组织器官神经功能损伤及功能障碍,导致下肢疼痛、运动感觉功能、大小便功能及性功能障碍,且其治疗困难,致残率非常高,给患者本人造成了极大的痛苦,也给家庭和社会带来沉重的负担。目前对CEC的研究相对较少而且缓慢,预后难以预料,主要是该病的病理生理机制非常复杂,对此认识还不够全面、深入。以往研究显示,马尾神经压迫损害致神经元的凋亡是造成马尾神经压迫临床症状的重要原因,但究竟是哪些基因参与了马尾神经压迫损害导致的神经元的凋亡尚不清楚。国内外近年研究显示,马尾神经压迫损伤后,其局部病理改变如不能得到及时改善,则形成恶性循环,由马尾神经的局部损害到广泛性病理损害,可产生顺行性、逆行性变性及传递性神经元变性,以至于产生跨细胞的中枢神经元变性,而致使其结构和功能难以修复,造成永久性的功能损害。在此实验基础上,本课题拟通过建立实验性大鼠马尾神经压迫模型,就马尾神经压迫损害的基础进行初步探讨。
第一部分:马尾神经压迫动物模型的建立及马尾神经压迫电生理的实验研究
目的:对SD大鼠腰椎区域相关组织解剖行初步观测,建立合适的马尾神经压迫损害动物模型,并在此基础上进行实验性大鼠急性马尾神经压迫后行为学、神经电生理及组织学研究。
方法:首先对SD大鼠腰椎区域相关组织解剖做了初步观测,得到SD大鼠腰椎区域相关解剖数据,根据测量数据制作改良的实验性大鼠急性马尾神经压迫动物模型。之后将实验动物随机分为以下4组:CON组:空白对照组(n=8);SHAM组:假手术组(n=8);CCC组:经典马尾神经压迫组(n=8);MCC组:改良马尾神经压迫组(n=9)。手术建立改良的实验性大鼠急性马尾神经压迫动物模型:显露L4～L5的椎板,扩大L4/5椎间隙,切除L4/5间隙的黄韧带,向尾端塞入10.0×1.0×(1.1-1.3)mm硅胶条1根。并与经典实验性大鼠急性马尾神经压迫动物模型进行比较。术后第1、3、7、14、28天对此模型进行了行为学评价,包括:BBB评分、电子von Frey机械测痛法测定大鼠缩足潜伏期、热板实验、甩尾实验、步行分析。结合HE染色及尼氏染色,光镜下对实验性大鼠急性马尾神经压迫模型进行组织病理学评价。在此基础上,使用诱发电位记录仪,进行了脊髓诱发电位(SCEP)N1波潜伏期及运动神经传导速度(MNCV)的动态测定,了解实验性大鼠急性马尾神经压迫后电生理的动态变化。
结果:模型制作大鼠死亡率低。步行分析强迫运动评价显示,模型组大鼠术后出现明显神经源性间歇性跛行,并且持续稳定,CON组与SHAM相比无明显差异;CCC组及MCC组相比无明显差异。BBB评分显示,与对照组相比,模型组术后静态运动功能减退不明显,非强迫运动功能术后恢复较早;相关感觉行为指标评价出现了明显感觉障碍,主要表现为痛觉及热觉减退,以术后早期明显,随着时间延长,感觉功能逐渐恢复,但未恢复到术前水平。通过对压迫DRG(DRG)、马尾神经(CE)及脊髓、圆锥的大体观、组织病理学的动态观察,可见神经根压迫后其有髓神经纤维数目减少和组织结构的改变,如神经膜细胞胞质肿胀和细胞水肿、尼氏体减少、华勒变性、神经元轴突脱髓鞘变等。电生理研究发现,马尾神经受压后SCEP发生的变化明显,潜伏期明显延长,至术后14天仍不能完全恢复;MNCV的下降恢复较快,术后7天即恢复到术前水平。
结论:本部分实验结果说明,改良的实验性大鼠急性马尾神经压迫模型可以复制出神经源性间歇性跛行,且更接近于椎管狭窄对马尾神经的压迫,为临床马尾神经压迫导致的疼痛及麻木治疗的研究建立了可供参考的动物模型。行为学评价说明,马尾神经压迫性损伤后,出现感觉功能障碍,且随着时间延长,神经功能有所恢复,但由于压迫因素未解除,神经功能不能恢复到术前水平。电生理实验研究说明马尾神经感觉支对机械压迫的反应比较敏感,而运动支相对则较容易恢复。
第二部分:马尾神经压迫后DRG、马尾神经与相应脊髓神经细胞凋亡及PUMA的表达
目的:研究马尾神经压迫后DRG、马尾神经与相应脊髓神经细胞有无凋亡的发生;了解马尾神经压迫后是否导致PUMA表达的变化以及表达数量随时间的变化,为手术时机的选择提供依据,以及为手术的疗效提供评价标准。
方法:将50只SD大鼠随机分为下列几组:A组:空白对照组(n=10);B组:马尾神经压迫1d组(n=8);C组:马尾神经压迫3d组(n=8);D组:马尾神经压迫7d组(n=8);E组:马尾神经压迫14d组(n=8);F组:马尾神经压迫28d组(n=8)。用免疫组织化学的方法检测DRG、马尾神经与相应脊髓中PUMA的表达。具体如下:4%的多聚甲醛灌注固定大鼠,取出标本,经石蜡包埋后切片,厚度在4μm。二甲苯脱蜡后,经梯度乙醇至水和TBS冲洗,用3%过氧化氢封闭内源性过氧化酶约5分钟,加入0.01M柠檬酸缓冲液(pH6.0),煮沸20分钟,再用5-10%山羊血清室温封闭20分钟。一抗孵育1h小时和二抗孵育30分钟后,用DAB显色处理,最后经TBS冲洗,苏木素复染和二甲苯透明后,用中性树胶封片。
用末端转移酶介导的dUTP缺口末端标记(Tunel)法检测DRG、马尾神经与相应脊髓中细胞凋亡:4μm石蜡切片常规脱蜡至水,3%过氧化氢封闭,蛋白酶K处理后置入Tunel混合液,37℃,1h,Streptavidin-HRP 30min后,0.04% DAB+0.03%H2O2显色10min,苏木素衬染和二甲苯透明后,常规树脂封片。
采用实时定量PCR技术检测DRG、马尾神经与相应脊髓中PUMA基因mRNA的表达水平:TRIzol法抽提细胞总RNA,RNA的鉴定及定量,逆转录至cDNA,引物设计与合成,BLAST确认引物特异性,测定各样品的Ct值,以β-actin浓度为参照对待测样品的Ct值进行校正。
结果:免疫组化结果示对照组未见明显PUMA阳性深染区。当大鼠马尾神经压迫后,相应脊髓神经元胞体可见大量阳性深染区,主要集中在腹角及背角。Tunel染色示大鼠马尾神经压迫术后,在相应脊髓节段发现神经元凋亡,以脊髓前背角明显,与对照组相比,P<0.05;而各组DRG及马尾神经凋亡细胞少见,与对照组比较,P>0.05。术前DRG、马尾神经与脊髓中PUMA基因mRNA的表达水平,组间比较,P>0.05;术后相应脊髓中PUMA基因mRNA的表达水平随时间出现动态变化,术后第3天出现显著的PUMA增量调节,结果与术前相比,P<0.05;DRG、马尾神经中PUMA基因mRNA的表达水平变化与术前相比无明显变化,P>0.05。
结论:大鼠马尾神经压迫术后,可导致逆行性脊髓、背根节及马尾神经出现神经元凋亡。马尾神经受压后可在相应脊髓部位出现显著的PUMA增量调节。
第三部分:PUMA信号通路在马尾神经压迫损害致逆行性脊髓损害的作用
目的:在蛋白水平检测大鼠马尾神经压迫逆行性导致相应脊髓神经元凋亡作用中的凋亡相关蛋白的表达,探讨PUMA这一凋亡通路中的重要因子在马尾神经压迫中的作用,以及PUMA、p53、SirT2间的相互作用机制。
方法:用免疫组织化学的方法检测DRG、马尾神经与脊髓中p53、SirT2的表达。具体方法同上一部分。用Western-Blot方法检测脊髓中PUMA、p53、SirT2的表达:取100mg组织加入0.2ml裂解液进行匀浆提取蛋白,将所有蛋白样品调至等浓度后,加入上样缓冲液进行电泳,经转膜、封闭和孵育一抗、二抗后鉴定。
结果:p53免疫组织化学染色结果示:正常对照组少见明显阳性深染区。当大鼠马尾神经压迫后,相应脊髓神经元胞体可见大量阳性深染区。SirT2免疫组织化学染色结果示:A组在脊髓前背角可见阳性深染区。马尾神经受压迫后,脊髓内神经元胞体阳性深染区减少,颜色减淡,术后各组间差别不明显。马尾神经及DRG压迫前后未发现明显阳性表达。Western blot结果示,马尾神经压迫损伤后第3天,在相应脊髓组织内检测到显著的PUMA增量调节,同时出现p53的高表达;SirT2在相应的时间点出现表达量减少。
结论:大鼠马尾神经压迫损伤可以导致逆行性脊髓神经元出现凋亡,PUMA是其中的关键基因。PUMA在马尾神经压迫病理损害中的作用机制可能是通过p53通路,从而促进细胞凋亡。SirT2可能的作用是负向调节p53,从而抑制PUMA的表达。
Introduction
Along with the progress of medical knowledge and the deepening understanding of disease extent, more and more attention of Cauda Equina Compression (CEC) is paid to by scholars. Cauda equina syndrome (CES), a rare neurological disorder, is a combination of signs and symptoms resulting from lesion of the nerves in the CE. Typical manifestations can be associated variably with the disorders characterized by low back pain, unilateral or usually bilateral sciatica, bilateral weakness of the lower extremities, saddle or perianal hypoesthesia or anesthesia, sexual impotence, together with rectal and bladder sphincter dysfunction. The incidence of CES is variable, depending on the etiology of the syndrome. The prevalence among the general population has been estimated between 1:100,000 and 1:33,000. The most common cause of CES is herniation of a lumbar intervertebral disc. It is reported by approximately 1% to 10% of patients with herniated lumbar disks. The prevalence among patients with low back pain is approximately four in 10000. About nearly 30% of the lumbar spine disease in patients with different levels of existence CEC symptoms in our country. CEC has created the enormous pain for the patient, also gives the family and the society brings the serious burden. CEC researches are relatively few and slow now, and the prognosis seems poor. The mean reason for this is that the pathology physiology mechanism of CEC is very complex, and there is no comprehensive knowledge regarding it. Previous studies have shown that, the apoptosis of neuron caused by CEC is an important reason for the clinical symptoms. The domestic and foreign recent research suggests that it would forms the vicious circle after the CEC if the partial pathology change cannot have the prompt improvement. Local damage would cause extensive pathological damage, including anterograde damage, retrograde damage, transneuronal neuronal degeneration, and even transcellular central neuron degeneration. Thus the structure and function are hard to be repaired and lead to nonvolatile functional lesion. On this experimental basis, we plan to establish the animal model of CEC and do some preliminary study on this topic.
SECTION ONE:
Establishment and evaluation of the animal model of cauda equina compression and the nerve electrophysiological research
Objective: To do preliminary observation on lumbar region anatomy of the SD rat and relevant organization, and to establish the CEC animal models. To research on the neural physiological and behavioral, histologic and nerve electrophysiological changes based on this animal model.
Methods: We observed and measured the nomal anatomy of SD rats’lumbar region and relevant organization, and made certain the cross sectional area of lumbar spinal canal in SD rat. On the basis of above, we established a modified CEC animal model to analyze the effects of the pressure on the behavioral, histologic and nerve electrophysiological changes in rats. Eight-to-nine-week-old male SD rats were randomly divided into four groups: control group(CON),n=8; sham group(SHAM),n=8; classic cauda equina compression group (CCC),n=8; modified cauda equina compression group (MCC),n=9. The method to establish the modified CEC animal model: reveal the vertebral plate of L4 and L5, and excise the yellow ligament of L4/5. Insert a silicon rubber (10.0×1.0×1.1 mm to10.0×1.0×1.3 mm) to the caudal end. After induction of spinal stenosis walking function was measured using a treadmill apparatus and sensory functions were tested by measuring thermal and tactile withdrawal threshold (von Frey filaments) and BBB score for the period of 28 days after stenosis, which is day 1, 3, 7, 14, and 28. Using HE and Nissl's staining, we have taken a histopathology evaluation. Then, We measured the spinal cord evoked potential (SCEP) and motor nerve conduction velocity (MNCV) by using evoked potential recorder to investigate the nerve electrophysiological changes in CEC model.
Results: There is a low death rate in all experimental groups. The modified CEC animal model could mimic the situation of walking of human being which is neurological intermittent claudication. After the surgical compression, a significant running dysfunction, as evidenced by shortening of running distance, was measured as soon as 24 h after stenosis. This effect persisted for 28 days after surgery. There is no statistical difference between CCC and MCC. Similarly, a significant thermal and algaesthesia hyposensitivity was measured for a period of 28 days. BBB score decreased after the CEC, but recovered soon. There is no statistical difference between CCC and MCC in BBB score. HE and Nissl’s stain reveal that the number of medullated nerve fibers and tigroid body decrease, Wallerian's degeneration and demyelinate of neuron axon. SCEP increased significantly and couldn’t recover till 14 days after surgery; while MNCV recovered at the 7th day after surgery.
Conclusions: The modified CEC animal model could mimic the situation of walking of human being which is neurological intermittent claudication and is an easy and effective method to make CEC animal model. Behavior evaluation of this model suggests that sensory function and motor dysfunction could happen after CEC. Results of nerve electrophysiological experiment reveal that, the sensory brunch of CE is much more sensitive than locomotive brunch.
SECTION TWO:
Apoptosis of cellula nervosa and expression of PUMA in DRG, cauda equina and corresponding spinal cord after cauda equina compression
Objective: To learn if cauda equina compression could result in apoptosis in DRG, cauda equina and corresponding spinal cord after cauda equina compression, and to detect the expression of PUMA and find the change pattern with time.
Methods: Fifty eight-to-nine-week-old male SD rats were randomly divided into six groups: group A: control group (n=10); group B: one day after CEC (n=8); group C: three days after CEC (n=8); group D: seven days after CEC (n=8); group E: 14 days after CEC (n=8); group F: 28 days after CEC (n=8). The expressions of PUMA in DRG, cauda equina and corresponding spinal cord were detected by immunohistochemical methods described as follows: 10% formalin-fixed pancreatic tissue and paraffin-embedded pancreatic tissue were cut into sections with thickness of 4μm and placed onto glass-slides. Following deparaffinization in xylene, the slides were rehydrated and washed in Tris Buffered Saline (TBS). The endogenous peroxidase activity was quenched by 5 min incubation in a mixture of 3% hydrogen peroxide solution and 100% methanol. After being boiled in citrate buffer pH 6.0 for 20 mins, sections were sealed and left at room temperature for 20 min with 10% nonimmune goat serum in Tris-buffered saline solution (pH 7.5). After that, they were incubated with primary antibody at room temperature for 1 h, then with secondary antibody at room temperature for 30min. After washing with TBS, slides were kept in diaminobenzidine for 5-10 min and counterstained with Mayers hematoxylin.
The expressions of PUMA in DRG, cauda equina and corresponding spinal cord were detected by TdT-mediated X-dUTP nick end labeling (Tunel) methods described as follows: paraffin-embedded pancreatic tissue were cut into sections with thickness of 4μm and placed onto glass-slides. Following deparaffinization in xylene, the slides were rehydrated and washed in TBS. The endogenous peroxidase activity was quenched by 5 min incubation in a mixture of 3% hydrogen peroxide solution and protease K. After Tunel mixed liquor for one hour and Streptavidin-HRP for 30min. After washing with TBS, slides were kept in diaminobenzidine for 5-10 min and counterstained with Mayers hematoxylin.
Detect the mRNA expression level of PUMA in DRG, cauda equina and corresponding spinal cord by use Real Time PCR.
Results: Immunohistochemistry stain of p53 suggests that there are few positive cell in control group. Positive cell increased after the compression of CE could be found. We can find positive expression of Tunel in corresponding spinal cord tissue. The expression in spinal cord is significantly increased than control group (P<0.05). The expression of PUMA among DRG, cauda equina and corresponding spinal cord has no statistical difference (P>0.05). The expression of PUMA increased significantly on the third day after the compression (P<0.05), while there is no statistical difference of PUMA expression in DRG or CE after the surgery versus control group (P>0.05).
Conclusions: cauda equina compression could lead to retrogressional spinal cord lesion. The expression of PUMA increased significantly after the compression.
SECTION THREE: Preliminary study of the Basic Research on the nosogenesis of spinal cord after cauda equina compression
Objective: To detect the expression of apoptosis-associated protein in spinal cord after CEC in protein level; to approach the effect of PUMA in the process of apoptosis; to research the mechanism of interaction of PUMA, p53 and SirT2 in the pathogenesy of CEC.
Methods: Detect the expressions of PUMA in corresponding spinal cord by using immunohistochemical methods described in section one.
The expression of protein PUMA, p53 and SirT2 in spinal cord was detected by Western-Blot. Spinal cord tissue (100 mg) was homogenized in Lysis Buffer containing 50mM Tris·Cl (pH7.5), 150mM NaCl, 1% NP-40, 0.5% sodium desoxycholate (w/v), 0.1% SDS (w/v),10 mM mercaptoethanol,10mg/ml PMSF,5μg/ml Pepstatin,and 5μg/ml leupeptin (pH7.4). Electrophoresis of homogenated aliquots of protein was carried out using polyacrylamid gels. Separated proteins were then electrotransferred to the nitrocellulose membranes. These membranes were incubated in primary antibody for 24 h at 4°C and then in the secondary peroxidase-conjugated antibody for 2h. Immunoreactive protein bands were visualized using an enhanced chemiluminescence reaction kit.
Results: Immunohistochemistry stain of p53 suggests that there are few positive cells in control group. We can see that the positive cell increased after the compression of CE. Immunohistochemistry stain of SirT2 suggests that there are positive cell in control group. After the compression of CE, the anachromasis area decreased and lighted. The result of western blot suggests that at the day 3 after CEC, the expression of PUMA and p53 increased significantly and that of SirT2 decreased at the corresponding time.
Conclusions: Retrogressive apoptosis could happen after the compression of cauda equina. PUMA is the key gene in this course. The mechanism of action is depended the p53. p53 is involved in puma up-regulation and promote the apoptosis, while SirT2 may down-regulate the expression of PUMA.
随着医学的进步,人们对疾病认识程度的加深,马尾神经压迫损害(Cauda equina compression,CEC)及由此导致的马尾神经综合征(Cauda equina syndrome, CES)愈来愈引起学者们的重视。据统计,普通人群中CES的发病率为1:100,000到1:33,000之间,患有下腰痛的人群中CES发病率为万分之4,而在患有腰椎间盘突出的患者中,CES发病率更是达到了1%～10%。我国近30%的腰椎疾患的患者存在不同程度的CEC症状。马尾神经压迫损害及其继发性病理生理反应可直接导致组织器官神经功能损伤及功能障碍,导致下肢疼痛、运动感觉功能、大小便功能及性功能障碍,且其治疗困难,致残率非常高,给患者本人造成了极大的痛苦,也给家庭和社会带来沉重的负担。目前对CEC的研究相对较少而且缓慢,预后难以预料,主要是该病的病理生理机制非常复杂,对此认识还不够全面、深入。以往研究显示,马尾神经压迫损害致神经元的凋亡是造成马尾神经压迫临床症状的重要原因,但究竟是哪些基因参与了马尾神经压迫损害导致的神经元的凋亡尚不清楚。国内外近年研究显示,马尾神经压迫损伤后,其局部病理改变如不能得到及时改善,则形成恶性循环,由马尾神经的局部损害到广泛性病理损害,可产生顺行性、逆行性变性及传递性神经元变性,以至于产生跨细胞的中枢神经元变性,而致使其结构和功能难以修复,造成永久性的功能损害。在此实验基础上,本课题拟通过建立实验性大鼠马尾神经压迫模型,就马尾神经压迫损害的基础进行初步探讨。
第一部分:马尾神经压迫动物模型的建立及马尾神经压迫电生理的实验研究
目的:对SD大鼠腰椎区域相关组织解剖行初步观测,建立合适的马尾神经压迫损害动物模型,并在此基础上进行实验性大鼠急性马尾神经压迫后行为学、神经电生理及组织学研究。
方法:首先对SD大鼠腰椎区域相关组织解剖做了初步观测,得到SD大鼠腰椎区域相关解剖数据,根据测量数据制作改良的实验性大鼠急性马尾神经压迫动物模型。之后将实验动物随机分为以下4组:CON组:空白对照组(n=8);SHAM组:假手术组(n=8);CCC组:经典马尾神经压迫组(n=8);MCC组:改良马尾神经压迫组(n=9)。手术建立改良的实验性大鼠急性马尾神经压迫动物模型:显露L4～L5的椎板,扩大L4/5椎间隙,切除L4/5间隙的黄韧带,向尾端塞入10.0×1.0×(1.1-1.3)mm硅胶条1根。并与经典实验性大鼠急性马尾神经压迫动物模型进行比较。术后第1、3、7、14、28天对此模型进行了行为学评价,包括:BBB评分、电子von Frey机械测痛法测定大鼠缩足潜伏期、热板实验、甩尾实验、步行分析。结合HE染色及尼氏染色,光镜下对实验性大鼠急性马尾神经压迫模型进行组织病理学评价。在此基础上,使用诱发电位记录仪,进行了脊髓诱发电位(SCEP)N1波潜伏期及运动神经传导速度(MNCV)的动态测定,了解实验性大鼠急性马尾神经压迫后电生理的动态变化。
结果:模型制作大鼠死亡率低。步行分析强迫运动评价显示,模型组大鼠术后出现明显神经源性间歇性跛行,并且持续稳定,CON组与SHAM相比无明显差异;CCC组及MCC组相比无明显差异。BBB评分显示,与对照组相比,模型组术后静态运动功能减退不明显,非强迫运动功能术后恢复较早;相关感觉行为指标评价出现了明显感觉障碍,主要表现为痛觉及热觉减退,以术后早期明显,随着时间延长,感觉功能逐渐恢复,但未恢复到术前水平。通过对压迫DRG(DRG)、马尾神经(CE)及脊髓、圆锥的大体观、组织病理学的动态观察,可见神经根压迫后其有髓神经纤维数目减少和组织结构的改变,如神经膜细胞胞质肿胀和细胞水肿、尼氏体减少、华勒变性、神经元轴突脱髓鞘变等。电生理研究发现,马尾神经受压后SCEP发生的变化明显,潜伏期明显延长,至术后14天仍不能完全恢复;MNCV的下降恢复较快,术后7天即恢复到术前水平。
结论:本部分实验结果说明,改良的实验性大鼠急性马尾神经压迫模型可以复制出神经源性间歇性跛行,且更接近于椎管狭窄对马尾神经的压迫,为临床马尾神经压迫导致的疼痛及麻木治疗的研究建立了可供参考的动物模型。行为学评价说明,马尾神经压迫性损伤后,出现感觉功能障碍,且随着时间延长,神经功能有所恢复,但由于压迫因素未解除,神经功能不能恢复到术前水平。电生理实验研究说明马尾神经感觉支对机械压迫的反应比较敏感,而运动支相对则较容易恢复。
第二部分:马尾神经压迫后DRG、马尾神经与相应脊髓神经细胞凋亡及PUMA的表达
目的:研究马尾神经压迫后DRG、马尾神经与相应脊髓神经细胞有无凋亡的发生;了解马尾神经压迫后是否导致PUMA表达的变化以及表达数量随时间的变化,为手术时机的选择提供依据,以及为手术的疗效提供评价标准。
方法:将50只SD大鼠随机分为下列几组:A组:空白对照组(n=10);B组:马尾神经压迫1d组(n=8);C组:马尾神经压迫3d组(n=8);D组:马尾神经压迫7d组(n=8);E组:马尾神经压迫14d组(n=8);F组:马尾神经压迫28d组(n=8)。用免疫组织化学的方法检测DRG、马尾神经与相应脊髓中PUMA的表达。具体如下:4%的多聚甲醛灌注固定大鼠,取出标本,经石蜡包埋后切片,厚度在4μm。二甲苯脱蜡后,经梯度乙醇至水和TBS冲洗,用3%过氧化氢封闭内源性过氧化酶约5分钟,加入0.01M柠檬酸缓冲液(pH6.0),煮沸20分钟,再用5-10%山羊血清室温封闭20分钟。一抗孵育1h小时和二抗孵育30分钟后,用DAB显色处理,最后经TBS冲洗,苏木素复染和二甲苯透明后,用中性树胶封片。
用末端转移酶介导的dUTP缺口末端标记(Tunel)法检测DRG、马尾神经与相应脊髓中细胞凋亡:4μm石蜡切片常规脱蜡至水,3%过氧化氢封闭,蛋白酶K处理后置入Tunel混合液,37℃,1h,Streptavidin-HRP 30min后,0.04% DAB+0.03%H2O2显色10min,苏木素衬染和二甲苯透明后,常规树脂封片。
采用实时定量PCR技术检测DRG、马尾神经与相应脊髓中PUMA基因mRNA的表达水平:TRIzol法抽提细胞总RNA,RNA的鉴定及定量,逆转录至cDNA,引物设计与合成,BLAST确认引物特异性,测定各样品的Ct值,以β-actin浓度为参照对待测样品的Ct值进行校正。
结果:免疫组化结果示对照组未见明显PUMA阳性深染区。当大鼠马尾神经压迫后,相应脊髓神经元胞体可见大量阳性深染区,主要集中在腹角及背角。Tunel染色示大鼠马尾神经压迫术后,在相应脊髓节段发现神经元凋亡,以脊髓前背角明显,与对照组相比,P<0.05;而各组DRG及马尾神经凋亡细胞少见,与对照组比较,P>0.05。术前DRG、马尾神经与脊髓中PUMA基因mRNA的表达水平,组间比较,P>0.05;术后相应脊髓中PUMA基因mRNA的表达水平随时间出现动态变化,术后第3天出现显著的PUMA增量调节,结果与术前相比,P<0.05;DRG、马尾神经中PUMA基因mRNA的表达水平变化与术前相比无明显变化,P>0.05。
结论:大鼠马尾神经压迫术后,可导致逆行性脊髓、背根节及马尾神经出现神经元凋亡。马尾神经受压后可在相应脊髓部位出现显著的PUMA增量调节。
第三部分:PUMA信号通路在马尾神经压迫损害致逆行性脊髓损害的作用
目的:在蛋白水平检测大鼠马尾神经压迫逆行性导致相应脊髓神经元凋亡作用中的凋亡相关蛋白的表达,探讨PUMA这一凋亡通路中的重要因子在马尾神经压迫中的作用,以及PUMA、p53、SirT2间的相互作用机制。
方法:用免疫组织化学的方法检测DRG、马尾神经与脊髓中p53、SirT2的表达。具体方法同上一部分。用Western-Blot方法检测脊髓中PUMA、p53、SirT2的表达:取100mg组织加入0.2ml裂解液进行匀浆提取蛋白,将所有蛋白样品调至等浓度后,加入上样缓冲液进行电泳,经转膜、封闭和孵育一抗、二抗后鉴定。
结果:p53免疫组织化学染色结果示:正常对照组少见明显阳性深染区。当大鼠马尾神经压迫后,相应脊髓神经元胞体可见大量阳性深染区。SirT2免疫组织化学染色结果示:A组在脊髓前背角可见阳性深染区。马尾神经受压迫后,脊髓内神经元胞体阳性深染区减少,颜色减淡,术后各组间差别不明显。马尾神经及DRG压迫前后未发现明显阳性表达。Western blot结果示,马尾神经压迫损伤后第3天,在相应脊髓组织内检测到显著的PUMA增量调节,同时出现p53的高表达;SirT2在相应的时间点出现表达量减少。
结论:大鼠马尾神经压迫损伤可以导致逆行性脊髓神经元出现凋亡,PUMA是其中的关键基因。PUMA在马尾神经压迫病理损害中的作用机制可能是通过p53通路,从而促进细胞凋亡。SirT2可能的作用是负向调节p53,从而抑制PUMA的表达。
Introduction
Along with the progress of medical knowledge and the deepening understanding of disease extent, more and more attention of Cauda Equina Compression (CEC) is paid to by scholars. Cauda equina syndrome (CES), a rare neurological disorder, is a combination of signs and symptoms resulting from lesion of the nerves in the CE. Typical manifestations can be associated variably with the disorders characterized by low back pain, unilateral or usually bilateral sciatica, bilateral weakness of the lower extremities, saddle or perianal hypoesthesia or anesthesia, sexual impotence, together with rectal and bladder sphincter dysfunction. The incidence of CES is variable, depending on the etiology of the syndrome. The prevalence among the general population has been estimated between 1:100,000 and 1:33,000. The most common cause of CES is herniation of a lumbar intervertebral disc. It is reported by approximately 1% to 10% of patients with herniated lumbar disks. The prevalence among patients with low back pain is approximately four in 10000. About nearly 30% of the lumbar spine disease in patients with different levels of existence CEC symptoms in our country. CEC has created the enormous pain for the patient, also gives the family and the society brings the serious burden. CEC researches are relatively few and slow now, and the prognosis seems poor. The mean reason for this is that the pathology physiology mechanism of CEC is very complex, and there is no comprehensive knowledge regarding it. Previous studies have shown that, the apoptosis of neuron caused by CEC is an important reason for the clinical symptoms. The domestic and foreign recent research suggests that it would forms the vicious circle after the CEC if the partial pathology change cannot have the prompt improvement. Local damage would cause extensive pathological damage, including anterograde damage, retrograde damage, transneuronal neuronal degeneration, and even transcellular central neuron degeneration. Thus the structure and function are hard to be repaired and lead to nonvolatile functional lesion. On this experimental basis, we plan to establish the animal model of CEC and do some preliminary study on this topic.
SECTION ONE:
Establishment and evaluation of the animal model of cauda equina compression and the nerve electrophysiological research
Objective: To do preliminary observation on lumbar region anatomy of the SD rat and relevant organization, and to establish the CEC animal models. To research on the neural physiological and behavioral, histologic and nerve electrophysiological changes based on this animal model.
Methods: We observed and measured the nomal anatomy of SD rats’lumbar region and relevant organization, and made certain the cross sectional area of lumbar spinal canal in SD rat. On the basis of above, we established a modified CEC animal model to analyze the effects of the pressure on the behavioral, histologic and nerve electrophysiological changes in rats. Eight-to-nine-week-old male SD rats were randomly divided into four groups: control group(CON),n=8; sham group(SHAM),n=8; classic cauda equina compression group (CCC),n=8; modified cauda equina compression group (MCC),n=9. The method to establish the modified CEC animal model: reveal the vertebral plate of L4 and L5, and excise the yellow ligament of L4/5. Insert a silicon rubber (10.0×1.0×1.1 mm to10.0×1.0×1.3 mm) to the caudal end. After induction of spinal stenosis walking function was measured using a treadmill apparatus and sensory functions were tested by measuring thermal and tactile withdrawal threshold (von Frey filaments) and BBB score for the period of 28 days after stenosis, which is day 1, 3, 7, 14, and 28. Using HE and Nissl's staining, we have taken a histopathology evaluation. Then, We measured the spinal cord evoked potential (SCEP) and motor nerve conduction velocity (MNCV) by using evoked potential recorder to investigate the nerve electrophysiological changes in CEC model.
Results: There is a low death rate in all experimental groups. The modified CEC animal model could mimic the situation of walking of human being which is neurological intermittent claudication. After the surgical compression, a significant running dysfunction, as evidenced by shortening of running distance, was measured as soon as 24 h after stenosis. This effect persisted for 28 days after surgery. There is no statistical difference between CCC and MCC. Similarly, a significant thermal and algaesthesia hyposensitivity was measured for a period of 28 days. BBB score decreased after the CEC, but recovered soon. There is no statistical difference between CCC and MCC in BBB score. HE and Nissl’s stain reveal that the number of medullated nerve fibers and tigroid body decrease, Wallerian's degeneration and demyelinate of neuron axon. SCEP increased significantly and couldn’t recover till 14 days after surgery; while MNCV recovered at the 7th day after surgery.
Conclusions: The modified CEC animal model could mimic the situation of walking of human being which is neurological intermittent claudication and is an easy and effective method to make CEC animal model. Behavior evaluation of this model suggests that sensory function and motor dysfunction could happen after CEC. Results of nerve electrophysiological experiment reveal that, the sensory brunch of CE is much more sensitive than locomotive brunch.
SECTION TWO:
Apoptosis of cellula nervosa and expression of PUMA in DRG, cauda equina and corresponding spinal cord after cauda equina compression
Objective: To learn if cauda equina compression could result in apoptosis in DRG, cauda equina and corresponding spinal cord after cauda equina compression, and to detect the expression of PUMA and find the change pattern with time.
Methods: Fifty eight-to-nine-week-old male SD rats were randomly divided into six groups: group A: control group (n=10); group B: one day after CEC (n=8); group C: three days after CEC (n=8); group D: seven days after CEC (n=8); group E: 14 days after CEC (n=8); group F: 28 days after CEC (n=8). The expressions of PUMA in DRG, cauda equina and corresponding spinal cord were detected by immunohistochemical methods described as follows: 10% formalin-fixed pancreatic tissue and paraffin-embedded pancreatic tissue were cut into sections with thickness of 4μm and placed onto glass-slides. Following deparaffinization in xylene, the slides were rehydrated and washed in Tris Buffered Saline (TBS). The endogenous peroxidase activity was quenched by 5 min incubation in a mixture of 3% hydrogen peroxide solution and 100% methanol. After being boiled in citrate buffer pH 6.0 for 20 mins, sections were sealed and left at room temperature for 20 min with 10% nonimmune goat serum in Tris-buffered saline solution (pH 7.5). After that, they were incubated with primary antibody at room temperature for 1 h, then with secondary antibody at room temperature for 30min. After washing with TBS, slides were kept in diaminobenzidine for 5-10 min and counterstained with Mayers hematoxylin.
The expressions of PUMA in DRG, cauda equina and corresponding spinal cord were detected by TdT-mediated X-dUTP nick end labeling (Tunel) methods described as follows: paraffin-embedded pancreatic tissue were cut into sections with thickness of 4μm and placed onto glass-slides. Following deparaffinization in xylene, the slides were rehydrated and washed in TBS. The endogenous peroxidase activity was quenched by 5 min incubation in a mixture of 3% hydrogen peroxide solution and protease K. After Tunel mixed liquor for one hour and Streptavidin-HRP for 30min. After washing with TBS, slides were kept in diaminobenzidine for 5-10 min and counterstained with Mayers hematoxylin.
Detect the mRNA expression level of PUMA in DRG, cauda equina and corresponding spinal cord by use Real Time PCR.
Results: Immunohistochemistry stain of p53 suggests that there are few positive cell in control group. Positive cell increased after the compression of CE could be found. We can find positive expression of Tunel in corresponding spinal cord tissue. The expression in spinal cord is significantly increased than control group (P<0.05). The expression of PUMA among DRG, cauda equina and corresponding spinal cord has no statistical difference (P>0.05). The expression of PUMA increased significantly on the third day after the compression (P<0.05), while there is no statistical difference of PUMA expression in DRG or CE after the surgery versus control group (P>0.05).
Conclusions: cauda equina compression could lead to retrogressional spinal cord lesion. The expression of PUMA increased significantly after the compression.
SECTION THREE: Preliminary study of the Basic Research on the nosogenesis of spinal cord after cauda equina compression
Objective: To detect the expression of apoptosis-associated protein in spinal cord after CEC in protein level; to approach the effect of PUMA in the process of apoptosis; to research the mechanism of interaction of PUMA, p53 and SirT2 in the pathogenesy of CEC.
Methods: Detect the expressions of PUMA in corresponding spinal cord by using immunohistochemical methods described in section one.
The expression of protein PUMA, p53 and SirT2 in spinal cord was detected by Western-Blot. Spinal cord tissue (100 mg) was homogenized in Lysis Buffer containing 50mM Tris·Cl (pH7.5), 150mM NaCl, 1% NP-40, 0.5% sodium desoxycholate (w/v), 0.1% SDS (w/v),10 mM mercaptoethanol,10mg/ml PMSF,5μg/ml Pepstatin,and 5μg/ml leupeptin (pH7.4). Electrophoresis of homogenated aliquots of protein was carried out using polyacrylamid gels. Separated proteins were then electrotransferred to the nitrocellulose membranes. These membranes were incubated in primary antibody for 24 h at 4°C and then in the secondary peroxidase-conjugated antibody for 2h. Immunoreactive protein bands were visualized using an enhanced chemiluminescence reaction kit.
Results: Immunohistochemistry stain of p53 suggests that there are few positive cells in control group. We can see that the positive cell increased after the compression of CE. Immunohistochemistry stain of SirT2 suggests that there are positive cell in control group. After the compression of CE, the anachromasis area decreased and lighted. The result of western blot suggests that at the day 3 after CEC, the expression of PUMA and p53 increased significantly and that of SirT2 decreased at the corresponding time.
Conclusions: Retrogressive apoptosis could happen after the compression of cauda equina. PUMA is the key gene in this course. The mechanism of action is depended the p53. p53 is involved in puma up-regulation and promote the apoptosis, while SirT2 may down-regulate the expression of PUMA.
引文
1. Scott PJ. Bladder paralysis in cauda equina lesions from disc prolapse. J Bone Joint Surg Br 1965; 47: 224-235. PMID: 14302723
2. Floman Y, Wiesel SW, Rothman RH. Cauda equina syndrome presenting as a herniated lumbar disk. Clin Orthop Relat Res 1980; 147: 234-237. PMID: 7371304
3. Byrne TN. Disorders of the spinal cord and cauda equina. Curr Opin Neurol Neurosurg 1993; 6: 545-548. PMID: 8400466
4. Shapiro S. Cauda equina syndrome secondary to lumbar disc herniation. Neurosurg 1993; 32: 743-747. PMID: 8492849
5. Kostuik JP, Harrington I, Alexander D, Rand W, Evans D. Cauda equina syndrome and lumbar disc herniation. J Bone Joint Surg Am 1986; 68: 386-391. PMID: 2936744
6. Lazarius A. Historia anatomica humani corporis. 1600, Becker: Frankfurt, Germany. 178.
7. Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 1934; 211: 210-215.
8. Mooney V. Differential diagnosis of low back disorders: principles of classification. In: Frymore JW, eds. The adult spine. New York: Raven Press; 1991: 1559-1560.
9. Shapiro S. Medical realities of cauda equina syndrome secondary to lumbar disc herniation. Spine 2000; 25: 348-352. PMID: 10703108
10. Gleave JR, Macfarlane R. Cauda equina syndrome: what is the relationship between timing of surgery and outcome? Br J Neurosurg 2002; 16: 325-328. PMID: 12389883
11. Gleave JR, MacFarlane R. Prognosis for recovery of bladder function following lumbar central disc prolapse. Br J Neurosurg 1990; 4: 205-209. PMID: 2397046
12. Raaf J. Removal of protruded lumbar intervertebral discs. J Neurosurg 1970; 32: 604-611. PMID: 5438104
13. Chang HS, Nakagawa H, Mizuno J. Lumbar herniated disc presenting with cauda equina syndrome. Long-term follow-up of four cases. Surg Neurol 2000; 53: 100-104. PMID: 10713185
14. O’Connell JE. Protrusions of the lumbar intervertebral discs: a clinical review based on five hundred cases treated by excision of the protrusion. J Bone Joint Surg Br 1951; 33: 8-30. PMID: 14814156
15. Kostuik JP. Medicolegal consequences of cauda equina syndrome: an overview. Neurosurg Focus 2004; 16: 39-41. PMID: 15202878
16. Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain. JAMA 1992; 268: 760-765. PMID: 1386391
17. Parke WW, Gammell K, Rothman RH. Arterial vascularization of the cauda equina. J Bone Joint Surg Am 1981; 63: 53-62. PMID: 7005240
18. Kou J, Fischgrund J, Biddinger A, Herkowitz H. Risk factors for spinal epidural hematoma after spinal surgery. Spine 2002; 27: 1670-1673. PMID: 12163731
19. Groen RJ, Ponssen H. The spontaneous spinal epidural hematoma. A study of the etiology. J Neurol Sci 1990; 98: 121-138. PMID: 2243224
20. Della-Giustina. Emergency department evaluation and treatment of back pain. Emerg Med Clin North Am 1999; 17: 877-893. PMID: 10584107
21. Kennedy JG, Soffe KE, McGrath A, Stephens MM, Walsh MG, McManus F. Predictors of outcome in cauda equina syndrome. Eur Spine J 1999; 8: 317-322. PMID: 10483835
22. Tay EC, Chacha PB. Midline prolapse of a lumbar intervertebral disc with compression of the cauda equina. J Bone Joint Surg Br 1979; 61: 43-46. PMID: 154521
23. Saint-Louis LA. Lumbar spinal stenosis assessment with computed tomography, magnetic resonance imaging, and myelography. Clin Orthop Relat Res 2001; 384: 122-136. PMID: 11249157
24. Bischoff RJ, Rodriguez RP, Gupta K, Righi A, Dalton JE, Whitecloud TS. A comparison of computed tomography-myelography, magnetic resonance imaging, and myelography in the diagnosis of herniated nucleus pulposus and spinal stenosis. J Spinal Disord 1993; 6: 289-295. PMID: 8219542
25. Modic MT, Masaryk T, Boumphrey F, Goormastic M, Bell G. Lumbar herniated disk disease and canal stenosis: prospective evaluation by surface coil MR, CT, and myelography. Am J Roentgenol 1986; 147: 757-765. PMID: 3489378
26. Kent DL, Haynor DR, Larson EB, Deyo RA. Diagnosis of lumbar spinal stenosis in adults: a metaanalysis of the accuracy of CT, MR, and myelography. Am J Roentgenol 1992; 158: 1135-1144. PMID: 1533084
27. Bundschuh CV, Modic MT, Ross JS, Masaryk TJ, Bohlman H. Epidural fibrosis and recurrent disk herniation in the lumbar spine: MR imaging assessment. Am J Roentgenol 1988; 150: 923-932. PMID: 3258108
28. Bell DA, Collie D, Statham PF. Cauda equina syndrome: what is the correlation between clinical assessment and MRI scanning? Br J Neurosurg 2007; 21: 201-203. PMID: 17453789
29. Tandon PN, Sankaren B. Cauda equina syndrome due to lumbar disc prolapse. Indian J Orthop 1967; 1: 112-116.
30. Shephard RH. Diagnosis and prognosis of cauda equina syndrome produced by protrusion oflumbar disk. Br Med J 1959; 2: 1434-1439. PMID: 14445833
31. Shi JG, Jia LS, Yuan W, Ye XJ, Chen DY, Ni B, et al. Clinical stages and early diagnosis of cauda equina syndrome due to lumbo-sacral nerve injury. Orthop J Chin (Chin) 2005; 7: 491-493.
32. Jaradeh S. Cauda equina syndrome: a neurologist's perspective. Reg Anesth 1993; 18(6 Suppl): 473-480. PMID: 8110650
33. OrendácováJ, CízkováD, Kafka J, LukácováN, Marsala M, Sulla I, et al. Cauda equina syndrome. Prog Neurobiol 2001; 64: 613-637. PMID: 11311464
34. Nakai K, Takenobu Y, Takimizu H, Akimaru S, Maegawa H, Ito H, et al. Effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model: comparison with nifedipine, ticlopidine and cilostazol. Prostaglandins Other Lipid Mediat 2003; 71: 253-263. PMID: 14518565
35. Murakami M, Takahashi K, Sekikawa T, Yasuhara K, Yamagata M, Moriya H. Effects of intravenous lipoprostaglandin E1 on neurogenic intermittent claudication. J Spinal Disord 1997; 10: 499-504. PMID: 9438815
36. Konno S, Kayama S, Olmarker K, Kikuchi S. Effects of OP-1206 (prostaglandin E1) on nerve-conduction velocity in the dog cauda equina subjected to acute experimental compression. J Spinal Disord 1996; 9: 103-106. PMID: 8793775
37. Yamamoto T, Shimoyama N, Asano H, Mizuguchi T. OP-1206, a prostaglandin E1 derivative, attenuates the thermal hyperesthesia induced by constriction injury to the sciatic nerve in the rat. Anesth Analg 1995; 80: 515-520. PMID: 7864417
38. Yone K, Sakou T, Kawauchi Y. The effect of Lipoprostaglandin E1 on cauda equina blood flow in patients with lumbar spinal canal stenosis: myeloscopic observation. Spinal Cord 1999; 37: 269-274. PMID: 10338347
39. Nakai K, Takenobu Y, Eguchi K, Takimizu H, Honjo K, Akimaru S, et al. The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model. Anesth Analg 2002; 94: 1537-1541. PMID: 12032022
40. Nakai K, Takenobu Y, Takimizu H, Akimaru S, Ito H, Maegawa H, et al. Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model. Prostaglandins Leukot Essent Fatty Acids 2003; 69: 269-273. PMID: 12907137
41. Koes BW, Scholten RJ, Mens JM, Bouter LM. Efficacy of non-steroidal anti-inflammatory drugs for low back pain: a systematic review of randomised clinical trials. Ann Rheum Dis 1997; 56: 214-223. PMID: 9165992
42. Pohjolainen T, Jekunen A, Autio L, Vuorela H. Treatment of acute low back pain with the COX-2-selective anti-inflammatory drug nimesulide: Results of a randomized, double-blind comparative trial versus ibuprofen. Spine 2000; 25: 1579-1585. PMID: 10851109
43. van Tulder MW, Scholten RJ, Koes BW, Deyo RA. Nonsteroidal anti-inflammatory drugs for low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group. Spine 2000; 25: 2501-2513. PMID: 11013503
44. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain: an updated cochrane review. Spine 2008; 33: 1766-1774. PMID: 18580547
45. Abram SE, O'Connor TC. Complications associated with epidural steroid injections. Reg Anesth 1996; 21: 149-162. PMID: 8829408
46. Fukusaki M, Kobayashi I, Hara T, Sumikawa K. Symptoms of spinal stenosis do not improve after epidural steroid injection. Clin J Pain 1998; 14: 148-151. PMID: 9647457
47. Hirata F, Schiffmann E, Venkatasubramanian K, Salomon D, Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci USA 1980; 77: 2533-2536. PMID: 6930649
48. Tsurufuji S, Sugio K, Takemasa F. The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone. Nature 1979; 280: 408-410. PMID: 460415
49. Vane J, Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs. FASEB J 1987; 1: 89-96. PMID: 3111928
50. Ardoin SP, Sundy JS. Update on nonsteriodal anti-inflammatory drugs. Curr Opin Rheumatol 2006; 18: 221-226. PMID: 16582683
51. Nakano M, Matsui H, Miaki K, Tsuji H. Postlaminectomy adhesion of the cauda equina: inhibitory effects of anti-inflammatory drugs on cauda equina adhesion in rats. Spine 1998;23: 298-304. PMID: 9507616
52. MacKay MA, Fischgrund JS, Herkowitz HN, Kurz LT, Hecht B, Schwartz M. The effect of interposition membrane on the outcome of lumbar laminectomy and discectomy. Spine 1995; 20: 1793-1796. MID: 7502136
53. Einhaus SL, Robertson JT, Dohan FC Jr, Wujek JR, Ahmad S. Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L). Spine 1997; 22: 1440-1447. PMID: 9231961
54. Sandoval MA, Hernandez-Vaquero D. Preventing peridural fibrosis with nonsteroidal anti-inflammatory drugs. Eur Spine J 2008; 17: 451-455. PMID: 18172695
55. Jacobs RR, McClain O, Neff J. Control of postlaminectomy scar formation: an experimental and clinical study. Spine 1980; 5: 223-229. PMID: 7394661
56. Bartels RH, de Vries J. Hemi-cauda equina syndrome from herniated lumbar disc: a neurosurgical emergency? Can J Neurol Sci 1996: 23; 296-299. PMID: 8951209
57. Jones DL, Moore T. The types of neuropathic bladder dysfunction associated with prolapsed lumbar intervertebral discs. Br J Urol 1973; 45: 39-43. PMID: 4690149
58. Nielsen B, de Nully M, Schmidt K, Hansen RI. A urodynamic study of cauda equina syndrome due to lumbar disc herniation. Urol Int 1980; 35: 167-170. PMID: 7385464
59. DeLong WB, Polissar N, Neradilek B. Timing of surgery in cauda equina syndrome with urinary retention: meta-analysis of observational studies. J Neurosurg Spine 2008; 8: 305-320. PMID: 18377315
60. Mangialardi R, Mastorillo G, Minoia L, Garofalo R, Conserva F, Solarino GB. Lumbar disc herniation and cauda equina syndrome. Considerations on a pathology with different clinical manifestations. Chir Organi Mov 2002; 87: 35-42. PMID: 12198948
61. McLaren AC, Bailey SI. Cauda equina syndrome: a complication of lumbar discectomy. Clin Orthop Relat Res 1986; 204: 143-149. PMID: 3956005
62. Hellstr?m P, Kortelainen P, Kontturi M. Late urodynamic findings after surgery for cauda equina syndrome caused by a prolapsed lumbar intervertebral disk. J Urol 1986; 135: 308-312. PMID: 3944866
63. Ahn UM, Ahn NU, Buchowski JM, Garrett ES, Sieber AN, Kostuik JP. Cauda equina syndrome secondary to lumbar disc herniation: a meta-analysis of surgical outcomes. Spine 2000; 25: 1515-1522. PMID: 10851100
64. Thongtrangan I, Le H, Park J, Kim DH. Cauda equina syndrome in patients with low lumbar fractures. Neurosurg Focus 2004; 16: e6. PMID: 15202876
65. Kohles SS, Kohles DA, Karp AP, Erlich VM, Polissar NL. Time-dependent surgical outcomes following cauda equina syndrome diagnosis: comments on a meta-analysis. Spine 2004; 29: 1281-1287. PMID: 15167669
66. Hussain SA, Gullan RW, Chitnavis BP. Cauda equina syndrome: outcome and implications for management. Br J Neurosurg 2003; 17: 164-167. PMID: 12820760
67. Qureshi A, Sell P. Cauda equina syndrome treated by surgical decompression: the influence of timing on surgical outcome. Eur Spine J 2007; 16: 2143-2151. PMID: 17828560
68. Buchner M, Schiltenwolf M. Cauda equina syndrome caused by intervertebral lumbar disk prolapse: mid-term results of 22 patients and literature review. Orthopedics 2002; 25: 727-731.PMID: 12138958
69. Borovich B, Zaaroor M, Gruszkiewicz J. The syndrome of the central L-3-herniated disc with special emphasis on motor involvement. Acta Neurochir (Wien) 1984; 70: 115-125. PMID: 6741627
70. McCarthy MJ, Aylott CE, Grevitt MP, Hegarty J. Cauda equina syndrome: factors affecting long-term functional and sphincteric outcome. Spine 2007; 32: 207-216. PMID: 17224816
71. Jensen RL. Cauda equina syndrome as a postoperative complication of lumbar spine surgery. Neurosurg Focus. 2004; 16: e7. PMID: 15202877
72. Foo D, Rossier AB. Preoperative neurological status in predicting surgical outcome of spinal epidural hematomas. Surg Neurol 1981; 15: 389-401. PMID: 9760981
73. Deyo RA, Cherkin DC, Loeser JD, Biqos SJ, Ciol MA. Morbidity and mortality in association with operations on the lumbar spine. The influence of age, diagnosis, and procedure. J Bone Joint Surg Am 1992; 74: 536-543. PMID: 1583048
74. Bohlman HH, Kirkpatrick JS, Delamarter RB, Leventhal M. Anterior decompression for late pain and paralysis after fractures of the thoracolumbar spine. Clin Orthop Relat Res 1994; 300: 24-29. PMID: 8131342
75. Schaeffer HR. Cauda equina compression resulting from massive lumbar disc extrusion. Aust N Z J Surg 1966; 35: 300-306. PMID: 5220085
76. Ramirez LF, Thisted R. Complications and demographic characteristics of patients undergoing lumbar discectomy in community hospitals. Neurosurgery 1989; 25: 226-231. PMID: 2770987
77. Lenehan B, Sullivan P, Street J, Dudeney S. Epidural abscess causing cauda equina syndrome. Ir J Med Sci 2005; 174: 88-91. PMID: 16285347
78. Reihsaus E, Waldbaur H, Seeling W. Spinal epidural abscess: a meta-analysis of 915 patients. Neurosurg Rev 2000; 23: 175-205. PMID: 11153548
79. Rigamonti D, Liem L, Sampath P, Knoller N, Namaguchi Y, Schreibman DL, et al. Spinal epidural abscess: contemporary trends in etiology, evaluation, and management. Surg Neurol 1999; 52: 189-197. PMID: 10447289
80. Tang HJ, Lin HJ, Liu YC, Li CM. Spinal epidural abscess-experience with 46 patients and evaluation of prognostic factors. J Infect 2002; 45: 76-81. PMID: 12217707
81. Yilmaz C, Selek HY, Gürkan I, Erdemli B, Korkusuz Z. Anterior instrumentation for the treatment of spinal tuberculosis. J Bone Joint Surg Am 1999; 81: 1261-1267. PMID: 10505522
82. Govender S, Parbhoo AH. Support for the anterior column with allografts in tuberculosis of the spine. J Bone Joint Surg Br 1998; 81: 106-109. PMID: 10068015
83. Cohen DB. Infectious origins of cauda equina syndrome. Neurosurg Focus 2004; 16: e2. PMID: 15202872
84. Faraj A, Krishna M, Mehdian SM. Cauda equina syndrome secondary to lumbar spondylodiscitis caused by streptococcus milleri. Eur Spine J 1996; 5: 134-136. PMID: 8724196
85. Brecker SJ, Pugey CD. Nocardia asteroides infection of the cauda equina. J Neurol Neurosurg Psychiatry 1988; 51: 309-311. PMID: 3346704
86. Kapoor SK, Garg V, Dhaon BK, Jindal M. Tuberculosis of the posterior vertebral elements: a rare cause of compression of the cauda equina. A case report. J Bone Joint Surg Am 2005; 87: 391-394. PMID: 15687164
87. Carod-Artal FJ. Neurological complications of Schistosoma infection. Trans R Soc Trop Med Hyg 2008; 102: 107-16. PMID: 17905371
88. Chen HJ, Liang CL, Lu K, Liliang PC, Tsai YD. Cauda equina syndrome caused by delayed traumatic spinal subdural haematoma. Injury 2001; 32: 505-507. PMID: 11476820
89. Harrop JS, Hunt GE Jr, Vaccaro AR. Conus medullaris and cauda equina syndrome as a result of traumatic injuries: management principles. Neurosurg Focus 2004; 16: e4. PMID: 15202874
90. Schoenecker PL, Cole HO, Herring JA, Capelli AM, Bradford DS. Cauda equina syndrome after in situ arthrodesis for severe spondylolisthesis at the lumbosacral junction. J Bone Joint Surg Am 1990; 72: 369-377. PMID: 2312532
91. Cheung EV, Herman MJ, Cavalier R, Pizzutillo PD. Spondylolysis and spondylolisthesis in children and adolescents: II. Surgical management. J Am Acad Orthop Surg 2006; 14(8): 488-498. PMID: 16885480
92. Shaw M, Birch N. Facet joint cysts causing cauda equina compression. J Spinal Disord Tech 2004; 17: 442-445. PMID: 15385886
93. Ahn NU, Ahn UM, Nallamshetty L, Springer BD, Buchowski JM, Funches L, et al. Cauda equina syndrome in ankylosing spondylitis (the CES-AS syndrome): meta-analysis of outcomes after medical and surgical treatments. J Spinal Disord 2001; 14: 427-433. PMID: 11586143
94. Tullous MW, Skerhut HE, Story JL, Brown WE Jr, Eidelberg E, Dadsetan MR, et al. Cauda equina syndrome of long-standing ankylosing spondylitis. Case report and review of the literature. J Neurosurg 1990; 73: 441-447. PMID: 2200856
95. Johnsson KE, Sass M. Cauda equina syndrome in lumbar spinal stenosis: case report and incidence in Jutland, Denmark. J Spinal Disord Tech. 2004 Aug; 17: 334-5. PMID: 15280766
96. Schatzker J, Pennal GF. Spinal stenosis, a cause of cauda equina compression. J Bone Joint Surg Br 1968; 50: 606-618. PMID: 4235812
97. Storm PB, Chou D, Tamargo RJ. Lumbar spinal stenosis, cauda equina syndrome, and multiple lumbosacral radiculopathies. Phys Med Rehabil Clin N Am 2002; 13: 713-733. PMID: 12380555
98. Rubenstein DJ, Ghelman B. Case report 477: Cauda equina syndrome (CES) complicating long-standing ankylosing spondylitis (AS). Skeletal Radiol 1988; 17: 212-215. PMID: 3375851
99. Baba H, Maezawa Y, Furusawa N, Imura S, Tomita K. The role of calcium deposition in the ligamentum flavum causing a cauda equina syndrome and lumbar radiculopathy. Paraplegia 1995; 33: 219-223. PMID: 7609980
100. Jauslin PA, Müller AF, Myers P, Velebit V. Cauda equina syndrome associated with an aorto-caval fistula. Eur J Vasc Surg 1991; 5: 471-473. PMID: 1915914
101. Henriques T, Olerud C, Petrén-Mallmin M, Ahl T. Cauda equina syndrome as a postoperative complication in five patients operated for lumbar disc herniation. Spine 2001; 26: 293-297. PMID: 11224866
102. Dimopoulos V, Fountas KN, Machinis TG, Feltes C, Chung I, Johnston K, et al. Postoperative cauda equina syndrome in patients undergoing single-level lumbar microdiscectomy. Report of two cases. Neurosurg Focus 2005; 19: e11. PMID: 16122210
103. Str?mqvist B, J?nsson B, Annertz M, Holt?s S. Cauda equina syndrome caused by migrating fat graft after lumbar spinal decompression. A case report demonstrated with magnetic resonance imaging. Spine 1991; 16: 100-101. PMID: 2003232
104. Prusick VR, Lint DS, Bruder WJ. Cauda equina syndrome as a complication of free epidural fat-grafting. A report of two cases and a review of the literature. J Bone Joint Surg Am. 1988 Sep; 70: 1256-1258. PMID: 3417714
105. Mayer PJ, Jacobsen FS. Cauda equina syndrome after surgical treatment of lumbar spinal stenosis with application of free autogenous fat graft. A report of two cases. J Bone Joint Surg Am. 1989; 71: 1090-1093. PMID: 2760085
106. Onik G, Maroon JC, Jackson R. Cauda equina syndrome secondary to an improperly placed nucleotome probe. Neurosurgery 1992; 30: 412-415. PMID: 1620307
107. Dickman CA, Shedd SA, Spetzler RF, Shetter AG, Sonntag VK. Spinal epidural hematoma associated with epidural anesthesia: complications of systemic heparinization in patients receiving peripheral vascular thrombolytic therapy. Anesthesiology 1990; 72: 947-950. PMID: 2339809
108. Liu YC, Wu RS, Wong CS. Unexpected complication of attempted epidural anaesthesia: cauda equina syndrome. Anaesth Intensive Care 2003; 31: 461-464. PMID: 12973972
109. Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, et al. Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 1991; 72: 275-281. PMID: 1994754
110. Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier F, et al. Complications of regional anesthesia in France: the SOS regional anesthesia hotline service. Anesthesiology 2002; 97: 1274-1280. PMID: 12411815
111. Oppenheim JS, Spitzer DE, Segal DH. Nonvascular complications following spinal manipulation. Spine J 2005; 5: 660-667. PMID: 16291108
112. Marhouitz HD, Dloce DT. Cauda equina syndrome due to sequestrated recurrent disk herniation after chiropractic manipulation. Orthopedics 1997; 20: 652-653. PMID: 9243679
113. Haldeman S, Rubinstein SM. Cauda equina syndrome in patients undergoing manipulation of the lumbar spine. Spine 1992; 17: 1469-1473. PMID: 1471004
114. Simou N, Zioga A, Zygouris A, Pahatouridis D, Charalabopoulos K, Batistatou A. Plexiform neurofibroma of the cauda equina: a case report and review of the literature. Int J Surg Pathol 2008; 16: 78-80. PMID: 18203792
115. Gaetani P, Di Ieva A, Colombo P, Tancioni F, Aimar E, Debernardi A, et al. Intradural spinal metastasis of renal clear cell carcinoma causing cauda equina syndrome. Acta Neurochir (Wien) 2004; 146: 857-861. PMID: 15254809
116. Lampl Y, Eshel Y, Gilad R, Sarova-Pinchas I. Glioblastoma multiforme with bone metastase and cauda equina syndrome. J Neurooncol 1990; 8: 167-172. PMID: 2162916
117. Bagley CA, Gokaslan ZL. Cauda equina syndrome caused by primary and metastatic neoplasms. Neurosurg Focus 2004; 16: e3. PMID: 15202873
118. Kotil K, Kilinc BM, Bilge T. Spinal metastasis of occult lung carcinoma causing cauda equina syndrome. J Clin Neurosci 2007; 14: 372-375. PMID: 17336230
119. Poncelet A. The neurologic complications of Paget's disease. J Bone Miner Res 1999; 14(Suppl 2): 88-91. PMID: 10510221
120. Richter RL, Semble EL, Turner RA, Challa VR. An unusual manifestation of Paget's disease of bone: spinal epidural hematoma presenting as acute cauda equina syndrome. J Rheumatol 1990; 17: 975-978. PMID: 2213767
121. Frenay J, Lambooy N. Cauda equina syndrome following spondylolisthesis by low lumbar involvement of chronic rheumatoid arthritis. Neurochirurgie 1974; 20: 431-440. PMID: 4468381
122. Kawaji H, Miyamoto M, Gembun Y, Ito H. A case report of rapidly progressing cauda equina symptoms due to rheumatoid arthritis. J Nippon Med Sch 2005; 72: 290-294. PMID: 16247229
123. Sant SM, O'Connell D. Cauda equina syndrome in ankylosing spondylitis: a case report and review of the literature. Clin Rheumatol 1995; 14: 224-226. PMID: 7789067
124. Schr?der R, Urbach H, Zierz S. Cauda equina syndrome with multiple lumbar diverticulacomplicating long-standing ankylosing spondylitis. Clin Investig 1994; 72: 1056-1059. PMID: 7711415
125. Groen RJ, Ponssen H. The spontaneous spinal epidural hematoma: a study of the etiology. J Neurol Sci 1990; 98: 121-138. PMID: 2243224
126. Mohit AA, Fisher DJ, Matthews DC, Hoffer E, Avellino AM. Inferior vena cava thrombosis causing acute cauda equina syndrome. Case report. J Neurosurg 2006; 104(1 Suppl): 46-49. PMID: 16509481
127. Domenicucci M, Ramieri A, Ciappetta P, Delfini R. Nontraumatic acute spinal subdural hematoma: report of five cases and review of the literature. J Neurosurg 1999; 91(1 Suppl): 65-73. PMID: 10419371
128. Morandi X, Riffaud L, Chabert E, Brassier G. Acute nontraumatic spinal subdural hematomas in three patients. Spine 2001; 26: E547-551. PMID: 11725255
129. Russell NA, Benoit BG. Spinal subdural hematoma. A review. Surg Neurol 1983; 20: 133-137. PMID: 6879409
1贾连顺主编.现代脊柱外科学.北京.人民军医出版社. 2007; 865-875.
2 Mooney V. Differential Diagnosis of Low Back Disorders. Principles of classification. In: J. W. Frymore, editor in chief. Raven Press, Lt. d, New York. The Adult Spine. 1991; 1559-60.
3 Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain. JAMA 1992; 268(6):760-765.
4 Kostuik JP, Harrington I, Alexander D, Rand W, Evans D. Cauda equina syndrome and lumbar disc herniation. J Bone Joint Surg Am, 1986; 68: 386-391.
5 Shapiro S. Cauda equina syndrome secondary to lumbar disc herniation. Neurosurg 1993; 32(3): 743-747.
6 Shapiro S. Medical realities of cauda equina syndrome secondary to lumbar disc herniation. Spine. 2000; 25(3):348-51; discussion 352.
7 Gleave JR, Macfarlane R. Cauda equina syndrome: what is the relationship between timing of surgery and outcome? Br J Neurosurg 2002; 16(4):325-328.
8 Gleave JR, MacFarlane R. Prognosis for recovery of bladder function following lumbar central disc prolapse. Br J Neurosurg 1990; 4(3):205-209.
9 Raaf J. Removal of protruded lumbar intervertebral discs. J Neurosurg 1970; 32(5):604-611.
10 Chang HS, Nakagawa H, Mizuno J. Lumbar herniated disc presenting with cauda equina syndrome. Long-term followup of four cases. Surg Neurol 2000; 53(2):100-104.
11 O’Connell JE. Protrusions of the lumbar intervertebral discs: a clinical review based on five hundred cases treated by excision of the protrusion. J Bone Joint Surg Br 1951; 33:8-30.
12 Kostuik JP. Medicolegal consequences of cauda equina syndrome: an overview. Neurosurg Focus 2004; 16:39-41.
13史建刚,贾连顺,李家顺,蔡凯华,刘颜玲,倪灿荣,贾宁阳.第二军医大学学报. 2003; 24(01):83-86.
14史建刚,贾连顺,苟三怀,肖建如,叶晓健,谭军,陈雄生,贾宁阳。神经根损害神经根后根节病理变化的实验研究。中国矫形外科杂志, 2002; 10(13): 1317-1318.
15王金武,侯春林,陈爱民,王诗波,赵良宇. SD大鼠马尾与骶神经根的解剖学观察.中国临床解剖学杂志, 2003; 21(4): 368-370.
16 Anatomy of the Laboratory Rat. R. Hebel and M. W. Stromberg. Published by Burns &McEachern, Don Mills, Ontario. 1976.
17 Yagi J, Sμmino R. Inhibition of a hyperpolarization-activated current by clonidine in rat dorsal rootganglion neurons. J Neurophysiol. 1998; 80(3): 1094-104.
18 Olmarker K. Spinal nerve root compression. Nutrition and function of the porcine cauda equina compressed in vivo. Acta Orthop Scand Suppl. 1991; 242: 1-27.
19 Olmarker K, Holm S, Rosenqvist AL, Rydevik B. Experimental nerve root compression. A model of acute, graded compression of the porcine cauda equina and an analysis of neural and vascular anatomy. Spine. 1991 Jan; 16(1): 61-9.
20 Inman DM, Steward O. Physical size does not determine the unique hIst0path0l0gical response seen in the injured mouse spinal cord. J Neurotraμma, 2003, 20(1): 33-42.
21 Hedrich HJ: History, strains and models. In: Krinke GJ eds. The laboratory rat. London & San Diego: Academic Press, 2000: 3-16.
22 Metz GA, Curt A, van de Meent H. et a1. Validation of the weightdrop contusion model in rats: a comparative study of human spinal cord injury. J Neurotraμma, 2000, 17(1): 1-17.
23 Rauschning W, Bergstr?m K, Pech P. Correlative craniospinal anatomy studies by computed tomography and cryomicrotomy. J Comput Assist Tomogr. 1983 Feb; 7(1): 9-13. PMID: 6826854
24 Parke WW, Gammell K, Rothman RH. Arterial vascularization of the cauda equina. J Bone Joint Surg Am. 1981 Jan; 63(1): 53-62. PMID: 7005240
25 Parke WW. Intrinsic vasculature of the lumbosacral spinal nerve roots. Orthopedics. 1991 Apr; 14(4): 455-7.
26 OrendácováJ, CízkováD, Kafka J, LukácováN, Marsala M, Sulla I, et al. Cauda equina syndrome. Prog Neurobiol 2001; 64: 613-637. PMID: 11311464
27 Stodieck LS, Beel JA, Luttges MW. Structural properties of spinal nerve roots: protein composition. Exp Neurol. 1986 Jan; 91(1): 41-51.
28 Takenobu Y, Katsube N, Marsala M, Kondo K. Model of neuropathic intermittent claudication in the rat: methodology and application. J Neurosci Methods. 2001 Jan 15; 104(2): 191-8.
29 Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995 Feb; 12(1): 1-21. PMID: 7783230
30 Randall LO, Selitto JJ. A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodynam, 1957, 3: 409-419.
31 Eddy W B, Leimbach D. Synthetic analgesics: dithenylbutenyl and dithenylbutylamines. J Pharmacol Exp Ther, 1953, 107: 385-389.
32 Naylor A. Factors in the development of the spinal stenosis syndrome. J Bone Jt Surg Br Vol 1979; 61-B: 306-9.
33 Wilson CB. Significance of the small lumbar spinal canal: cauda equina compression syndromes due to spondylosis. 3: Intermittent claudication. J Neurosurg 1969; 31: 499-506.
34 Kawakami M, Tamaki T. Morphologic and quantitative changes in neurotransmitters in the lumbar spinal cord after acute or chronic mechanical compression of the cauda equina. Spine. 1992; 17(3 Suppl): S13-7. PMID: 1373525
35 Olmarker K, Rydevik B, Holm S. Edema formation in spinal nerve roots induced by experimental, graded compression. An experimental study on the pig cauda equina with special reference to differences in effects between rapid and slow onset of compression. Spine. 1989 Jun; 14(6): 569-73. PMID: 2546258
36 Olmarker K, Rydevik B. Pathophysiology of sciatica. Orthop Clin North Am. 1991 Apr; 22(2): 223-34. Review. PMID: 2014120
37 Spanos NC, Andrew J. Intermittent claudication and lateral lumbar disc protrusions. J Neurol, Neurosurg Psychiatry. 1966; 29: 273-7.
38 Naylor A. Factors in the development of the spinal stenosis syndrome. J Bone Jt Surg Br Vol 1979; 61-B: 306-9.
39 Wilson CB. Significance of the small lumbar spinal canal: cauda equina compression syndromes due to spondylosis. 3: Intermittent claudication. J Neurosurg 1969; 31: 499-506.
40 Zileli M, Schramm J.Motor versus somatosensory evoked potential changes after acute experimental spinal cord injury in rat .Acta Neurochir(wein), 1991, 108-l14.
41 Takenobu Y, Katsube N, Marsala M, Kondo K. Model of neuropathic intermittent claudication in the rat: methodology and application. J Neurosci Methods. 2001 Jan 15; 104(2): 191-8.
42 Sch?nstr?m N, Hansson T. Pressure changes following constriction of the cauda equina. An experimental study in situ. Spine. 1988; 13(4): 385-8. PMID: 3406845
43 Sch?nstr?m N, Bolender NF, Spengler DM, Hansson TH. Pressure changes within the cauda equina following constriction of the dural sac. An in vitro experimental study. Spine. 1984; 9(6): 604-7. PMID: 6495030
44 Schonstrom NS, Bolender NF, Spengler DM. The pathomorphology of spinal stenosis as seen on CT scans of the lumbar spine. Spine. 1985; 10(9): 806-11. PMID: 4089655
45 Schonstrom N, Hansson T. Pressure changes flowing constriction of the cauda equina: an experimental study in situ. Spine, 1988, 13 (4): 385.
46 Kim NH, Yang IH. A study of motor and sensory evoked potentials in chronic cauda equina compression of the dog. Eur Spine J. 1996; 5(5): 338-44. PMID: 8915640
47 Schonstrom N, Hansson T. Pressure changes following constriction of the cauda equina. An experimental study in situ. Spine. 1988 Apr; 13(4): 385-8. PMID: 3406845.
48 Schonstrom N, Bolender NF, Spengler DM, Hansson TH. Pressure changes within the cauda equina following constriction of the dural sac. An in vitro experimental study. Spine. 1984 Sep; 9(6): 604-7. PMID: 6495030
49 Effects of experimental graded compression on blood flow in spinal nerve roots. A vital microscopic study on the porcine cauda equina. Olmarker K, Rydevik B, Holm S, Bagge U. J Orthop Res. 1989; 7(6): 817-23. PMID: 2795321
50 Edema formation in spinal nerve roots induced by experimental, graded compression. An experimental study on the pig cauda equina with special reference to differences in effects between rapid and slow onset of compression. Olmarker K, Rydevik B, Holm S. Spine. 1989; 14(6): 569-73. PMID: 2546258
51 Experimental lumbar spinal stenosis. Analysis of the cortical evoked potentials, microvasculature, and histopathology. Delamarter RB, Bohlman HH, Dodge LD, Biro C. J Bone Joint Surg Am. 1990; 72(1): 110-20. PMID: 2295658
52 Yamaguchi K, Murakami M, Takahashi K, Moriya H, Tatsuoka H, Chiba T. Behavioral and morphologic studies of the chronically compressed cauda equina. Experimental model of lumbar spinal stenosis in the rat. Spine. 1999 May 1; 24(9): 845-51. PMID: 10327504
53 Takenobu Y, Katsube N, Marsala M, Kondo K. Model of neuropathic intermittent claudication in the rat: methodology and application. J Neurosci Methods. 2001; 104(2): 191-8. PMID: 11164245
54 Sekiguchi M, Kikuchi S, Myers RR. Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain. Spine. 2004; 29(10): 1105-11. PMID: 15131438
55 Ikawa M, Atsuta Y, Tsunekawa H. Ectopic firing due to artificial venous stasis in rat lumbar spinal canal stenosis model: a possible pathogenesis of neurogenic intermittent claudication. Spine. 2005; 30(21): 2393-7. PMID: 16261115
56 Anatomy of the Laboratory Rat. R. Hebel and M. W. Stromberg. Published by Burns &McEachern, Don Mills, Ontario. 1976.
57 Sekiguchi M, Kikuchi S, Myers RR. Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain. Spine. 2004; 29(10): 1105-11. PMID: 15131438
58 Yamaguchi K, Murakami M, Takahashi K, Moriya H, Tatsuoka H, Chiba T. Behavioral andmorphologic studies of the chronically compressed cauda equina. Experimental model of lumbar spinal stenosis in the rat. Spine. 1999 May 1; 24(9): 845-51. PMID: 10327504
59 Baker AR, Collins TA, Porter RW, Kidd C. Laser Doppler study of porcine cauda equina blood flow. The effect of electrical stimulation of the rootlets during single and double site, low pressure compression of the cauda equina. Spine. 1995 Mar 15; 20(6): 660-4. PMID: 7604341
60 Mao GP, Konno S, Arai I, Olmarker K, Kikuchi S. Chronic double-level cauda equina compression. An experimental study on the dog cauda equina with analyses of nerve conduction velocity. Spine. 1998 Aug 1; 23(15): 1641-4. PMID: 9704369
61 Porter RW, Ward D. Cauda equina dysfunction. The significance of two-level pathology. Spine. 1992 Jan; 17(1): 9-15. PMID: 1536018
62 Cheng H, Cao Yihai, Olson L. Spinal cord repair in adult paralegic rats: partial restoration of hind limb function. Science. 1996, 273(7): 510-513.
63 Gale K, Kerasidis H, Wrathall JR. Spinal cord contusion in the rat: behavioral analysis of functional neurologic impairment. Exp Ncurol. 1985; 132(2); 123-134.
64 Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in rat. J Neurosurg. 1977, 47(2): 577-581.
65 Tarlov IM, Klinger H, Vitale S. Spinal cord compression studies. 1. Expe rimental techniques to produce acute and gradual compression. AMA Arch Neural Psychiatry, 1953, 70(6): 813-819.
66 Fehlings MG. Tator CH. The relationship among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after expe rimental spinal cord injury. Exp Ncurol, 1995, 134(5): 220-228.
67 Hara M, Takayasu M, Watanabe K, Noda A, Takagi T, Suzuki Y, Yoshida J. Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats. J Neurosurg. 2000 Jul; 93(1 Suppl): 94-101.
68 LeMay DR, Neal S, Neal S, Zelenock GB, D'Alecy LG. Paraplegia in the rat induced by aortic cross-clamping: model characterization and glucose exacerbation of neurologic deficit. J Vasc Surg. 1987 Oct; 6(4): 383-90.
69 Reuter DG, Tacker WA Jr, Badylak SF, Voorhees WD 3rd, Konrad PE. Correlation of motor-evoked potential response to ischemic spinal cord damage. J Thorac Cardiovasc Surg. 1992 Aug; 104(2): 262-72.
70 Marsala M, Vanicky I, Yaksh TL. Effect of graded hypothermia (27 degrees to 34 degrees C) on behavioral function, histopathology, and spinal blood flow after spinal ischemia in rat. Stroke. 1994Oct; 25(10): 2038-46.
71 Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable Iocomtor rating scale for open field testing in rats. J Neurotraμma, 1995, 12(1): 1-12.
72 Basso DM, Beattie MS, Bresnahan JC. Graded histological and loc omotor outcomes after spinal cord contusion using the NY U weight-drop device verSUS transaction . Exp Ncurol, 1996, 139(6): 244. 256.
73 Farr TD, Liu L, Colwell KL, Whishaw IQ, Metz GA. Bilateral alteration in stepping pattern after unilateral motor cortex injury: a new test strategy for analysis of skilled limb movements in neurological mouse models. J Neurosci Methods. 2006; 153(1): 104-13. Epub 2005 Nov 22.
74 Bona E, Johansson BB, Hagberg H. Sensorimotor function and neuropathology five to six weeks after hypoxia-ischemia in seven-day-old rats . Pediatrics Research, 1997, 42(5): 678-683
75 Balduini W, De Angelis V, Mazzoni E, Cimino M. Long-lasting behavioral alterations following a hypoxic/ischemic brain injury in neonatal rats . Brain Res, 2000, 859(2): 318-325.
76 Jacobson GP, Tew JJ. Intraoperative EP monitoring. J Clin Neurophysiol, 1987; 4: 145
77 Delamarter RB. Bohlman HH, Dodge LD, et a1. Experimental lumbar spinal stenosis analysis of the cortical evoked potentials microvascμlature and histopathology. J Bone Joint Surg, 1990. 72A 1110.
78 Konno S, Arai I, Otani K, Olmarker K, Kikuchi S. Effects of beraprost sodium on canine cauda equina function and blood flow using a chronic spinal cord compression model. J Spinal Disord. 2001 Aug; 14(4): 336-8. PMID: 11481556
79 Watanabe R, Parke WW. Vascμlar and neural pathology of lumbosacral spinal stenosis. J Neurosrμg, 1986, 64: 64-70.
80 Hiraizumi Y, Transfeldt EE, Fujimaki E, Nakabayashi H, Ishikawa T, Sat OH. Electrophysiologic evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis. Spine, 1993, 18(10): 1355-60.
81 Experimental lumbar spine stenosls. J Bone Joint Surg. 1990, 72: 110-120.
82 Delamarter RB, Sherman JE, Carr JB. 1991 Volvo Award in experimental studies. Cauda equina syndrome: neurologic recovery following immediate, early, or late decompression. Spine. 1991 Sep; 16(9): 1022-9.
83 Olmarker K, Holm S, Rydevik B. Importance of compression onset rate for the degree of impairment of impulse propagation in experimental compression injury of the porcine cauda equina. Spine. 1990 May; 15(5): 416-9.
84 Dvonch V, Scarff T, Bunch WH, Smith D, Boscardin J, Lebarge H, Ibrahim K. Dermatomalsomatosensory evoked potentials: their use in lumbar radiculopathy. Spine. 1984 Apr; 9(3): 291-3. PMID: 6729594
85褚晓朝,陆裕朴,豫新智.诱发电位检查在周围神经损伤中的应用.中华骨科杂志. 1991, 11: 199-202.
86 Delamarter RB, Bohlman HH, Dodge LD, Biro C. Experimental lumbar spinal stenosis. Analysis of the cortical evoked potentials, microvasculature, and histopathology. J Bone Joint Surg Am. 1990 Jan; 72(1): 110-20.
87 Jespersen SM, Hansen ES, H?y K, Christensen KO, Lindblad BE, Ahrensberg J, Bünger C. Two-level spinal stenosis in minipigs. Hemodynamic effects of exercise. Spine. 1995 Dec 15; 20(24): 2765-73.
88 Kim NH. Yang IH. Song IK. Electrodiagnostic and histologic changes of graded caudal compression on cauda equina in dog . Spine. 1994. 19 l 1054. PMID: 8747257
89 Machida M, Asai T, Itagaki T. New approach for diagnosis and postoperative evaluation in herniated lumbosacral disc. Nippon Seikeigeka Gakkai Zasshi. 1984 Jan; 58(1): 1-10. Japanese. PMID: 6747397
90 Lehmkuhl-LD, Dimitrijevic-MR, Zidar-J. Lumbosacral evoked potentials (LSEPs) and cortical somatosensory evoked potentials (SEPs) in patients with lesions of the conus medμllaris and cauda equina. Electroencephalogr Clin Neurophysiol. 1988; 71(3) : 161-9
91 Gepstein-R, Brown-MD. Somatosensory-evoked potentials in lumbar nerve rootd ecompression. Clin Orthop. 1989 (245): 69-71
92 Fisher MA. SSEP in lumbar radiculopathy. Neurology. 1990; 40(2): 386-7.
93 Jones SJ, Edgar MA, Ransford AO. Sensory nerve conduction in the human spinal cord: epidural recordings made during scoliosis surgery. J Neurol Neurosurg Psychiatry. 1982 May; 45(5): 446-51. PMID: 6283032
94 SeyalM , Gabar AJ. The human posterior tibial somatosensory evoked potentials: synapse dependents and synapse independent spinal components. Electroencephalogrm Clin Neurophysiol, 1985, 62: 323.
95贺石生,侯铁胜,单晓巍,王建文,夏金辉,王吉.硬膜外移植自体髓核对大鼠神经根结构和功能的影响.第二军医大学学报. 2001; 22(05): 435-438.
96 Terada K, Larson BI, Owen JH, et al. The effect of nerve root lesioningon various somatosensory evoked potentials in the hog. Spine. 1993 Jun15; 18(8): 1090-5.
97 Molitor H. Somatosensory evoked potentials in root lesions and stenosis of the spinal canal (theirdiagnostic significance in clinical decision making). Neurosurg Rev. 1993; 16(1): 39-44.
98 Arunkumar MJ, Srinivasa Babu K, Chandy MJ. Motor and somatosensory evoked potentials in a primate model of experimental spinal cord injury. Neurol India. 2001 Sep; 49(3): 219-24. PMID: 11593236
99 Zileli M, Schramm J. Motor versus somatosensory evoked potential changes after acute experimental spinal cord injury in rats. Acta Neurochir (Wien). 1991; 108(3-4): 140-7. PMID: 2031473
100 Lee BH, Lee KH, Yoon DH, Kim UJ, Hwang YS, Park SK, Choi JU, Park YG. Effects of methylprednisolone on the neural conduction of the motor evoked potentials in spinal cord injured rats. J Korean Med Sci. 2005 Feb; 20(1): 132-8. PMID: 15716618
101 Owen J H, Bridwell KH, Shimon, et a1. Sensitivity and specificity of somatosensory and neurogenic motor evoked potentials i n animals and humans. Spine, 1988, 12: 1111.
102 Gillardon F, Klimaschewski L, Wickert H, et al. Expression pattern of candidate cell death effector proteins Bax, Bcl-2, Bcl-X, and c-Jun in sensory and motor neurons following sciatic nerve transection in the rat. Brain Res, 1996; 739(1-2): 244-250.
103 Tong JX, Rich KM. Diphenylpiperazine enhance regeneration after facial nerve injury. J Neurocytol, 1997. 26: 331-347.
104 Whiteside G, Doyle CA, Hunt SP, et a1. Diferential time course of neuronal and glial apoptosis in nenatal rat dorsal rot ganglia after sciatic nerve axotomy. Eur J Nosci, 1998, 10: 3400-3408.
105 Coggeshall RE, Lekam H, Doubell T, et a1. Central changes in primary aferent fibers following peripheral nerve lesion. Neurosei, 1997, 77: lll5-ll22.
106 Sekiguchi M, Kikuchi S, Myers RR. Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain. Spine. 2004 May 15; 29(10): 1105-11.
107 Kim NH, Yang IH, Song IK. Electrodiagnostic and histologic changes of graded caudal compression on cauda equina in dog. Spine, 1994, 19(9): 1054-62.
108 HirokawaN. Axonal transport and the cytoskeleton. Currr Opin Neurobiol, 1993, 3(5): 724.
109 Nixon RA. Curr Opin Cell Biol. The slow axonal transport of cytoskeletal proteins. 1998 Feb; 10(1): 87-92.
110 Allen RD, Weiss DG, Hayden JH, Brown DT, Fujiwake H, Simpson M. Gliding movement of and bidirectional transport along single native microtubules from squid axoplasm: evidence for an active role of microtubules in cytoplasmic transport. J Cell Biol. 1985 May; 100(5): 1736-52.
111Schnapp BJ, Vale RD, Sheetz MP, Reese TS. Single microtubules from squid axoplasm support bidirectional movement of organelles. Cell. 1985 Feb; 40(2): 455-62.
112 Zhao CQ, Jiang LS, Dai LY. Programmed cell death in intervertebral disc degeneration. Apoptosis. 2006 Dec; 11(12): 2079-88.
113 Yu J, Zhang L, Hwang P M, et a1. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell, 2001, 7(3): 673-682.
114 Han J, Flemington C, HoughtonA, et a1. Expression ofBbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc Natl Acad Sci USA, 2001, 98 (20): 11318-11323.
115徐晓,陈婉南,郑大利,黄清玲,林旭.肝细胞癌患者B和C基因型乙型肝炎病毒X蛋白的变异特点.癌症, 2004, 23(7): 756-761.
116 Chen L, Willis S N, Wei A, et a1. Diferential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell, 2005, 17(3): 393-403.
117 Culmsee C, Mattson MP. p53 in neuronal apoptosis. Biochem Biophys Res Commun. 2005 Jun 10; 331(3): 761-77. PMID: 15865932
118 Han J, Flemington C, Houghton AB, Gu Z, Zambetti GP, Lutz RJ, Zhu L, Chittenden T. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc Natl Acad Sci U S A. 2001 Sep 25; 98(20): 11318-23. PMID: 11572983
119 Yu J, Zhang L. No PUMA, no death: implications for p53-dependent apoptosis. Cancer Cell. 2003 Oct; 4(4): 248-9. PMID: 14585351
120 Jeffers JR, Rargans E, Lee Y, et al. PUMA is an essential mediator of p53-dependent and-independent apoptotic pathways. Cancer Cell, 2003, 4(4): 321-328.
121 Chipuk JE, Bouchier-Hayes L, Kuwana T, et al. PUMA couples the nuclear and cytopalsmic proapopotic function of p53. Science, 2005, 309(5741): 1732-1735.
122 Marzars G R, Jeanteur P, Lynch H T, et a1.Nucleotide sequence polymorphism in a hotspot mufion region the p53 gene.Oncogene, 1992, 7(4): 781-782.
123 Soussi T C, de Fmmental C, May P.Structural aspects ofthe r63 protein in relation to gene evlution.Oncogene, 1990, 5: 945- 952.
124 Lane DP. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2; 358(6381): 15-6. PMID: 1614522
125 Kastan M B, Zhan Q, Deity WS. et al. A mammalian cell cycle checkpoint pathway utilijing p53 and GADD45 is defective in ataxia-telangiectasia. Cel1. 1992, 71. 587.
126 Marx J. How p53 suppresses cell growth. Science, 1993, 262(1O): l644.
127 Steller H. Mechanisms and genes of cellular surcule. Scince, 1995, 267(5203): 1445-1449
128 Derry WB, Putzke AP, Rothman JH. Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance. Science. 2001 Oct 19; 294(5542): 591-5. Epub 2001 Sep 13. PMID: 11557844
129 Schuler M, Maurer U, Goldstein JC, Breitenbücher F, Hoffarth S, Waterhouse NJ, Green DR. p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation. Cell Death Differ. 2003 Apr; 10(4): 451-60. PMID: 12719722
130 Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX-and BAK-mediated mitochondrial apoptosis. Mol Cell. 2001 Sep; 8(3): 705-11. PMID: 11583631
131 Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005 Oct; 16(10): 4623-35. Epub 2005 Aug 3. PMID: 16079181
132 Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol. 2003 May; 23(9): 3173-85. PMID: 12697818
133 Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, Yao TP. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J. 2002 Nov 15; 21(22): 6236-45. PMID: 12426395
134 Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001 Oct 19; 107(2): 149-59. PMID: 11672523
2. Floman Y, Wiesel SW, Rothman RH. Cauda equina syndrome presenting as a herniated lumbar disk. Clin Orthop Relat Res 1980; 147: 234-237. PMID: 7371304
3. Byrne TN. Disorders of the spinal cord and cauda equina. Curr Opin Neurol Neurosurg 1993; 6: 545-548. PMID: 8400466
4. Shapiro S. Cauda equina syndrome secondary to lumbar disc herniation. Neurosurg 1993; 32: 743-747. PMID: 8492849
5. Kostuik JP, Harrington I, Alexander D, Rand W, Evans D. Cauda equina syndrome and lumbar disc herniation. J Bone Joint Surg Am 1986; 68: 386-391. PMID: 2936744
6. Lazarius A. Historia anatomica humani corporis. 1600, Becker: Frankfurt, Germany. 178.
7. Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 1934; 211: 210-215.
8. Mooney V. Differential diagnosis of low back disorders: principles of classification. In: Frymore JW, eds. The adult spine. New York: Raven Press; 1991: 1559-1560.
9. Shapiro S. Medical realities of cauda equina syndrome secondary to lumbar disc herniation. Spine 2000; 25: 348-352. PMID: 10703108
10. Gleave JR, Macfarlane R. Cauda equina syndrome: what is the relationship between timing of surgery and outcome? Br J Neurosurg 2002; 16: 325-328. PMID: 12389883
11. Gleave JR, MacFarlane R. Prognosis for recovery of bladder function following lumbar central disc prolapse. Br J Neurosurg 1990; 4: 205-209. PMID: 2397046
12. Raaf J. Removal of protruded lumbar intervertebral discs. J Neurosurg 1970; 32: 604-611. PMID: 5438104
13. Chang HS, Nakagawa H, Mizuno J. Lumbar herniated disc presenting with cauda equina syndrome. Long-term follow-up of four cases. Surg Neurol 2000; 53: 100-104. PMID: 10713185
14. O’Connell JE. Protrusions of the lumbar intervertebral discs: a clinical review based on five hundred cases treated by excision of the protrusion. J Bone Joint Surg Br 1951; 33: 8-30. PMID: 14814156
15. Kostuik JP. Medicolegal consequences of cauda equina syndrome: an overview. Neurosurg Focus 2004; 16: 39-41. PMID: 15202878
16. Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain. JAMA 1992; 268: 760-765. PMID: 1386391
17. Parke WW, Gammell K, Rothman RH. Arterial vascularization of the cauda equina. J Bone Joint Surg Am 1981; 63: 53-62. PMID: 7005240
18. Kou J, Fischgrund J, Biddinger A, Herkowitz H. Risk factors for spinal epidural hematoma after spinal surgery. Spine 2002; 27: 1670-1673. PMID: 12163731
19. Groen RJ, Ponssen H. The spontaneous spinal epidural hematoma. A study of the etiology. J Neurol Sci 1990; 98: 121-138. PMID: 2243224
20. Della-Giustina. Emergency department evaluation and treatment of back pain. Emerg Med Clin North Am 1999; 17: 877-893. PMID: 10584107
21. Kennedy JG, Soffe KE, McGrath A, Stephens MM, Walsh MG, McManus F. Predictors of outcome in cauda equina syndrome. Eur Spine J 1999; 8: 317-322. PMID: 10483835
22. Tay EC, Chacha PB. Midline prolapse of a lumbar intervertebral disc with compression of the cauda equina. J Bone Joint Surg Br 1979; 61: 43-46. PMID: 154521
23. Saint-Louis LA. Lumbar spinal stenosis assessment with computed tomography, magnetic resonance imaging, and myelography. Clin Orthop Relat Res 2001; 384: 122-136. PMID: 11249157
24. Bischoff RJ, Rodriguez RP, Gupta K, Righi A, Dalton JE, Whitecloud TS. A comparison of computed tomography-myelography, magnetic resonance imaging, and myelography in the diagnosis of herniated nucleus pulposus and spinal stenosis. J Spinal Disord 1993; 6: 289-295. PMID: 8219542
25. Modic MT, Masaryk T, Boumphrey F, Goormastic M, Bell G. Lumbar herniated disk disease and canal stenosis: prospective evaluation by surface coil MR, CT, and myelography. Am J Roentgenol 1986; 147: 757-765. PMID: 3489378
26. Kent DL, Haynor DR, Larson EB, Deyo RA. Diagnosis of lumbar spinal stenosis in adults: a metaanalysis of the accuracy of CT, MR, and myelography. Am J Roentgenol 1992; 158: 1135-1144. PMID: 1533084
27. Bundschuh CV, Modic MT, Ross JS, Masaryk TJ, Bohlman H. Epidural fibrosis and recurrent disk herniation in the lumbar spine: MR imaging assessment. Am J Roentgenol 1988; 150: 923-932. PMID: 3258108
28. Bell DA, Collie D, Statham PF. Cauda equina syndrome: what is the correlation between clinical assessment and MRI scanning? Br J Neurosurg 2007; 21: 201-203. PMID: 17453789
29. Tandon PN, Sankaren B. Cauda equina syndrome due to lumbar disc prolapse. Indian J Orthop 1967; 1: 112-116.
30. Shephard RH. Diagnosis and prognosis of cauda equina syndrome produced by protrusion oflumbar disk. Br Med J 1959; 2: 1434-1439. PMID: 14445833
31. Shi JG, Jia LS, Yuan W, Ye XJ, Chen DY, Ni B, et al. Clinical stages and early diagnosis of cauda equina syndrome due to lumbo-sacral nerve injury. Orthop J Chin (Chin) 2005; 7: 491-493.
32. Jaradeh S. Cauda equina syndrome: a neurologist's perspective. Reg Anesth 1993; 18(6 Suppl): 473-480. PMID: 8110650
33. OrendácováJ, CízkováD, Kafka J, LukácováN, Marsala M, Sulla I, et al. Cauda equina syndrome. Prog Neurobiol 2001; 64: 613-637. PMID: 11311464
34. Nakai K, Takenobu Y, Takimizu H, Akimaru S, Maegawa H, Ito H, et al. Effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model: comparison with nifedipine, ticlopidine and cilostazol. Prostaglandins Other Lipid Mediat 2003; 71: 253-263. PMID: 14518565
35. Murakami M, Takahashi K, Sekikawa T, Yasuhara K, Yamagata M, Moriya H. Effects of intravenous lipoprostaglandin E1 on neurogenic intermittent claudication. J Spinal Disord 1997; 10: 499-504. PMID: 9438815
36. Konno S, Kayama S, Olmarker K, Kikuchi S. Effects of OP-1206 (prostaglandin E1) on nerve-conduction velocity in the dog cauda equina subjected to acute experimental compression. J Spinal Disord 1996; 9: 103-106. PMID: 8793775
37. Yamamoto T, Shimoyama N, Asano H, Mizuguchi T. OP-1206, a prostaglandin E1 derivative, attenuates the thermal hyperesthesia induced by constriction injury to the sciatic nerve in the rat. Anesth Analg 1995; 80: 515-520. PMID: 7864417
38. Yone K, Sakou T, Kawauchi Y. The effect of Lipoprostaglandin E1 on cauda equina blood flow in patients with lumbar spinal canal stenosis: myeloscopic observation. Spinal Cord 1999; 37: 269-274. PMID: 10338347
39. Nakai K, Takenobu Y, Eguchi K, Takimizu H, Honjo K, Akimaru S, et al. The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model. Anesth Analg 2002; 94: 1537-1541. PMID: 12032022
40. Nakai K, Takenobu Y, Takimizu H, Akimaru S, Ito H, Maegawa H, et al. Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model. Prostaglandins Leukot Essent Fatty Acids 2003; 69: 269-273. PMID: 12907137
41. Koes BW, Scholten RJ, Mens JM, Bouter LM. Efficacy of non-steroidal anti-inflammatory drugs for low back pain: a systematic review of randomised clinical trials. Ann Rheum Dis 1997; 56: 214-223. PMID: 9165992
42. Pohjolainen T, Jekunen A, Autio L, Vuorela H. Treatment of acute low back pain with the COX-2-selective anti-inflammatory drug nimesulide: Results of a randomized, double-blind comparative trial versus ibuprofen. Spine 2000; 25: 1579-1585. PMID: 10851109
43. van Tulder MW, Scholten RJ, Koes BW, Deyo RA. Nonsteroidal anti-inflammatory drugs for low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group. Spine 2000; 25: 2501-2513. PMID: 11013503
44. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain: an updated cochrane review. Spine 2008; 33: 1766-1774. PMID: 18580547
45. Abram SE, O'Connor TC. Complications associated with epidural steroid injections. Reg Anesth 1996; 21: 149-162. PMID: 8829408
46. Fukusaki M, Kobayashi I, Hara T, Sumikawa K. Symptoms of spinal stenosis do not improve after epidural steroid injection. Clin J Pain 1998; 14: 148-151. PMID: 9647457
47. Hirata F, Schiffmann E, Venkatasubramanian K, Salomon D, Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci USA 1980; 77: 2533-2536. PMID: 6930649
48. Tsurufuji S, Sugio K, Takemasa F. The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone. Nature 1979; 280: 408-410. PMID: 460415
49. Vane J, Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs. FASEB J 1987; 1: 89-96. PMID: 3111928
50. Ardoin SP, Sundy JS. Update on nonsteriodal anti-inflammatory drugs. Curr Opin Rheumatol 2006; 18: 221-226. PMID: 16582683
51. Nakano M, Matsui H, Miaki K, Tsuji H. Postlaminectomy adhesion of the cauda equina: inhibitory effects of anti-inflammatory drugs on cauda equina adhesion in rats. Spine 1998;23: 298-304. PMID: 9507616
52. MacKay MA, Fischgrund JS, Herkowitz HN, Kurz LT, Hecht B, Schwartz M. The effect of interposition membrane on the outcome of lumbar laminectomy and discectomy. Spine 1995; 20: 1793-1796. MID: 7502136
53. Einhaus SL, Robertson JT, Dohan FC Jr, Wujek JR, Ahmad S. Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L). Spine 1997; 22: 1440-1447. PMID: 9231961
54. Sandoval MA, Hernandez-Vaquero D. Preventing peridural fibrosis with nonsteroidal anti-inflammatory drugs. Eur Spine J 2008; 17: 451-455. PMID: 18172695
55. Jacobs RR, McClain O, Neff J. Control of postlaminectomy scar formation: an experimental and clinical study. Spine 1980; 5: 223-229. PMID: 7394661
56. Bartels RH, de Vries J. Hemi-cauda equina syndrome from herniated lumbar disc: a neurosurgical emergency? Can J Neurol Sci 1996: 23; 296-299. PMID: 8951209
57. Jones DL, Moore T. The types of neuropathic bladder dysfunction associated with prolapsed lumbar intervertebral discs. Br J Urol 1973; 45: 39-43. PMID: 4690149
58. Nielsen B, de Nully M, Schmidt K, Hansen RI. A urodynamic study of cauda equina syndrome due to lumbar disc herniation. Urol Int 1980; 35: 167-170. PMID: 7385464
59. DeLong WB, Polissar N, Neradilek B. Timing of surgery in cauda equina syndrome with urinary retention: meta-analysis of observational studies. J Neurosurg Spine 2008; 8: 305-320. PMID: 18377315
60. Mangialardi R, Mastorillo G, Minoia L, Garofalo R, Conserva F, Solarino GB. Lumbar disc herniation and cauda equina syndrome. Considerations on a pathology with different clinical manifestations. Chir Organi Mov 2002; 87: 35-42. PMID: 12198948
61. McLaren AC, Bailey SI. Cauda equina syndrome: a complication of lumbar discectomy. Clin Orthop Relat Res 1986; 204: 143-149. PMID: 3956005
62. Hellstr?m P, Kortelainen P, Kontturi M. Late urodynamic findings after surgery for cauda equina syndrome caused by a prolapsed lumbar intervertebral disk. J Urol 1986; 135: 308-312. PMID: 3944866
63. Ahn UM, Ahn NU, Buchowski JM, Garrett ES, Sieber AN, Kostuik JP. Cauda equina syndrome secondary to lumbar disc herniation: a meta-analysis of surgical outcomes. Spine 2000; 25: 1515-1522. PMID: 10851100
64. Thongtrangan I, Le H, Park J, Kim DH. Cauda equina syndrome in patients with low lumbar fractures. Neurosurg Focus 2004; 16: e6. PMID: 15202876
65. Kohles SS, Kohles DA, Karp AP, Erlich VM, Polissar NL. Time-dependent surgical outcomes following cauda equina syndrome diagnosis: comments on a meta-analysis. Spine 2004; 29: 1281-1287. PMID: 15167669
66. Hussain SA, Gullan RW, Chitnavis BP. Cauda equina syndrome: outcome and implications for management. Br J Neurosurg 2003; 17: 164-167. PMID: 12820760
67. Qureshi A, Sell P. Cauda equina syndrome treated by surgical decompression: the influence of timing on surgical outcome. Eur Spine J 2007; 16: 2143-2151. PMID: 17828560
68. Buchner M, Schiltenwolf M. Cauda equina syndrome caused by intervertebral lumbar disk prolapse: mid-term results of 22 patients and literature review. Orthopedics 2002; 25: 727-731.PMID: 12138958
69. Borovich B, Zaaroor M, Gruszkiewicz J. The syndrome of the central L-3-herniated disc with special emphasis on motor involvement. Acta Neurochir (Wien) 1984; 70: 115-125. PMID: 6741627
70. McCarthy MJ, Aylott CE, Grevitt MP, Hegarty J. Cauda equina syndrome: factors affecting long-term functional and sphincteric outcome. Spine 2007; 32: 207-216. PMID: 17224816
71. Jensen RL. Cauda equina syndrome as a postoperative complication of lumbar spine surgery. Neurosurg Focus. 2004; 16: e7. PMID: 15202877
72. Foo D, Rossier AB. Preoperative neurological status in predicting surgical outcome of spinal epidural hematomas. Surg Neurol 1981; 15: 389-401. PMID: 9760981
73. Deyo RA, Cherkin DC, Loeser JD, Biqos SJ, Ciol MA. Morbidity and mortality in association with operations on the lumbar spine. The influence of age, diagnosis, and procedure. J Bone Joint Surg Am 1992; 74: 536-543. PMID: 1583048
74. Bohlman HH, Kirkpatrick JS, Delamarter RB, Leventhal M. Anterior decompression for late pain and paralysis after fractures of the thoracolumbar spine. Clin Orthop Relat Res 1994; 300: 24-29. PMID: 8131342
75. Schaeffer HR. Cauda equina compression resulting from massive lumbar disc extrusion. Aust N Z J Surg 1966; 35: 300-306. PMID: 5220085
76. Ramirez LF, Thisted R. Complications and demographic characteristics of patients undergoing lumbar discectomy in community hospitals. Neurosurgery 1989; 25: 226-231. PMID: 2770987
77. Lenehan B, Sullivan P, Street J, Dudeney S. Epidural abscess causing cauda equina syndrome. Ir J Med Sci 2005; 174: 88-91. PMID: 16285347
78. Reihsaus E, Waldbaur H, Seeling W. Spinal epidural abscess: a meta-analysis of 915 patients. Neurosurg Rev 2000; 23: 175-205. PMID: 11153548
79. Rigamonti D, Liem L, Sampath P, Knoller N, Namaguchi Y, Schreibman DL, et al. Spinal epidural abscess: contemporary trends in etiology, evaluation, and management. Surg Neurol 1999; 52: 189-197. PMID: 10447289
80. Tang HJ, Lin HJ, Liu YC, Li CM. Spinal epidural abscess-experience with 46 patients and evaluation of prognostic factors. J Infect 2002; 45: 76-81. PMID: 12217707
81. Yilmaz C, Selek HY, Gürkan I, Erdemli B, Korkusuz Z. Anterior instrumentation for the treatment of spinal tuberculosis. J Bone Joint Surg Am 1999; 81: 1261-1267. PMID: 10505522
82. Govender S, Parbhoo AH. Support for the anterior column with allografts in tuberculosis of the spine. J Bone Joint Surg Br 1998; 81: 106-109. PMID: 10068015
83. Cohen DB. Infectious origins of cauda equina syndrome. Neurosurg Focus 2004; 16: e2. PMID: 15202872
84. Faraj A, Krishna M, Mehdian SM. Cauda equina syndrome secondary to lumbar spondylodiscitis caused by streptococcus milleri. Eur Spine J 1996; 5: 134-136. PMID: 8724196
85. Brecker SJ, Pugey CD. Nocardia asteroides infection of the cauda equina. J Neurol Neurosurg Psychiatry 1988; 51: 309-311. PMID: 3346704
86. Kapoor SK, Garg V, Dhaon BK, Jindal M. Tuberculosis of the posterior vertebral elements: a rare cause of compression of the cauda equina. A case report. J Bone Joint Surg Am 2005; 87: 391-394. PMID: 15687164
87. Carod-Artal FJ. Neurological complications of Schistosoma infection. Trans R Soc Trop Med Hyg 2008; 102: 107-16. PMID: 17905371
88. Chen HJ, Liang CL, Lu K, Liliang PC, Tsai YD. Cauda equina syndrome caused by delayed traumatic spinal subdural haematoma. Injury 2001; 32: 505-507. PMID: 11476820
89. Harrop JS, Hunt GE Jr, Vaccaro AR. Conus medullaris and cauda equina syndrome as a result of traumatic injuries: management principles. Neurosurg Focus 2004; 16: e4. PMID: 15202874
90. Schoenecker PL, Cole HO, Herring JA, Capelli AM, Bradford DS. Cauda equina syndrome after in situ arthrodesis for severe spondylolisthesis at the lumbosacral junction. J Bone Joint Surg Am 1990; 72: 369-377. PMID: 2312532
91. Cheung EV, Herman MJ, Cavalier R, Pizzutillo PD. Spondylolysis and spondylolisthesis in children and adolescents: II. Surgical management. J Am Acad Orthop Surg 2006; 14(8): 488-498. PMID: 16885480
92. Shaw M, Birch N. Facet joint cysts causing cauda equina compression. J Spinal Disord Tech 2004; 17: 442-445. PMID: 15385886
93. Ahn NU, Ahn UM, Nallamshetty L, Springer BD, Buchowski JM, Funches L, et al. Cauda equina syndrome in ankylosing spondylitis (the CES-AS syndrome): meta-analysis of outcomes after medical and surgical treatments. J Spinal Disord 2001; 14: 427-433. PMID: 11586143
94. Tullous MW, Skerhut HE, Story JL, Brown WE Jr, Eidelberg E, Dadsetan MR, et al. Cauda equina syndrome of long-standing ankylosing spondylitis. Case report and review of the literature. J Neurosurg 1990; 73: 441-447. PMID: 2200856
95. Johnsson KE, Sass M. Cauda equina syndrome in lumbar spinal stenosis: case report and incidence in Jutland, Denmark. J Spinal Disord Tech. 2004 Aug; 17: 334-5. PMID: 15280766
96. Schatzker J, Pennal GF. Spinal stenosis, a cause of cauda equina compression. J Bone Joint Surg Br 1968; 50: 606-618. PMID: 4235812
97. Storm PB, Chou D, Tamargo RJ. Lumbar spinal stenosis, cauda equina syndrome, and multiple lumbosacral radiculopathies. Phys Med Rehabil Clin N Am 2002; 13: 713-733. PMID: 12380555
98. Rubenstein DJ, Ghelman B. Case report 477: Cauda equina syndrome (CES) complicating long-standing ankylosing spondylitis (AS). Skeletal Radiol 1988; 17: 212-215. PMID: 3375851
99. Baba H, Maezawa Y, Furusawa N, Imura S, Tomita K. The role of calcium deposition in the ligamentum flavum causing a cauda equina syndrome and lumbar radiculopathy. Paraplegia 1995; 33: 219-223. PMID: 7609980
100. Jauslin PA, Müller AF, Myers P, Velebit V. Cauda equina syndrome associated with an aorto-caval fistula. Eur J Vasc Surg 1991; 5: 471-473. PMID: 1915914
101. Henriques T, Olerud C, Petrén-Mallmin M, Ahl T. Cauda equina syndrome as a postoperative complication in five patients operated for lumbar disc herniation. Spine 2001; 26: 293-297. PMID: 11224866
102. Dimopoulos V, Fountas KN, Machinis TG, Feltes C, Chung I, Johnston K, et al. Postoperative cauda equina syndrome in patients undergoing single-level lumbar microdiscectomy. Report of two cases. Neurosurg Focus 2005; 19: e11. PMID: 16122210
103. Str?mqvist B, J?nsson B, Annertz M, Holt?s S. Cauda equina syndrome caused by migrating fat graft after lumbar spinal decompression. A case report demonstrated with magnetic resonance imaging. Spine 1991; 16: 100-101. PMID: 2003232
104. Prusick VR, Lint DS, Bruder WJ. Cauda equina syndrome as a complication of free epidural fat-grafting. A report of two cases and a review of the literature. J Bone Joint Surg Am. 1988 Sep; 70: 1256-1258. PMID: 3417714
105. Mayer PJ, Jacobsen FS. Cauda equina syndrome after surgical treatment of lumbar spinal stenosis with application of free autogenous fat graft. A report of two cases. J Bone Joint Surg Am. 1989; 71: 1090-1093. PMID: 2760085
106. Onik G, Maroon JC, Jackson R. Cauda equina syndrome secondary to an improperly placed nucleotome probe. Neurosurgery 1992; 30: 412-415. PMID: 1620307
107. Dickman CA, Shedd SA, Spetzler RF, Shetter AG, Sonntag VK. Spinal epidural hematoma associated with epidural anesthesia: complications of systemic heparinization in patients receiving peripheral vascular thrombolytic therapy. Anesthesiology 1990; 72: 947-950. PMID: 2339809
108. Liu YC, Wu RS, Wong CS. Unexpected complication of attempted epidural anaesthesia: cauda equina syndrome. Anaesth Intensive Care 2003; 31: 461-464. PMID: 12973972
109. Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, et al. Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 1991; 72: 275-281. PMID: 1994754
110. Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier F, et al. Complications of regional anesthesia in France: the SOS regional anesthesia hotline service. Anesthesiology 2002; 97: 1274-1280. PMID: 12411815
111. Oppenheim JS, Spitzer DE, Segal DH. Nonvascular complications following spinal manipulation. Spine J 2005; 5: 660-667. PMID: 16291108
112. Marhouitz HD, Dloce DT. Cauda equina syndrome due to sequestrated recurrent disk herniation after chiropractic manipulation. Orthopedics 1997; 20: 652-653. PMID: 9243679
113. Haldeman S, Rubinstein SM. Cauda equina syndrome in patients undergoing manipulation of the lumbar spine. Spine 1992; 17: 1469-1473. PMID: 1471004
114. Simou N, Zioga A, Zygouris A, Pahatouridis D, Charalabopoulos K, Batistatou A. Plexiform neurofibroma of the cauda equina: a case report and review of the literature. Int J Surg Pathol 2008; 16: 78-80. PMID: 18203792
115. Gaetani P, Di Ieva A, Colombo P, Tancioni F, Aimar E, Debernardi A, et al. Intradural spinal metastasis of renal clear cell carcinoma causing cauda equina syndrome. Acta Neurochir (Wien) 2004; 146: 857-861. PMID: 15254809
116. Lampl Y, Eshel Y, Gilad R, Sarova-Pinchas I. Glioblastoma multiforme with bone metastase and cauda equina syndrome. J Neurooncol 1990; 8: 167-172. PMID: 2162916
117. Bagley CA, Gokaslan ZL. Cauda equina syndrome caused by primary and metastatic neoplasms. Neurosurg Focus 2004; 16: e3. PMID: 15202873
118. Kotil K, Kilinc BM, Bilge T. Spinal metastasis of occult lung carcinoma causing cauda equina syndrome. J Clin Neurosci 2007; 14: 372-375. PMID: 17336230
119. Poncelet A. The neurologic complications of Paget's disease. J Bone Miner Res 1999; 14(Suppl 2): 88-91. PMID: 10510221
120. Richter RL, Semble EL, Turner RA, Challa VR. An unusual manifestation of Paget's disease of bone: spinal epidural hematoma presenting as acute cauda equina syndrome. J Rheumatol 1990; 17: 975-978. PMID: 2213767
121. Frenay J, Lambooy N. Cauda equina syndrome following spondylolisthesis by low lumbar involvement of chronic rheumatoid arthritis. Neurochirurgie 1974; 20: 431-440. PMID: 4468381
122. Kawaji H, Miyamoto M, Gembun Y, Ito H. A case report of rapidly progressing cauda equina symptoms due to rheumatoid arthritis. J Nippon Med Sch 2005; 72: 290-294. PMID: 16247229
123. Sant SM, O'Connell D. Cauda equina syndrome in ankylosing spondylitis: a case report and review of the literature. Clin Rheumatol 1995; 14: 224-226. PMID: 7789067
124. Schr?der R, Urbach H, Zierz S. Cauda equina syndrome with multiple lumbar diverticulacomplicating long-standing ankylosing spondylitis. Clin Investig 1994; 72: 1056-1059. PMID: 7711415
125. Groen RJ, Ponssen H. The spontaneous spinal epidural hematoma: a study of the etiology. J Neurol Sci 1990; 98: 121-138. PMID: 2243224
126. Mohit AA, Fisher DJ, Matthews DC, Hoffer E, Avellino AM. Inferior vena cava thrombosis causing acute cauda equina syndrome. Case report. J Neurosurg 2006; 104(1 Suppl): 46-49. PMID: 16509481
127. Domenicucci M, Ramieri A, Ciappetta P, Delfini R. Nontraumatic acute spinal subdural hematoma: report of five cases and review of the literature. J Neurosurg 1999; 91(1 Suppl): 65-73. PMID: 10419371
128. Morandi X, Riffaud L, Chabert E, Brassier G. Acute nontraumatic spinal subdural hematomas in three patients. Spine 2001; 26: E547-551. PMID: 11725255
129. Russell NA, Benoit BG. Spinal subdural hematoma. A review. Surg Neurol 1983; 20: 133-137. PMID: 6879409
1贾连顺主编.现代脊柱外科学.北京.人民军医出版社. 2007; 865-875.
2 Mooney V. Differential Diagnosis of Low Back Disorders. Principles of classification. In: J. W. Frymore, editor in chief. Raven Press, Lt. d, New York. The Adult Spine. 1991; 1559-60.
3 Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain. JAMA 1992; 268(6):760-765.
4 Kostuik JP, Harrington I, Alexander D, Rand W, Evans D. Cauda equina syndrome and lumbar disc herniation. J Bone Joint Surg Am, 1986; 68: 386-391.
5 Shapiro S. Cauda equina syndrome secondary to lumbar disc herniation. Neurosurg 1993; 32(3): 743-747.
6 Shapiro S. Medical realities of cauda equina syndrome secondary to lumbar disc herniation. Spine. 2000; 25(3):348-51; discussion 352.
7 Gleave JR, Macfarlane R. Cauda equina syndrome: what is the relationship between timing of surgery and outcome? Br J Neurosurg 2002; 16(4):325-328.
8 Gleave JR, MacFarlane R. Prognosis for recovery of bladder function following lumbar central disc prolapse. Br J Neurosurg 1990; 4(3):205-209.
9 Raaf J. Removal of protruded lumbar intervertebral discs. J Neurosurg 1970; 32(5):604-611.
10 Chang HS, Nakagawa H, Mizuno J. Lumbar herniated disc presenting with cauda equina syndrome. Long-term followup of four cases. Surg Neurol 2000; 53(2):100-104.
11 O’Connell JE. Protrusions of the lumbar intervertebral discs: a clinical review based on five hundred cases treated by excision of the protrusion. J Bone Joint Surg Br 1951; 33:8-30.
12 Kostuik JP. Medicolegal consequences of cauda equina syndrome: an overview. Neurosurg Focus 2004; 16:39-41.
13史建刚,贾连顺,李家顺,蔡凯华,刘颜玲,倪灿荣,贾宁阳.第二军医大学学报. 2003; 24(01):83-86.
14史建刚,贾连顺,苟三怀,肖建如,叶晓健,谭军,陈雄生,贾宁阳。神经根损害神经根后根节病理变化的实验研究。中国矫形外科杂志, 2002; 10(13): 1317-1318.
15王金武,侯春林,陈爱民,王诗波,赵良宇. SD大鼠马尾与骶神经根的解剖学观察.中国临床解剖学杂志, 2003; 21(4): 368-370.
16 Anatomy of the Laboratory Rat. R. Hebel and M. W. Stromberg. Published by Burns &McEachern, Don Mills, Ontario. 1976.
17 Yagi J, Sμmino R. Inhibition of a hyperpolarization-activated current by clonidine in rat dorsal rootganglion neurons. J Neurophysiol. 1998; 80(3): 1094-104.
18 Olmarker K. Spinal nerve root compression. Nutrition and function of the porcine cauda equina compressed in vivo. Acta Orthop Scand Suppl. 1991; 242: 1-27.
19 Olmarker K, Holm S, Rosenqvist AL, Rydevik B. Experimental nerve root compression. A model of acute, graded compression of the porcine cauda equina and an analysis of neural and vascular anatomy. Spine. 1991 Jan; 16(1): 61-9.
20 Inman DM, Steward O. Physical size does not determine the unique hIst0path0l0gical response seen in the injured mouse spinal cord. J Neurotraμma, 2003, 20(1): 33-42.
21 Hedrich HJ: History, strains and models. In: Krinke GJ eds. The laboratory rat. London & San Diego: Academic Press, 2000: 3-16.
22 Metz GA, Curt A, van de Meent H. et a1. Validation of the weightdrop contusion model in rats: a comparative study of human spinal cord injury. J Neurotraμma, 2000, 17(1): 1-17.
23 Rauschning W, Bergstr?m K, Pech P. Correlative craniospinal anatomy studies by computed tomography and cryomicrotomy. J Comput Assist Tomogr. 1983 Feb; 7(1): 9-13. PMID: 6826854
24 Parke WW, Gammell K, Rothman RH. Arterial vascularization of the cauda equina. J Bone Joint Surg Am. 1981 Jan; 63(1): 53-62. PMID: 7005240
25 Parke WW. Intrinsic vasculature of the lumbosacral spinal nerve roots. Orthopedics. 1991 Apr; 14(4): 455-7.
26 OrendácováJ, CízkováD, Kafka J, LukácováN, Marsala M, Sulla I, et al. Cauda equina syndrome. Prog Neurobiol 2001; 64: 613-637. PMID: 11311464
27 Stodieck LS, Beel JA, Luttges MW. Structural properties of spinal nerve roots: protein composition. Exp Neurol. 1986 Jan; 91(1): 41-51.
28 Takenobu Y, Katsube N, Marsala M, Kondo K. Model of neuropathic intermittent claudication in the rat: methodology and application. J Neurosci Methods. 2001 Jan 15; 104(2): 191-8.
29 Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995 Feb; 12(1): 1-21. PMID: 7783230
30 Randall LO, Selitto JJ. A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodynam, 1957, 3: 409-419.
31 Eddy W B, Leimbach D. Synthetic analgesics: dithenylbutenyl and dithenylbutylamines. J Pharmacol Exp Ther, 1953, 107: 385-389.
32 Naylor A. Factors in the development of the spinal stenosis syndrome. J Bone Jt Surg Br Vol 1979; 61-B: 306-9.
33 Wilson CB. Significance of the small lumbar spinal canal: cauda equina compression syndromes due to spondylosis. 3: Intermittent claudication. J Neurosurg 1969; 31: 499-506.
34 Kawakami M, Tamaki T. Morphologic and quantitative changes in neurotransmitters in the lumbar spinal cord after acute or chronic mechanical compression of the cauda equina. Spine. 1992; 17(3 Suppl): S13-7. PMID: 1373525
35 Olmarker K, Rydevik B, Holm S. Edema formation in spinal nerve roots induced by experimental, graded compression. An experimental study on the pig cauda equina with special reference to differences in effects between rapid and slow onset of compression. Spine. 1989 Jun; 14(6): 569-73. PMID: 2546258
36 Olmarker K, Rydevik B. Pathophysiology of sciatica. Orthop Clin North Am. 1991 Apr; 22(2): 223-34. Review. PMID: 2014120
37 Spanos NC, Andrew J. Intermittent claudication and lateral lumbar disc protrusions. J Neurol, Neurosurg Psychiatry. 1966; 29: 273-7.
38 Naylor A. Factors in the development of the spinal stenosis syndrome. J Bone Jt Surg Br Vol 1979; 61-B: 306-9.
39 Wilson CB. Significance of the small lumbar spinal canal: cauda equina compression syndromes due to spondylosis. 3: Intermittent claudication. J Neurosurg 1969; 31: 499-506.
40 Zileli M, Schramm J.Motor versus somatosensory evoked potential changes after acute experimental spinal cord injury in rat .Acta Neurochir(wein), 1991, 108-l14.
41 Takenobu Y, Katsube N, Marsala M, Kondo K. Model of neuropathic intermittent claudication in the rat: methodology and application. J Neurosci Methods. 2001 Jan 15; 104(2): 191-8.
42 Sch?nstr?m N, Hansson T. Pressure changes following constriction of the cauda equina. An experimental study in situ. Spine. 1988; 13(4): 385-8. PMID: 3406845
43 Sch?nstr?m N, Bolender NF, Spengler DM, Hansson TH. Pressure changes within the cauda equina following constriction of the dural sac. An in vitro experimental study. Spine. 1984; 9(6): 604-7. PMID: 6495030
44 Schonstrom NS, Bolender NF, Spengler DM. The pathomorphology of spinal stenosis as seen on CT scans of the lumbar spine. Spine. 1985; 10(9): 806-11. PMID: 4089655
45 Schonstrom N, Hansson T. Pressure changes flowing constriction of the cauda equina: an experimental study in situ. Spine, 1988, 13 (4): 385.
46 Kim NH, Yang IH. A study of motor and sensory evoked potentials in chronic cauda equina compression of the dog. Eur Spine J. 1996; 5(5): 338-44. PMID: 8915640
47 Schonstrom N, Hansson T. Pressure changes following constriction of the cauda equina. An experimental study in situ. Spine. 1988 Apr; 13(4): 385-8. PMID: 3406845.
48 Schonstrom N, Bolender NF, Spengler DM, Hansson TH. Pressure changes within the cauda equina following constriction of the dural sac. An in vitro experimental study. Spine. 1984 Sep; 9(6): 604-7. PMID: 6495030
49 Effects of experimental graded compression on blood flow in spinal nerve roots. A vital microscopic study on the porcine cauda equina. Olmarker K, Rydevik B, Holm S, Bagge U. J Orthop Res. 1989; 7(6): 817-23. PMID: 2795321
50 Edema formation in spinal nerve roots induced by experimental, graded compression. An experimental study on the pig cauda equina with special reference to differences in effects between rapid and slow onset of compression. Olmarker K, Rydevik B, Holm S. Spine. 1989; 14(6): 569-73. PMID: 2546258
51 Experimental lumbar spinal stenosis. Analysis of the cortical evoked potentials, microvasculature, and histopathology. Delamarter RB, Bohlman HH, Dodge LD, Biro C. J Bone Joint Surg Am. 1990; 72(1): 110-20. PMID: 2295658
52 Yamaguchi K, Murakami M, Takahashi K, Moriya H, Tatsuoka H, Chiba T. Behavioral and morphologic studies of the chronically compressed cauda equina. Experimental model of lumbar spinal stenosis in the rat. Spine. 1999 May 1; 24(9): 845-51. PMID: 10327504
53 Takenobu Y, Katsube N, Marsala M, Kondo K. Model of neuropathic intermittent claudication in the rat: methodology and application. J Neurosci Methods. 2001; 104(2): 191-8. PMID: 11164245
54 Sekiguchi M, Kikuchi S, Myers RR. Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain. Spine. 2004; 29(10): 1105-11. PMID: 15131438
55 Ikawa M, Atsuta Y, Tsunekawa H. Ectopic firing due to artificial venous stasis in rat lumbar spinal canal stenosis model: a possible pathogenesis of neurogenic intermittent claudication. Spine. 2005; 30(21): 2393-7. PMID: 16261115
56 Anatomy of the Laboratory Rat. R. Hebel and M. W. Stromberg. Published by Burns &McEachern, Don Mills, Ontario. 1976.
57 Sekiguchi M, Kikuchi S, Myers RR. Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain. Spine. 2004; 29(10): 1105-11. PMID: 15131438
58 Yamaguchi K, Murakami M, Takahashi K, Moriya H, Tatsuoka H, Chiba T. Behavioral andmorphologic studies of the chronically compressed cauda equina. Experimental model of lumbar spinal stenosis in the rat. Spine. 1999 May 1; 24(9): 845-51. PMID: 10327504
59 Baker AR, Collins TA, Porter RW, Kidd C. Laser Doppler study of porcine cauda equina blood flow. The effect of electrical stimulation of the rootlets during single and double site, low pressure compression of the cauda equina. Spine. 1995 Mar 15; 20(6): 660-4. PMID: 7604341
60 Mao GP, Konno S, Arai I, Olmarker K, Kikuchi S. Chronic double-level cauda equina compression. An experimental study on the dog cauda equina with analyses of nerve conduction velocity. Spine. 1998 Aug 1; 23(15): 1641-4. PMID: 9704369
61 Porter RW, Ward D. Cauda equina dysfunction. The significance of two-level pathology. Spine. 1992 Jan; 17(1): 9-15. PMID: 1536018
62 Cheng H, Cao Yihai, Olson L. Spinal cord repair in adult paralegic rats: partial restoration of hind limb function. Science. 1996, 273(7): 510-513.
63 Gale K, Kerasidis H, Wrathall JR. Spinal cord contusion in the rat: behavioral analysis of functional neurologic impairment. Exp Ncurol. 1985; 132(2); 123-134.
64 Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in rat. J Neurosurg. 1977, 47(2): 577-581.
65 Tarlov IM, Klinger H, Vitale S. Spinal cord compression studies. 1. Expe rimental techniques to produce acute and gradual compression. AMA Arch Neural Psychiatry, 1953, 70(6): 813-819.
66 Fehlings MG. Tator CH. The relationship among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after expe rimental spinal cord injury. Exp Ncurol, 1995, 134(5): 220-228.
67 Hara M, Takayasu M, Watanabe K, Noda A, Takagi T, Suzuki Y, Yoshida J. Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats. J Neurosurg. 2000 Jul; 93(1 Suppl): 94-101.
68 LeMay DR, Neal S, Neal S, Zelenock GB, D'Alecy LG. Paraplegia in the rat induced by aortic cross-clamping: model characterization and glucose exacerbation of neurologic deficit. J Vasc Surg. 1987 Oct; 6(4): 383-90.
69 Reuter DG, Tacker WA Jr, Badylak SF, Voorhees WD 3rd, Konrad PE. Correlation of motor-evoked potential response to ischemic spinal cord damage. J Thorac Cardiovasc Surg. 1992 Aug; 104(2): 262-72.
70 Marsala M, Vanicky I, Yaksh TL. Effect of graded hypothermia (27 degrees to 34 degrees C) on behavioral function, histopathology, and spinal blood flow after spinal ischemia in rat. Stroke. 1994Oct; 25(10): 2038-46.
71 Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable Iocomtor rating scale for open field testing in rats. J Neurotraμma, 1995, 12(1): 1-12.
72 Basso DM, Beattie MS, Bresnahan JC. Graded histological and loc omotor outcomes after spinal cord contusion using the NY U weight-drop device verSUS transaction . Exp Ncurol, 1996, 139(6): 244. 256.
73 Farr TD, Liu L, Colwell KL, Whishaw IQ, Metz GA. Bilateral alteration in stepping pattern after unilateral motor cortex injury: a new test strategy for analysis of skilled limb movements in neurological mouse models. J Neurosci Methods. 2006; 153(1): 104-13. Epub 2005 Nov 22.
74 Bona E, Johansson BB, Hagberg H. Sensorimotor function and neuropathology five to six weeks after hypoxia-ischemia in seven-day-old rats . Pediatrics Research, 1997, 42(5): 678-683
75 Balduini W, De Angelis V, Mazzoni E, Cimino M. Long-lasting behavioral alterations following a hypoxic/ischemic brain injury in neonatal rats . Brain Res, 2000, 859(2): 318-325.
76 Jacobson GP, Tew JJ. Intraoperative EP monitoring. J Clin Neurophysiol, 1987; 4: 145
77 Delamarter RB. Bohlman HH, Dodge LD, et a1. Experimental lumbar spinal stenosis analysis of the cortical evoked potentials microvascμlature and histopathology. J Bone Joint Surg, 1990. 72A 1110.
78 Konno S, Arai I, Otani K, Olmarker K, Kikuchi S. Effects of beraprost sodium on canine cauda equina function and blood flow using a chronic spinal cord compression model. J Spinal Disord. 2001 Aug; 14(4): 336-8. PMID: 11481556
79 Watanabe R, Parke WW. Vascμlar and neural pathology of lumbosacral spinal stenosis. J Neurosrμg, 1986, 64: 64-70.
80 Hiraizumi Y, Transfeldt EE, Fujimaki E, Nakabayashi H, Ishikawa T, Sat OH. Electrophysiologic evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis. Spine, 1993, 18(10): 1355-60.
81 Experimental lumbar spine stenosls. J Bone Joint Surg. 1990, 72: 110-120.
82 Delamarter RB, Sherman JE, Carr JB. 1991 Volvo Award in experimental studies. Cauda equina syndrome: neurologic recovery following immediate, early, or late decompression. Spine. 1991 Sep; 16(9): 1022-9.
83 Olmarker K, Holm S, Rydevik B. Importance of compression onset rate for the degree of impairment of impulse propagation in experimental compression injury of the porcine cauda equina. Spine. 1990 May; 15(5): 416-9.
84 Dvonch V, Scarff T, Bunch WH, Smith D, Boscardin J, Lebarge H, Ibrahim K. Dermatomalsomatosensory evoked potentials: their use in lumbar radiculopathy. Spine. 1984 Apr; 9(3): 291-3. PMID: 6729594
85褚晓朝,陆裕朴,豫新智.诱发电位检查在周围神经损伤中的应用.中华骨科杂志. 1991, 11: 199-202.
86 Delamarter RB, Bohlman HH, Dodge LD, Biro C. Experimental lumbar spinal stenosis. Analysis of the cortical evoked potentials, microvasculature, and histopathology. J Bone Joint Surg Am. 1990 Jan; 72(1): 110-20.
87 Jespersen SM, Hansen ES, H?y K, Christensen KO, Lindblad BE, Ahrensberg J, Bünger C. Two-level spinal stenosis in minipigs. Hemodynamic effects of exercise. Spine. 1995 Dec 15; 20(24): 2765-73.
88 Kim NH. Yang IH. Song IK. Electrodiagnostic and histologic changes of graded caudal compression on cauda equina in dog . Spine. 1994. 19 l 1054. PMID: 8747257
89 Machida M, Asai T, Itagaki T. New approach for diagnosis and postoperative evaluation in herniated lumbosacral disc. Nippon Seikeigeka Gakkai Zasshi. 1984 Jan; 58(1): 1-10. Japanese. PMID: 6747397
90 Lehmkuhl-LD, Dimitrijevic-MR, Zidar-J. Lumbosacral evoked potentials (LSEPs) and cortical somatosensory evoked potentials (SEPs) in patients with lesions of the conus medμllaris and cauda equina. Electroencephalogr Clin Neurophysiol. 1988; 71(3) : 161-9
91 Gepstein-R, Brown-MD. Somatosensory-evoked potentials in lumbar nerve rootd ecompression. Clin Orthop. 1989 (245): 69-71
92 Fisher MA. SSEP in lumbar radiculopathy. Neurology. 1990; 40(2): 386-7.
93 Jones SJ, Edgar MA, Ransford AO. Sensory nerve conduction in the human spinal cord: epidural recordings made during scoliosis surgery. J Neurol Neurosurg Psychiatry. 1982 May; 45(5): 446-51. PMID: 6283032
94 SeyalM , Gabar AJ. The human posterior tibial somatosensory evoked potentials: synapse dependents and synapse independent spinal components. Electroencephalogrm Clin Neurophysiol, 1985, 62: 323.
95贺石生,侯铁胜,单晓巍,王建文,夏金辉,王吉.硬膜外移植自体髓核对大鼠神经根结构和功能的影响.第二军医大学学报. 2001; 22(05): 435-438.
96 Terada K, Larson BI, Owen JH, et al. The effect of nerve root lesioningon various somatosensory evoked potentials in the hog. Spine. 1993 Jun15; 18(8): 1090-5.
97 Molitor H. Somatosensory evoked potentials in root lesions and stenosis of the spinal canal (theirdiagnostic significance in clinical decision making). Neurosurg Rev. 1993; 16(1): 39-44.
98 Arunkumar MJ, Srinivasa Babu K, Chandy MJ. Motor and somatosensory evoked potentials in a primate model of experimental spinal cord injury. Neurol India. 2001 Sep; 49(3): 219-24. PMID: 11593236
99 Zileli M, Schramm J. Motor versus somatosensory evoked potential changes after acute experimental spinal cord injury in rats. Acta Neurochir (Wien). 1991; 108(3-4): 140-7. PMID: 2031473
100 Lee BH, Lee KH, Yoon DH, Kim UJ, Hwang YS, Park SK, Choi JU, Park YG. Effects of methylprednisolone on the neural conduction of the motor evoked potentials in spinal cord injured rats. J Korean Med Sci. 2005 Feb; 20(1): 132-8. PMID: 15716618
101 Owen J H, Bridwell KH, Shimon, et a1. Sensitivity and specificity of somatosensory and neurogenic motor evoked potentials i n animals and humans. Spine, 1988, 12: 1111.
102 Gillardon F, Klimaschewski L, Wickert H, et al. Expression pattern of candidate cell death effector proteins Bax, Bcl-2, Bcl-X, and c-Jun in sensory and motor neurons following sciatic nerve transection in the rat. Brain Res, 1996; 739(1-2): 244-250.
103 Tong JX, Rich KM. Diphenylpiperazine enhance regeneration after facial nerve injury. J Neurocytol, 1997. 26: 331-347.
104 Whiteside G, Doyle CA, Hunt SP, et a1. Diferential time course of neuronal and glial apoptosis in nenatal rat dorsal rot ganglia after sciatic nerve axotomy. Eur J Nosci, 1998, 10: 3400-3408.
105 Coggeshall RE, Lekam H, Doubell T, et a1. Central changes in primary aferent fibers following peripheral nerve lesion. Neurosei, 1997, 77: lll5-ll22.
106 Sekiguchi M, Kikuchi S, Myers RR. Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain. Spine. 2004 May 15; 29(10): 1105-11.
107 Kim NH, Yang IH, Song IK. Electrodiagnostic and histologic changes of graded caudal compression on cauda equina in dog. Spine, 1994, 19(9): 1054-62.
108 HirokawaN. Axonal transport and the cytoskeleton. Currr Opin Neurobiol, 1993, 3(5): 724.
109 Nixon RA. Curr Opin Cell Biol. The slow axonal transport of cytoskeletal proteins. 1998 Feb; 10(1): 87-92.
110 Allen RD, Weiss DG, Hayden JH, Brown DT, Fujiwake H, Simpson M. Gliding movement of and bidirectional transport along single native microtubules from squid axoplasm: evidence for an active role of microtubules in cytoplasmic transport. J Cell Biol. 1985 May; 100(5): 1736-52.
111Schnapp BJ, Vale RD, Sheetz MP, Reese TS. Single microtubules from squid axoplasm support bidirectional movement of organelles. Cell. 1985 Feb; 40(2): 455-62.
112 Zhao CQ, Jiang LS, Dai LY. Programmed cell death in intervertebral disc degeneration. Apoptosis. 2006 Dec; 11(12): 2079-88.
113 Yu J, Zhang L, Hwang P M, et a1. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell, 2001, 7(3): 673-682.
114 Han J, Flemington C, HoughtonA, et a1. Expression ofBbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc Natl Acad Sci USA, 2001, 98 (20): 11318-11323.
115徐晓,陈婉南,郑大利,黄清玲,林旭.肝细胞癌患者B和C基因型乙型肝炎病毒X蛋白的变异特点.癌症, 2004, 23(7): 756-761.
116 Chen L, Willis S N, Wei A, et a1. Diferential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell, 2005, 17(3): 393-403.
117 Culmsee C, Mattson MP. p53 in neuronal apoptosis. Biochem Biophys Res Commun. 2005 Jun 10; 331(3): 761-77. PMID: 15865932
118 Han J, Flemington C, Houghton AB, Gu Z, Zambetti GP, Lutz RJ, Zhu L, Chittenden T. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc Natl Acad Sci U S A. 2001 Sep 25; 98(20): 11318-23. PMID: 11572983
119 Yu J, Zhang L. No PUMA, no death: implications for p53-dependent apoptosis. Cancer Cell. 2003 Oct; 4(4): 248-9. PMID: 14585351
120 Jeffers JR, Rargans E, Lee Y, et al. PUMA is an essential mediator of p53-dependent and-independent apoptotic pathways. Cancer Cell, 2003, 4(4): 321-328.
121 Chipuk JE, Bouchier-Hayes L, Kuwana T, et al. PUMA couples the nuclear and cytopalsmic proapopotic function of p53. Science, 2005, 309(5741): 1732-1735.
122 Marzars G R, Jeanteur P, Lynch H T, et a1.Nucleotide sequence polymorphism in a hotspot mufion region the p53 gene.Oncogene, 1992, 7(4): 781-782.
123 Soussi T C, de Fmmental C, May P.Structural aspects ofthe r63 protein in relation to gene evlution.Oncogene, 1990, 5: 945- 952.
124 Lane DP. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2; 358(6381): 15-6. PMID: 1614522
125 Kastan M B, Zhan Q, Deity WS. et al. A mammalian cell cycle checkpoint pathway utilijing p53 and GADD45 is defective in ataxia-telangiectasia. Cel1. 1992, 71. 587.
126 Marx J. How p53 suppresses cell growth. Science, 1993, 262(1O): l644.
127 Steller H. Mechanisms and genes of cellular surcule. Scince, 1995, 267(5203): 1445-1449
128 Derry WB, Putzke AP, Rothman JH. Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance. Science. 2001 Oct 19; 294(5542): 591-5. Epub 2001 Sep 13. PMID: 11557844
129 Schuler M, Maurer U, Goldstein JC, Breitenbücher F, Hoffarth S, Waterhouse NJ, Green DR. p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation. Cell Death Differ. 2003 Apr; 10(4): 451-60. PMID: 12719722
130 Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX-and BAK-mediated mitochondrial apoptosis. Mol Cell. 2001 Sep; 8(3): 705-11. PMID: 11583631
131 Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005 Oct; 16(10): 4623-35. Epub 2005 Aug 3. PMID: 16079181
132 Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol. 2003 May; 23(9): 3173-85. PMID: 12697818
133 Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, Yao TP. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J. 2002 Nov 15; 21(22): 6236-45. PMID: 12426395
134 Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001 Oct 19; 107(2): 149-59. PMID: 11672523