Epileptic Seizures Following Cortical Application of Fibrin Sealants Containing Tranexamic Acid in Rats

Summary  Background. Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS.  Method. FS containing aprotinin or different concentrations of tAMCA (0.5–47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia.  Findings. FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity.  Interpretation. Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.     

Effect of Acrylamide on Neurological Recovery Following Spinal Cord Injury in Rats

Summary  Acrylamide (ACR) is a cumulative neurotoxin which causes axonal degeneration in animals and man. Industrial workers exposed to ACR have been reported to suffer from a variety of central and peripheral neuropathological symptoms including numbness of hands and feet, skin peeling and muscular weakness of legs. These reports suggest that the body burden of ACR may be a risk factor in recovery patterns following neurotrauma. The present study was designed to assess the effect of ACR on neurological recovery following spinal cord injury (SCI) in rats.  Male Sprague-Dawley rats weighing 200–230 g were anaesthetised with chloral hydrate and laminectomy was performed at T 7–8 level leaving the dura intact. A compression plate (2.2×5.0 mm) loaded with a weight of 35 g was placed on the exposed cord for 5 minutes. Animals were divided into seven groups of eight rats each. The animals in Group 1 served as control whereas rats in Group 2 underwent laminectomy alone (sham). The rats in Group 3 to 6 were subjected to SCI as mentioned above. Animals in Groups 4, 5 and 6 also received ACR in the doses of 10 mg/kg, 20 mg/kg and 40 mg/kg, i.p., respectively in addition to SCI, whereas the rats in Group 7 received ACR alone at a dose of 40 mg/kg body weight. The first dose of ACR was given 30 minutes before SCI, followed by daily administration of drug for 7 days. Post traumatic neurological recovery was recorded daily for 10 days using a modified Tarlov score, inclined plane test and sensory and vocal score. Electrophysiological changes were assessed using somatosensory and corticomotor evoked potentials. The animals were sacrificed at different time intervals and the injured site of the spinal cord was analysed for lipid hydroperoxides (LPH), conjugated dienes (CD) and glutathione (GSH). Neuropathological changes in the spinal cord were assessed using light microscopy. The rats exposed to compression injury alone showed a maximum neurological deficit at 24 hr and then a gradual recovery was observed over a period of 10 days. The rats treated with ACR along with SCI showed poor or no recovery over a period of 10 days. Our electrophysiological and histopathological studies also confirmed that concomitant exposure to ACR produces a significant deleterious effect on the recovery from SCI. SCI induced increase in oxidative stress (increase in LPH and CD and decrease in GSH) is also exacerbated by ACR suggesting a role of free radicals.  The results of this study suggest that increased body burden of ACR may retard the recovery from neurotrauma or even lead to permanent disability.     

应用激光多普勒血流仪监测兔急性脊髓缺血损伤后腰髓血流动力学变化及病理学观察的研究

目的：应用激光多普勒血流仪监测兔脊髓缺血再灌流后腰髓血流的动态性变化，讨论腰髓血流的动力学特点。方法：通过阻断腹主动脉，造成脊髓腰尾段缺血。按缺血和再灌流各时间段分别连续测定腰髓血流变化。取缺血前、缺血４０分钟、再灌流４小时局部脊髓行组织病理和透射电镜检查。结果：在缺血４０分钟腰髓局部血灌流量迅速下降至基线值的－８１．５７％（Ｐ值＝２．０１Ｅ－１７）。再灌流时，局部血流迅速增高并超过基线水平。再灌流１０分钟，局部血灌流量与基线的百分比变化值为５７．９８％（Ｐ值＝３．３Ｅ－０７）。随后逐渐降低，再灌流１小时后，局部血灌流量基本恢复基线水平（３．９７％，Ｐ值＝０．５５７８９９）。以后血灌流量低于基线水平，出现缺血后延迟性低灌流。直至再灌流４小时（－２３．５％，Ｐ值＝１．８４Ｅ－０３）低灌流保持相对稳定，血流未见恢复。缺血４０分钟，有明确病理学改变；再灌流４小时后，病理学改变明显进一步加重。结论：上述结果对于脊髓缺血性损伤后继发性功能障碍提供了理论依据。     

阿司匹林对大鼠脊髓损伤细胞凋亡的保护作用

目的 观察阿司匹林对大鼠慢性压迫性脊髓损伤后神经细胞凋亡及神经功能恢复的影响。方法选择65只体重为220～250g的Wistar大鼠（雌雄不限），于T10部位置入后路渐进式压迫装置，制作成慢性压迫性脊髓损伤模型。随机分为阿司匹林治疗组（A组，30只）、生理盐水对照组（B组，30只）和假手术组（C组，5只）。应用原位末端脱氧核糖核苷酸转移酶介导dUTP标记技术，分别于慢性压迫性脊髓损伤后1、3、7、14、28d做行为学评价，并取材对脊髓损伤区进行细胞凋亡检测。结果A、B组均发现细胞凋亡，A组与B组细胞凋亡率相比差异有显著性（P〈0．05），A组与B组行为学评价相比差异有显著性（P〈0．05），神经细胞凋亡情况与运动功能改变具有相关性。结论 阿司匹林对慢性脊髓压迫损伤后所导致的神经细胞凋亡产生抑制作用。     

Quantitative Computed Tomography in the Evaluation of Spinal Osteoporosis Following Spinal Cord Injury

Disuse osteoporosis occurs in the lower extremities of patients with spinal cord injury (SCI). However, spinal osteoporosis is not usually observed in these patients. We investigated lumbar spine bone mineral density (BMD) in SCI patients using single energy quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA). Our study population consisted of 64 patients with long-standing SCI. Spine BMD (g/cm³) was assessed by QCT at four vertebrae ranging from T11 to L4 with single midvertebral CT slices 1 cm thick parallel to the vertebral end-plates. Confounding variables affecting normal trabecular bone pattern, such as compression fractures, surgical hardware or fat replacement, were excluded. For a subset of 29 patients, DXA values of the spine and femoral neck were also measured, and QCT and DXA Z-scores were compared On the average, the 64 SCI patients had Z-scores 2.0 ± 1.2 below those of age-matched controls. In the subset of 29 patients with both QCT and DXA measurements, the QCT and DXA Z-scores were 2.4 ± 1.1 below and 1.3 ± 2.3 above the mean, respectively (p<0.0001). Our results indicate that QCT reveals osteoporosis of the spine after SCI, in contrast to DXA. We postulate that QCT is more valuable for evaluating spinal osteoporosis following SCI than DXA and thus recommend QCT for spinal BMD studies in SCI. Received: 20 December 1999 / Accepted: 17 April 2000     

2型糖尿病大鼠后肢缺血模型的建立及评价

目的建立2型糖尿病大鼠后肢缺血模型并进行评价,为后续的干预实验提供研究平台。方法将15只SD大鼠随机分为正常对照组、糖尿病组及糖尿病后肢缺血组,每组5只。糖尿病组及糖尿病后肢缺血组的10只大鼠均给予高脂饮食喂养4周后,腹腔注射链脲佐菌素（STZ,40mg／kg）以建立2型糖尿病模型。糖尿病后肢缺血组大鼠建模成功后行双侧髂总动脉结扎术以建立后肢缺血模型,正常对照组和糖尿病组大鼠仅分离髂总动脉,不予结扎。2周后对3组大鼠股动脉的起始段行彩色多普勒超声检查,以检测股动脉的血流峰值速度和血流加速时间;取缺血部位的小腿三头肌及大腿股四头肌组织,分别行HE染色及免疫组化SP染色,以观察3组大鼠肌细胞的营养状况及血管再生情况。结果后肢缺血模型建模2周后,正常对照组、糖尿病组和糖尿病后肢缺血组大鼠的血流峰值速度分别为（22．49±3．02）cm／s、（17．36±2．60）cm／s和（11．23±1．26）cm／s,血流加速时间分别为（0．080±0．009）S、（0．120±0．009）S和（0．160±0．020）s,糖尿病后肢缺血组大鼠的股动脉血流峰值速度小于正常对照组和糖尿病组（P〈0．05）,而血流加速时间较长（P〈0．05）。HE染色结果显示：糖尿病后肢缺血组大鼠小腿三头肌的结构破坏,有大量炎症细胞浸润,肌肉损伤程度重于正常对照组和糖尿病组。免疫组化sP染色结果显示：糖尿病后肢缺血组大鼠大腿股四头肌的毛细血管密度[（1．40±0．55）个／HPF]小于正常对照组[（6．80±0．84）个／HPF]及糖尿病组[（4．60±0．55）个／HPF],差异均有统计学意义伊〈O．05）。结论对SD大鼠给予高脂饮食联合小剂量STZ注射可以成功诱导2型糖尿病模型,在此模型基础上结扎髂总动脉可以成功制备糖尿病后肢缺血模型。     

胶质源性神经营养因子对脊髓损伤后功能及前角运动神经元酶组织化学改变的研究

目的　探讨胶质细胞源性神经营养因子 (GDNF)对损伤脊髓运动功能及前角运动神经元酶组织化学改变的影响。方法　改良Allen撞击致T13 脊髓不完全损伤 ,蛛网膜下腔分别给予生理盐水和GDNF ,不同时间分别 :①测定大鼠后肢神经功能 ;②利用酶组织化学染色方法显示脊髓侧前角运动神经元中胆碱酯酶 (ChE)和酸性磷酸酶 (ACP)活性并通过计算机图像分析系统将酶活性量化、比较。结果　①神经功能随时间延长而逐渐恢复 ,GDNF有助于功能恢复 ,但 3周时均未达正常标准 ;②ChE和ACP活性随时间延长而向正常趋近 ,GDNF显著加强了这一趋势 ;③随着ChE水平上升和ACP水平隆低 ,大鼠后肢运动功能逐渐恢复 ,两者呈现较强的相关性。结论　①前角运动神经元酶学改变与神经功能恢复密切相关 ;②GDNF加强前角运动神经元酶学改变 ,呈现对损伤神经元有保护作用。     

大鼠脊髓损伤松质骨神经SP免疫反应性的变化

目的：探讨脊髓损伤后大鼠松质骨中神经末梢P物质（SubstanceP,SP)免疫反应性的变化及在脊髓损伤（Spin al Cord Injury,SCI)后骨代谢变化中的意义。方法：3月龄SD大鼠60只随机均分为SCI组与对照组，SCI组于T10处完全横断脊髓；对照组仅行椎板切除术，术后1、3、6周处死动物测定血钙，碱性磷酸酶，尿钙、尿机苷；对股骨髁松质骨行SP免疫组化染色，结合计算机图像分析系统对SP免疫阳性神经的染色强度进行定量分析。结果：血尿生化结果SCI组各时间段骨吸收显著增强；分布于小梁骨内的SP阳性神经的免疫反应性在1、3周组显著增高与对照组比较差异显著。结论：SCI后松质骨内SP的增加可能与SCI早期破骨性骨吸收增强有关。     

Motor Function Changes in the Rat Following Severe Spinal Cord Injury

Systemic hypothermia exerts neuroprotective effects following trauma and ischemia caused by vascular occlusion in the brain. In the spinal cord similar effects have been demonstrated following ischemia after aortic occlusion. We have previously presented protective effects on several morphological parameters in the early period after the injury, using an established spinal cord compression injury model and systemic hypothermia. In the present study we have evaluated the effects on motor function following severe spinal cord compression trauma and treatment with moderate systemic hypothermia. Thirty Sprague Dawley rats were randomized into three groups: In group 1 (n = 4), the animals underwent a hypothermic procedure, including a 2 h hypothermic period with a body temperature of 30 degrees C, following the initial laminectomy. In group 2 (n = 12) a 50 g compression was applied to the spinal cords for 5 min, after which the animals were kept under normothermic anesthesia for 3 h. In group 3 (n = 14), the animals underwent the same trauma procedure as in group 2 and the same hypothermic procedure as in group 1. The animals were allowed to survive for 14 days, during which the motor function was recorded. This degree of trauma results in a non-reversible paraplegia, and the addition of systemic hypothermia as described above did not alter the neurological recovery as measured by two different methods of recording the motor function up to two weeks after injury. All animals survived in group 1. However, the mortality rates in group 2 were 25% and in group 3, 50%, respectively, which mirrors the severity of the trauma. The application of systemic hypothermia and the lack of experimental therapeutic success highlight the difficulties of transferring experimental beneficial neuroprotective effects to a clinically useful treatment method. In this experimental set-up the effects of the severe primary injury may overshadow the effects of the secondary injury mechanisms, which limits the therapeutic possibilities of systemic hypothermic treatment.     

脊髓半切损伤模型的制备

目的：建立一种简便易行、稳定可靠的脊髓半切伤动物模型。方法：取大鼠C5-7颈髓阶段，T8—ll胸髓阶段直径1/2脊髓半切。术后不同时间观察脊髓组织学变化，并纪录脊髓神经功能综合评分(CBS)。结果：光镜下半切脊髓远端侧索和灰质神经变性坏死，术后24h、1周实验组CBS评分与假手术组有显著意义(P＜0．05)，且脊髓腹角运动神经元与假手术组比较明显变化，行为表现为大鼠运动和感觉功能障碍。结论：颈髓5—7半切模型死亡率低，安全可靠。     

Prognostic Significance of the Delayed Plantar Reflex Following Spinal Cord Injury

Abstract

The delayed plantar reflex (DPR) is a pathologic flexor variant which requires unusually strong stimulation of the sole of the foot and is characterized by a prolonged interval between the stimulus and the response, slow and protracted plantarflexion of the great toe and/or other toes and slow return to the neutral position. The purpose of this study was to evaluate prospectively the functional outcome of spinal cord injury (SCI) patients based on the presence or absence of a DPR immediately following injury. Thirty-six subjects were evaluated within one week of injury. A complete neurological evaluation following American Spinal Injury Association (ASIA) standards was performed and the presence or absence of a DPR was noted on admission. Ambulation status and ASIA Impairment Scales were recorded at discharge from the rehabilitation unit and the data were analyzed by the Chi-square method with Yates’ correction for continuity. The data demonstrated a high correlation of the DPR with motor complete injuries (p <0.01) and a poor prognosis for recovery of ambulation (p <0.01). Clinicians should recognize this abnormal reflex, which may be used in conjunction with a complete neurological examination, to help prognosticate future function in the acute SCI patient. (J Spinal Cord Med 1997; 20:207-211)     

Diffusion of Tranexamic Acid to the Joint

Tranexamic acid (Cyklokapron, Kabi, Stockholm) in a dose of 10 mg per kg body weight was given i.v. to 17 patients at various intervals before operation on the knee joint, in order to elucidate the diffusion of the drug to the joint fluid and the synovial membrane. The acid diffused rapidly to both the above tissues, and in the joint fluid it reached the same concentration as in the serum. The biologic half-time in the joint fluid was about 3 hours. in the treatment of joint bleedings in hemophiliacs and in association with intra-articular operations on such patients tranexamic acid is a suitable supplement to conventional substitution therapy.     

Diffusion of Tranexamic Acid to the Joint

Tranexamic acid (Cyklokapron, Kabi, Stockholm) in a dose of 10 mg per kg body weight was given i.v. to 17 patients at various intervals before operation on the knee joint, in order to elucidate the diffusion of the drug to the joint fluid and the synovial membrane. The acid diffused rapidly to both the above tissues, and in the joint fluid it reached the same concentration as in the serum. The biologic half-time in the joint fluid was about 3 hours. in the treatment of joint bleedings in hemophiliacs and in association with intra-articular operations on such patients tranexamic acid is a suitable supplement to conventional substitution therapy.     

脊髓损伤后大鼠骨细胞形态学特点

目的：探讨脊髓损伤(Spinal Cord Injury,SCI)后大鼠骨细胞形态学变化特点及在SCI后骨代谢改变中的意义。方法：20只3个月龄SD大鼠均分为SCI组与对照组。SCI组于T10椎体处完全横断脊髓；对照组仅行椎板切除术，6周后处死动物取材。透射电镜观察股骨近段超微结构。原位凋亡染色法计数股骨近段骨细胞凋亡指数。结果：SCI组骨细胞有4种改变：(1)细胞器减少，骨陷窝增大，絮状物质增多、凝聚以及骨陷窝壁嗜锇板层形成等骨细胞性溶骨表现；(2)退变相骨细胞表现为胞质和细胞器出现严重囊性改变如线粒体空泡化，细胞壁不完整，细胞器不清晰；(3)出现核固缩，细胞处于崩解状态为坏死的形态学改变；(4)异染色质凝集、边聚，细胞出芽起泡等典型凋亡样改变。SCI组小梁骨中骨细胞凋亡指数显著高于对照组(P＜0．01)。结论：骨细胞的溶骨、退变、坏死和凋亡样改变是SCI后骨细胞的形态学特征，也可能是SCI后骨代谢偶联失调的细胞学基础。     

自体和异体神经组织联合移植修复脊髓损伤的实验研究

目的：探讨神经组织联合移植对成鼠急性脊髓损伤的修复能力。方法：成年雌性Ｗｉｓｔａｒ鼠３６只随机分为３组,损伤Ｔ１－３脊髓左后柱,移植孕１４ｄ胚胎脊髓（ＦＳＣ组１５只）或带血管正中神经加胚胎脊髓（Ｖ＋Ｆ组１５只）,另６只做对照组。术后８周行体感诱发电位、光、电镜和免疫组化检查。结果：Ｖ＋Ｆ组胚胎组织体积增长速度、神经纤维和神经元数目显著高于ＦＳＣ组（Ｐ〈０．０１）,细胞大多分化较好,有少数类似运动神     

胚胎脊髓移植后大鼠损伤脊髓c-Jun免疫反应的变化及其意义

目的：研究大鼠胚胎脊髓移植后能否影响,c-Hun免疫反应的表达和脊髓损伤后大鼠功能的恢复,方法;将动物分为脊髓半切洞损伤加胚胎脊髓移植组（A组）和单纯脊髓板切洞损伤加明胶海绵填塞组（B组）,每个时相点每组6只动物,术只1,3,7,14和28天,应用行为学和电生理检查观察大鼠功能恢复情况,应用免疫细胞化学方法,c-Jun免疫反应的表达,采用计算机图像分析技术,进行定量分析。结果：大鼠脊髓损伤后c-Jun免疫反应的表达A组明显高于B组,胚胎脊髓抑制后可使损伤脊髓高表达c-Jun 免疫反应持续到术后7天,增加的c-Jun免疫反应阳性细胞数目与神经功能的改善相平行。结论：胚胎脊髓移植后可使损伤脊髓高表达c-Jun,并促进大鼠功能恢复。     

磷脂酶A2硬膜外腔注射对大鼠腰髓及背根节中CGRP含量的影响

目的探讨腰椎间盘突出症相关腰腿痛发病的可能机制.方法在大鼠的硬膜外腔注射磷脂酶A2,免疫组化的方法测定大鼠背根节和脊髓后角中CGRP的变化.结果硬膜外腔注射磷脂酶A2后,L4-6背根节中CGRP阳性神经元的数目和面积明显增加,脊髓背角浅层中CGRP阳性神经纤维终末的面积也明显增加.证实与对照组相比较有显著性差别(P＜0.05).结论磷脂酶A2是一种疼痛伤害性刺激,它可能在腰椎间盘突出相关腰腿痛的发病中起到重要的作用.