The effects of fetal allogeneic umbilical cord tissue transplant following experimental spinal cord injury on urinary bladder morphology

Background and purposeIn continuation of our previous experimental study on spinal cord injury (SCI) using fetal stem cells, we investigated here the effects of fetal allogeneic umbilical cord tissue transplant on the urinary bladder morphology in a rat SCI model.Material and methodsFive pregnant albino Wistar rats at 12 days of gestation were used to obtain the umbilical cord cell graft. In Group 1 (n = 5), Th8-Th9 laminectomy was performed. Group 2 (n = 5) received spinal cord injury. In Group 3 (n = 5), the cultured fetal umbilical cord cells coated with alginate gel were placed into the lesion cavity. In Group 4 (n = 5), only alginate sponges without umbilical cord cells were placed into the injury cavity. The bladders of animals were analyzed pathologically at 21 days after surgery.ResultsThe thickness of the epithelium and the lamina propria did not differ among studied groups (p > 0.05). The lamina muscularis thickness was significantly higher in Group 2 and Group 4 than the others (p < 0.05). The bladder weight was similar among Groups 1, 2, and 3 (p > 0.05). Fibrosis was significantly increased in Group 2 (p < 0.05); it was greater in Group 2 than in Group 3 (p < 0.05) but did not differ between Groups 1 and 3 (p > 0.05).ConclusionsThis study suggests that allogeneic umbilical cord tissue transplantation after SCI may prevent bladder wall hypertrophy and fibrosis in the rat SCI model.     

Cross-cultural adaptation and reliability evaluation of Iranian version of Functional Assessment Measure in spinal cord injury patients

Background and purposeThe aim of this study was to translate and validate the Iranian version of the Functional Assessment Measure (FAM) among patients with spinal cord injury (SCI).Material and methodsTwo hundred patients with SCI participated in this study. A convenience sampling approach was used for selection of the patients. The FAM was translated into Persian language and then independently translated back into English. The reliability of the FAM was assessed by test-retest methods with a 14-day interval for interrater reliability. Intraclass correlation coefficient (ICCs) was calculated and interrater reliability and intrarater reliability were assessed.ResultsThe mean age of the patients was 35.7 years (SD, 7.2) and 86% of patients were male. The Cronbach alpha coefficient for both raters was above 0.70. Intrarater reliability of the Iranian version of the FAM ranged from good to excellent agreement. The highest level of intrarater reliability was observed for Community mobility (ICC = 0.93). There was good to excellent agreement for interrater reliability of the FAM. The FAM could differentiate between subgroups of patients based on the level of injury but not for the time elapsed from the injury.ConclusionsBased on the results of this study, the Iranian version of the FAM (FAM-Ir) was highly valid and reliable for evaluation of functional ability in patients with SCI. Therefore, we would suggest that the FAM could also be used as an assessment tool for SCI patients.     

Results of intraoperative neurophysiological monitoring in spinal canal surgery

Background and purposeSpine surgery carries the risk of neurological complications. Neurophysiological intraoperative monitoring (NIOM) plays some role in preventing adverse events. NIOM is a young technique, and because of its costs and additional personnel it requires constant evaluation of indications. Nowadays, it is generally assumed that if available, NIOM should be used in every intracanal surgical procedure. This study aimed to evaluate the efficacy and indications for NIOM in spine surgery in relation to procedure location.Material and methodsEffectiveness of NIOM in spinal canal surgery was evaluated by comparison of the number of neurological complications in patients treated surgically with and without NIOM. A total of 74 consecutive patients were surgically treated for spinal canal pathology at the Department of Neurosurgery, 10^th Military Hospital in Bydgoszcz. Thirty-eight patients operated on with the use of NIOM were compared to a historic population of 36 patients treated before the introduction of NIOM. The number of patients with neurological complications was analyzed in three groups based on surgical location: extradural, intradural extramedullary, and intramedullary procedures. Differences between groups were tested with the Fisher exact test.ResultsThe number of neurological complications was significantly lower in the intramedullary procedure group with NIOM. There was no significant difference in the number of complications in patients undergoing intra- or extradural extramedullary procedures with versus without NIOM.ConclusionsNIOM decreases the risk of neurological complications in spinal cord surgery, but not in extramedullary spinal canal procedures.     

甲基强的松龙对大鼠急性脊髓损伤截瘫后肠道细菌移位的抑制作用

背景：我们以往的研究显示急性脊髓损伤截瘫后,自主神经紊乱导致的肠道动力障碍促使细菌移位的发生。目前认为大剂量甲基强的松龙可促进脊髓损伤患者神经功能的恢复。但不清楚甲基强的松龙能否通过促进神经功能的恢复,从而抑制急性脊髓损伤后肠道细菌的移位？本实验的目的为明确上述问题。方法：建立大鼠脊髓损伤截瘫模型。实验组大鼠脊髓损伤截瘫后立即给予大剂量甲基强的松龙,对照组大鼠脊髓损伤截瘫后立即给予生理盐水作为对照,在急性脊髓损伤后24、72小时及1周评估BBB运动功能得分,采血行细菌培养和内毒素检测。同时采集肠系膜淋巴结、脾脏、肝脏标本行细菌培养。脊髓损伤后1周行肠系膜淋巴结、脾脏、肝脏、空肠和回肠组织学观察。结果：急性脊髓损伤后1周,实验组大鼠BBB运动得分显著高于对照组(10.36±0.86 vs 6.32±1.02, P <0.05)。两组动物在脊髓损伤后24小时均发现内毒素血症及细菌生长。然而,脊髓损伤后72小时及1周,实验组大鼠血浆内毒素水平显著低于对照组(损伤后72小时：216.15±12.90 vs 435.54±10.76 , P <0.05,损伤后1周：106.58±18.56 vs 368.85±17.35, P <0.05)。脊髓损伤截瘫后移位细菌主要为大肠杆菌、阴沟杆菌、大肠埃希氏菌、普通变形杆菌、肠粪球菌等。脊髓损伤后1周实验组大鼠肠系膜淋巴结、脾脏、肝脏、空肠和回肠组织学变化程度较对照组轻。结论：大剂量甲基强的松龙冲击疗法可抑制急性脊髓损伤后肠道细菌的移位。急性脊髓损伤患者立即给予甲基强的松龙和抗生素可能有助于抑制潜在的细菌移位。     

MK-801在脊髓缺血中的神经保护作用

目的地佐环平(MK-801)对脊髓缺血中神经保护作用的研究。方法建立新西兰兔脊髓缺血模型,利用HE染色、原位末端转移酶标记技术(TUNEL)、免疫组化、逆转录反应系统(RT-PCR)等技术检测N-甲基-D-天门冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)、诱导型一氧化氮合酶(inducible Nitric Oxide Synthase,iNOS)、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)的表达水平,观察不同剂量MK-801在脊髓缺血中的神经保护作用。结果对照组脊髓结构完全消失,低剂量组结构较完整,高剂量组缺血损害程度最轻,假手术组脊髓结构正常。NMDAR、iNOS、Caspase-3等蛋白在神经元中有明确表达。凋亡指数、NMDAR、iNOS、Caspase-3 mRNA表达水平在对照组最高,低剂量组、高剂量组,假手术组则逐渐降低,差别具有统计学意义(P<0.05)。结论 MK-801能抑制神经细胞凋亡,对脊髓缺血具有神经保护作用。     

Methylprednisolone and tetrandrine in combination with direct current electrical field for treating acute spinal cord injury

BACKGROUND: The direct current electrical field can effectively promote the regeneration of the spinal cord; moreover, methylprednisolone (MP) can relieve secondary edema after spinal cord injury. Tetrandrine (Tet) is an effective component of hanfangji and can protect the effect of spinal cord and axis-cylinder. Whether direct current electrical field combining with MP or Tet has synergic or strengthening effect on treating complete spinal cord injury or not should be studied further. OBJECTIVE:To study the effect of direct current electrical field assisted by MP and Tet on treating spinal cord injury. DESIGN: Randomized controlled animal study. SETTING: People's Hospital of Hainan Province. MATERIALS: A total of 45 healthy hybrid dogs, of both genders, weighing 10–12 kg, aged 1.5–2 years, were provided by Animal Center of Hainan Province. Somatosensory evoked potential meter (DANTEC Company), IBAS-2.0 imaging analysis meter (Germany), and self-made electronic stimulator. METHODS: The experiment was carried out in Hainan People's Hospital from May 2001 to June 2004. All experimental dogs were randomly divided into 4 groups: control group (n =9), electrostimulating group (n =12), MP + electrostimulating group (n =12) and Tet + electrostimulating group (n =12). ① After anesthesia, Allen WD method was used to induce complete spinal cord injury. The metal bar, which was 10 cm in height fell freely and vertically hit the spinal cord to provide a complete spinal cord injury. Dogs in control group and electrostimulating group were implanted electrical stimulators 6 hours after spinal cord injury (no electricity in control group); dogs in MP + electrostimulating group were injected 30 mg/kg MP for 15 minutes at 2 hours after spinal cord injury and electrical stimulators implanted at 6 hours after injury; dogs in Tet + electrostimulating group were intravenously injected with 7.5 mg/kg Tet at 2 hours after spinal cord injury and electrical stimulators implanted at 6 hours after injury; and then, 7.5 mg/kg Tet injected at days 2 and 3 after injury. ② Specimens were taken from control group from three dogs of every month; from the injured segments of spinal cords at 1 month, 2 months and 3 months; and from electrostimulating group, MP + electrostimulating group and Tet + electrostimulating group of 4 dogs for histological examinations. ③ Detection of neurological function: Neurological function was evaluated with the functional 10 grading system. The scores ranged from 0 to 10 (0: complete paraplegia; 10: normality). ④ Detection of cortical somatosensory evoked potential (CSEP): According to the scheme formulated by the International Electroencephalographical Association, the patterns of the fundamental waves were P1–N1–P1 waves. The latency of the P1 wave and the amplitude of P1–N1 waves were mainly observed individually at 1, 2 and 3 months after the injury. ⑤ Histological detection: All spinal cord specimens of the injuried segment were harvested at 1, 2 and 3 months after injury. They were stained with hematoxylin and Nissl staining methods, and then were observed under an optical microscope, and the neurons were counted. The sectional areas of the neurons and the density of the Nissl bodies were measured by a system image pattern analysis (IBAS-2.0, Germany). MAIN OUTCOME MEASURES: The neurological function, cortical somatosensory evoked potential, neuronal amount, sectional area of neurons and Nissl body density at 1 to 3 months after injury. RESULTS: All 45 experimental dogs were involved in the final analysis. ① Detection of neurological function: One month later, the dogs in MP + electrostimulating group could walk, but the dogs in electrostimulating group and Tet + electrostimulating group could stand. Two months after injury, the dogs in MP + electrostimulating group almost recovered to normal, but the dogs in electrostimulating group could walk and those in Tet + electrostimulating group could run. Those in control group had no parent recovery. ② Detection of P1 latency and P1–N1 amplitude: Changes of P1 latency in control group were long and P1–N1 amplitude was very low at 1 month later. Compared to electrostimulating group, MP + electrostimulating group and Tet + electrostimulating group, there were significant differences (P < 0.05). P1 latency was manifestly shortened and amplitude were raised in electrostimulating group, MP + electrostimulating group and Tet + electrostimulating group. Those in MP + electrostimulating group and Tet + electrostimulating group were superior to those in electrostimulating group and there were significant differences (P < 0.05). ③ Sectional areas of neurons and Nissl body density: At 1–3 months after injury, sectional areas of neurons were larger in electrostimulating group [(170.14±7.45), (209.60±14.80), (312.47±12.63) μm2], MP + electrostimulating group [(282.18±15.25), (418.18±16.27), (515.25±15.10) μm2] and Tet + electrostimulating group [(231.81±7.38), (322.67±8.45), (386.82±10.42) μm2] than control group[(98.12±4.93), (113.50±6.74), (122.59±8.03) μm2, P < 0.05]; especially, sectional area was the largest in MP + electrostimulating group. At 1–3 months after injury, Nissl body density was more in electrostimulating group (170.14±7.45, 209.60±14.80, 312.47±12.63), MP + electrostimulating group (282.18±15.25, 418.18±16.27, 515.25±15.10) and Tet + electrostimulating group (231.81±7.38, 322.67±8.45, 386.82±10.42) than control group (98.12±4.93, 113.50±6.74, 122.59±8.03, P < 0.05); especially, Nissl body density was the most in MP + electrostimulating group. CONCLUSION: The direct current electrical field can effectively promote spinal cord regeneration. The combination of direct current electrical field with large dose MP or Tet has synergistic effects for treating spinal cord injury. The curative effects of direct current electrical field with large dose MP are much better than those with Tet.     

The neuroprotective effect of treatment of valproic Acid in acute spinal cord injury

Objective

Valproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model.

Methods

Locomotor function was assessed according to the Basso-Beattie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation.

Results

Basso-Beattie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05).

Conclusion

VPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.     

Correlation of injury severity and tissue Evans blue content, lipid peroxidation and clinical evaluation in acute spinal cord injury in rats

OBJECTIVE: To demonstrate the changes in microvascular permeability occurring in association with graded acute spinal cord injury and to determine whether tissue Evans blue content is a useful indicator of the severity of spinal cord injury. The study also aimed to test the ability of the Evans blue method to demonstrate secondary injury after spinal cord contusion. METHODS: In step one of the study, spinal cord lipid peroxidation levels and spinal cord Evans blue content were evaluated at 2 h post-injury in five groups of rats: a control group, a laminectomy-only group and three trauma groups (10, 50, and 100 gcm). In step two, these rats were used for Evans blue assessment following clinical examination at 24 h post-injury. RESULTS: The laminectomy-only group showed no difference from the control group with regard to spinal cord lipid peroxidation levels, tissue Evans blue content, and clinical findings. Increase in spinal cord tissue Evans blue content and lipid peroxidation was correlated with increasing intensity of trauma. There was a negative correlation between trauma intensity and clinical findings, and there was an increase in spinal cord tissue Evans blue content at 24 h compared with that at 2 h. CONCLUSIONS: Determination of spinal cord tissue Evans blue content is a reliable, rapid, simple and inexpensive method that can be used in experimental spinal cord injury to assess the severity of injury and to evaluate neuroprotection studies. The present study is the first to show that the Evans blue technique is a useful method to demonstrate secondary injury of spinal cord tissue and vasculature.     

人参皂甙对损伤脊髓诱发电位的影响

目的　研究猫急性脊髓损伤 (SCI)后脊髓诱发电位 (SCEP)的变化规律及人参皂甙 (GS)对其的影响 ,探讨 GS对 SCI的作用 ,旨在寻求治疗 SCI的新方法。方法　采用改良 Allen氏重量打击法制作猫急性脊髓损伤模型 ,动物随机分组 ,通过电生理及病理学方法 ,研究 SCEP的变化规律及 GS对其的影响 ,脊髓形态学的改变作为进一步的佐证。结果　 (1)损伤组伤后 SCEP辐值随时间延长逐渐变小 ,潜伏期逐渐延长 ;治疗组波形则逐渐恢复 ,6 h全部恢复 ,差异显著。(2 )光镜下两组均有水肿、中心性出血 ,神经元空泡变性 ,核溶解或固缩 ,尼氏小体消失 ,部分神经纤维脱髓鞘或断裂 ,损伤组最重 ,治疗组均有不同程度的恢复。结论　 GS对 SCI有治疗作用。     

Effect of methylprednisolone on motor function and spinal cord blood flow after spinal cord compression in rats

The effect of methylprednisolone (MP) on neurologic recovery and spinal cord blood flow (SCBF) was investigated up to 4 days after a spinal cord compression injury in rats. The injury was produced at midthoracic level by applying a load of 35 g on a 2.2 x 5.0 mm compression plate for 5 min, which resulted in transient paraparesis. MP was given as a bolus dose of 30 mg/kg i.v. 60 min after injury (n = 20) and controls were given saline (n = 10). The motor performance was assessed daily as the capacity angle on the inclined plane and SCBF was measured by 14C-iodoantipyrine autoradiography on Days 1 or 4. On Day 1 the capacity angle was reduced from about 63 degrees preoperatively to 33 +/- 2 degrees (mean +/- SEM) in the control group and to 50 +/- 1 degrees in the group treated with MP (p less than 0.05). Thereafter there was a slight improvement in both groups, but the difference persisted throughout the observation period. On Day 4 both gray and white matter SCBF was better preserved in MP-treated animals than in the control group (59 +/- 4 versus 49 +/- 3 ml/min/100 g tissue for gray matter and 13.6 +/- 0.6 versus 10.7 +/- 0.8 ml/min/100 g tissue for white matter). Posttraumatic treatment with MP, thus, improved both the neurologic recovery during the first 4 days and SCBF as measured on Day 4. It is speculated that the effect of MP is at least partly exerted on the vascular bed.     

丹酚酸B促进大鼠急性脊髓损伤修复及量效关系探讨

目的 研究腹腔注射丹酚酸B(Sal B)对大鼠急性脊髓损伤(SCI)模型的神经保护作用和促功能恢复作用,探讨Sal B在急性SCI治疗的应用价值,并探讨其量效关系. 方法参照Allen法制作SD大鼠T9脊髓节段急性损伤模型,腹腔注射Sal B或PBS液,按照注射液的不同分为4组:Sal B高剂量组(20 mg/kg组),Sal B中剂量组(10 mg/kg组),Sal B低剂量组(2 mg/kg组)和对照组(注射PBS液),每组12只.用比色法检测髓过氧化物酶活性;用免疫组织化学染色法检测损伤脊髓节段MMP-1、c-Fos抗体表达情况,用干湿重法评价的水肿程度,并采用后肢功能评分(BBB)评分评价10 d内大鼠的运动功能恢复情况. 结果损伤后4 h Sal B治疗组髓过氧化物酶活性下降,损伤后1 dHE染色切片显示SalB组治疗后局部组织损伤减轻,炎性细胞浸润数量减少,损伤后1d免疫组化染色结果显示,Sal B治疗组比对照组MMP-1表达减少,c-Fos表达下调;Sal B治疗组水肿程度轻于对照组,从SCI后第7天起,SalB组高剂量组(20 mg/kg组)和对照组之间的BBB评分有显著性差异(P<0.05).各指标改善情况与Sal B剂量呈正相关性. 结论 Sal B可减轻大鼠SCI后的组织损伤,下调损伤相关因子MMP-1和c-Fos的表达,降低损伤局部髓过氧化物酶活性,减轻组织水肿,并能促进损伤大鼠的功能恢复.     

Poly-lactic acid and agarose gelatin play an active role in the recovery of spinal cord injury

Objective To investigate the role of poly-lactic acid and agarose gelatin in promoting the functional recovery of the injured spinal cord. Methods Poly-lactic acid ( PLA) or agarose was embedded in the space between two stumps of the hemisectioned spinal cord. Immunohistochemistry was used to show astroglia proliferation and the infiltration of RhoA-positive cells. Locomotor activity recovery was evaluated by testing the function of hindlimbs. Results Astrogli-as and RhoA labeled non-neuronal cells accumulated in the area adjacent to the implant, while the number of RhoA-positive cells was decreased dramatically in the absence of implant. Animals implanted with agarose gelatin recovered more quickly than those with PLA, concomitant with a higher survival rate of the neurons. Conclusion Both PLA and agarose gelatin benefited the recovery of spinal cord after injury by providing a scaffold for astroglia processes. Modulation of the rigidity, pore size and inner structure of PLA and agarose gelatin might make these biodegradable materials more effective in the regeneration of the central nervous system (CNS).     

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury

After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI.     

丹酚酸B促进大鼠急性脊髓损伤修复及量效关系探讨

目的 研究腹腔注射丹酚酸B(Sal B)对大鼠急性脊髓损伤(SCI)模型的神经保护作用和促功能恢复作用,探讨Sal B在急性SCI治疗的应用价值,并探讨其量效关系. 方法参照Allen法制作SD大鼠T9脊髓节段急性损伤模型,腹腔注射Sal B或PBS液,按照注射液的不同分为4组:Sal B高剂量组(20 mg/kg组),Sal B中剂量组(10 mg/kg组),Sal B低剂量组(2 mg/kg组)和对照组(注射PBS液),每组12只.用比色法检测髓过氧化物酶活性;用免疫组织化学染色法检测损伤脊髓节段MMP-1、c-Fos抗体表达情况,用干湿重法评价的水肿程度,并采用后肢功能评分(BBB)评分评价10 d内大鼠的运动功能恢复情况. 结果损伤后4 h Sal B治疗组髓过氧化物酶活性下降,损伤后1 dHE染色切片显示SalB组治疗后局部组织损伤减轻,炎性细胞浸润数量减少,损伤后1d免疫组化染色结果显示,Sal B治疗组比对照组MMP-1表达减少,c-Fos表达下调;Sal B治疗组水肿程度轻于对照组,从SCI后第7天起,SalB组高剂量组(20 mg/kg组)和对照组之间的BBB评分有显著性差异(P<0.05).各指标改善情况与Sal B剂量呈正相关性. 结论 Sal B可减轻大鼠SCI后的组织损伤,下调损伤相关因子MMP-1和c-Fos的表达,降低损伤局部髓过氧化物酶活性,减轻组织水肿,并能促进损伤大鼠的功能恢复.     

Poly-lactic acid and agarose gelatin play an active role in the recovery of spinal cord injury

Objective To investigate the role of poly-lactic acid and agarose gelatin in promoting the functional recovery of the injured spinal cord. Methods Poly-lactic acid （PLA） or agarose was embedded in the space between two stumps of the hemisectioned spinal cord. Immunohistochemistry was used to show astroglia proliferation and the infiltration of RhoA-positive cells. Locomotor activity recovery was evaluated by testing the function of hindlimbs. Results Astroglias and RhoA labeled non-neuronal cells accumulated in the area adjacent to the implant, while the number of RhoA-posirive cells was decreased dramatically in the absence of implant. Animals implanted with agarose gelatin recovered more quickly than those with PLA, concomitant with a higher survival rate of the neurons. Conclusion Both PLA and agarose gelatin benefited the recovery of spinal cord after injury by providing a scaffold for astroglia processes. Modulation of the rigidity, pore size and inner structure of PLA and agarose gelatin might make these biodegradable materials more effective in the regeneration of the central nervous system （CNS）.     

甲基强的松龙对急性脊髓损伤神经元保护作用的实验研究

目的探讨甲基强的松龙对急性脊髓损伤(ASCI)后神经元是否具有保护作用。方法大鼠随机分为2组，即模型组和正常对照组(N组)，模型组建立脊髓半横断损伤模型后又分两组，即激素治疗组(M组)，腹腔注射甲基强的松龙(MP)；模型对照组(B组)术后不做处理。每组大鼠观察损伤后3d、7d、15d和30d。取脊髓损伤部位标本做光镜病理组织学检查，观察正常神经元和变性神经元的数量变化。结果(1)B组在ASCI早期脊髓损伤区的灰白质被明显的破坏，有出血及坏死，可见多量空泡状细胞和溃变的神经纤维，部分组织液化。在损伤灶内见正常神经元及神经纤维的数量稀少，多数神经元呈现不同程度的变性乃至坏死。随着时间的延长，神经元数量进一步减少，胶质细胞增生形成疤痕，或者液化形成囊腔。病变常常累及对侧组织，而M组的脊髓损伤区组织结构的变化与B组基本相同。(2)在ASCI后3d，M组的正常神经元数量少于B组，变性神经元数量与B组相近；在损伤7d以后，随着时间的延长，B组的变性神经元数量减少的同时，正常神经元的数量稍有减少，而M组的变性神经元数量减少的同时，正常神经元数量有所增加。结论(1)MP对ASCI后的继发性组织结构破坏无明显的改善作用；(2)MP在ASCI早期能促使神经元的死亡，但在后期能增加正常神经元的数量，其机理有待于进一步研究。     

Results of neuromodulation for the management of chronic pain

Background and purpose : Neuromodulative treatment of chronic pain syndromes is a modern mode of treatment of neuropathic and ischaemic pain. Its effectiveness is well documented in the literature. The objective of this work is to present the results of treatment of chronic pain syndromes on the basis of eight-year experience in our department. Material and methods : Since 2002, we have conducted 9 operations of motor cortex stimulation (MCS), 2 of deep brain stimulation (DBS), 45 of spinal cord stimulation (SCS) and 5 of sacral root stimulation (SRS) in the treatment of chronic pain. Results : We obtained good long-term results of neuromodulation in the form of clinical improvement (> 50%) in 4 of 9 patients with MCS (44%), in 13 diagnosed with failed back surgery syndrome (FBSS), 8 with other neuropathic pain, and 11 with angina pectoris from a group of 45 treated with SCS. Sacral root stimulation has been successful in 3 of 5 patients with perianal pain. The best treatment results in SCS, although not statistically significant, were observed in patients treated due to FBSS (13 out of 15) and angina pectoris (11 out of 15) (p = 0.12). In patients with neuropathic pain, peripheral and central, improvement was obtained in 8 out of 15 patients. Conclusions : A good indication for spinal cord stimulation is FBSS and angina pectoris. Motor cortex stimulation is helpful in the treatment of chronic central neuropathic pain. Further observations and a larger group of patients are necessary for a reliable assessment of the effectiveness of neuromodulative treatment of chronic pain in our clinic.     

FK 506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat

We examined the efficacy of FK 506 in reducing tissue damage after spinal cord injury in comparison to methylprednisolone (MP) treatment. Rats were subjected to a photochemical injury (T8) and were given a bolus of MP (30 mg/kg), FK 506 (2 mg/kg), or saline. An additional group received an initial bolus of FK 506 (2 mg/kg) followed by daily injections (0.2 mg/kg intraperitoneally). Functional recovery was evaluated using open-field walking, inclined plane tests, motor evoked potentials (MEPs), and the H-reflex response during 14 days postoperation (dpo). Tissue sparing and glial fibrillary acidic protein (GFAP), biotinylated tomato lectin LEC, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1 beta) immunoreactivity were quantified in the injured spinal cord. FK 506-treated animals demonstrated significantly better neurologic outcome, higher MEP amplitudes, and lower H-wave amplitude compared to that of saline-treated rats. In contrast, administration of MP did not result in significant differences with respect to the saline-treated group. Histologic examination revealed that tissue sparing was largest in FK 506-treated compared to saline and MP-treated animals. GFAP and COX-2 reactivity was decreased in animals treated with FK 506 compared to that in animals given MP or saline, whereas IL-1 beta expression was similarly reduced in both FK 506- and MP-treated groups. Microglia/macrophage response was reduced in FK 506 and MP-injected animals at 3 dpo, but only in MP-treated animals at 7 dpo with respect to saline-injected rats. Repeated administrations of FK 506 improved functional and histologic results to a greater degree than did a single bolus of FK 506. The results indicate that FK 506 administration protects the damaged spinal cord and should be considered as potential therapy for treating spinal cord injuries.     

Early methylprednisolone impact treatment for sensory and motor function recovery in patients with acute spinal cord injury A self-control study

BACKGROUND: For the treatment of spinal cord injury, any pathological changes of the injured tissue should be primarily corrected or reversed. Any remaining fibrous function and neurons with intact structure should be retained, and the toxic substances caused by ischemia-hypoxia following spinal cord injury, should be eliminated to create a favorable environment that would promote neural functional recovery. OBJECTIVE: This study was designed to investigate the effects of the impact of early methylprednisolone-treatment on the sensory and motor function recovery in patients with acute spinal cord injury. DESIGN: A self-control observation. SETTING: Department of Spine Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. PARTICIPANTS: Forty-three patients with acute spinal cord injury were admitted to the Department of Spine Surgery, First Affiliated Hospital of Nanjing Medical University, between October 2005 and September 2007. These patients were recruited for the present study. The patients comprised 33 males and 10 females, and all met with the inclusive criteria namely, the time between suffering from acute spinal cord injury and receiving treatment was less than or equal to eight hours. METHODS: According to the protocol determined by the State Second Conference of Acute Spinal Cord Injury of USA, all patients received the drop-wise administration of a 30-mg/kg dose of methylprednisolone (H200040339,500mg/bottle, Pharmacia N.V/S.A, Belgium) for 15 minutes within 8 hours post injury. After a 45-minute interval, methylprednisolone was administered at 5.4mg/kg/h for 23 hours. MAIN OUTCOME MEASURES: Prior to and post treatment, acupuncture sense and light touch scoring were performed at 28 dermatomic area key points, including occipital tuberosity and supraclavicular fossa. At the same time, motor scoring of key muscles among 10 pairs of sarcomeres was also performed.RESULTS: All 43 patients participated in the final analysis. There was no significant difference of sensory and motor scores in patients with complete acute spinal cord injury between prior to and post methylprednisolone impact treatment (P>0.05). The motor score was significantly decreased in patients with incomplete acute spinal cord injury post methylprednisolone impact treatment (P<0.01).CONCLUSION: Early methylprednisolone impact may improve the motor function of patients with incomplete acute spinal cord injury. However, it has no influences on patients with complete acute spinal cord injury.