Methylene blue decreases ischemia-reperfusion (I/R)-induced spinal cord injury: an in vivo study in an I/R rabbit model

OBJECTIVES: To evaluate the effects of intravenous methylene blue (MB) administration on ischemia-reperfusion (I/R) injury of the spinal cord (SC). METHODS: 16 rabbits were randomly assigned either to group M (n = 8; receiving MB, intervention group) or group C (n = 8; control group) and underwent a 30-min period of SC ischemia by clamping the abdominal aorta between the left renal artery and the aortic bifurcation. 15 min before clamping, rabbits received either intravenous MB (10 mg/kg; group M) or normal saline (group C). The two groups were compared 24 h postoperatively both histologically and for neurological function, using a Tarlov score. Measurements to determine levels of malondialdehyde (MDA) and glutathione (GSH) in the SC tissue were also performed. RESULTS: Neurological impairment and spinal tissue MDA levels were significantly lower in animals treated with MB (p < 0.001). In contrast, spinal GSH levels were significantly higher in group M (p < 0.001). Histological examination revealed that the integrity of the SC was better preserved in the MB group, whereas cords from the control group exhibited evidence of acute neuronal injury. CONCLUSIONS: The prophylactic use of MB reduces neurological injury and improves clinical outcomes in the rabbit SC I/R model. These effects are probably mediated by the drug's antioxidant properties.     

氢饱和生理盐水对兔脊髓缺血再灌注损伤的神经保护作用

目的 研究氢气对脊髓缺血再灌注损伤的保护作用及其潜在机制。方法 新西兰兔随机分为3组：对照组、脊髓缺血再灌注损伤组和氢水治疗组。对照组仅接受暴露,无脊髓缺血再灌注损伤;缺血再灌注组动物采用ZIVIN法建立脊髓缺血再灌注损伤模型,造成脊髓腰骶段缺血35 min 后行再灌注;氢水治疗组动物在再灌注前5 min腹腔注射饱和氢盐水（5 mL/kg）,再灌注后8 h重复注射。不同时间点检测后肢运动功能。术后72 h取脊髓进行HE染色、TUNEL染色、氧化-抗氧化指标检测及ELISA检测细胞因子。结果 含氢生理盐水治疗能显著改善动物神经功能、抑制脊髓神经元凋亡、抑制氧化应激、改善抗氧化能力,同时降低炎症相关细胞因子,从而发挥脊髓保护作用。结论 腹腔注射含氢生理盐水通过抗氧化和抗炎对脊髓缺血再灌注损伤发挥保护作用。     

The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia-reperfusion injury in rabbits: experimental study

STUDY DESIGN: Experimental study.Objectives: To determine the neuroprotective effects of zinc and melatonin on spinal cord ischemia-reperfusion (I/R) injuries of rabbits.Setting: The Experimental Research Centre of Sel?uk University, Konya, Turkey. METHODS: Twenty-four male rabbits underwent spinal cord ischemia by clamping the thoraco-abdominal aorta for 20 min. Twenty minutes before the aortic clamping, animals received zinc, melatonin or a combination of both. Neurological examination of the animals was performed three times during reperfusion period. The animals were killed 24 h after reperfusion. Spinal cord samples were taken for biochemical and histopathological evaluation. RESULTS: Pre-treated animals with zinc, melatonin or combination displayed better neurological outcomes than the I/R group (P<0.05). Zinc, melatonin and combined treatment prevented spinal cord injury by reducing apoptosis rate (P<0.05) and preserving intact ganglion cell numbers (P<0.05). Zinc pre-treatment protected spinal cord by preventing malondialdehyde (MDA) formation (P=0.002), increasing glutathione peroxidase (GPx) activity (P=0.002) and decreasing xanthine oxidase enzyme activity (P=0.026) at molecular level. Melatonin treatment also resulted with MDA formation (P=0.002), increased GPx activity (P=0.002) and decreased xanthine oxidase activity (P=0.026). CONCLUSION: The results of the study showed that prophylactic zinc and melatonin use in spinal cord I/R not only suppressed lipid peroxidation by activating antioxidant systems but also had significant neuroprotective effects by specifically improving the neurological and histopathological situation.     

Protective effect of ketamine on ischemic spinal cord injury in rabbits

We tested our hypothesis that a commonly used anesthetic, ketamine, may offer benefits to protect animals from spinal cord injury, using the ischemia/reperfusion (I/R) injury rabbit model in a randomized controlled study. We used 24 white adult Japanese rabbits from the animal facility at the Medical College of Wuhan University. The rabbits were randomly assigned to one of three groups, eight rabbits per group: group I, sham-operation group; group II, I/R group; group III, I/R with ketamine treatment group. Spinal cord ischemia was induced by infrarenal aortic cross-clamp for 45 min in group II and group III, and ketamine was intravenously infused at 10 mg/kg in 15 mL 0.9% sodium chloride at a speed of 1.5 mL/min to animals in group III, once at 10 min before aortic clamping and once at the onset of reperfusion. Postoperative neurological function, electromyography of rear limbs, histopathology, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity in the spinal cord were assessed in all animals. Compared with the control group I, group II showed significant I/R injury-induced changes in neurological function scores, histopathology, and electromyography (p < 0.01). However, group III with ketamine treatment significantly reversed the changes in all these parameters (p < 0.01). At the same time, the I/R-induced increase in MDA content observed in group II was also significantly reduced in group III (p < 0.01), and the I/R-induced decreases in SOD activity were also significantly prevented in group III (p < 0.01). After ketamine treatment, all parameters examined in group III were not significantly different from those obtained in group I. Ketamine showed potent protective effects against spinal cord I/R injury in the rabbit model and protected loss of antioxidant activity in spinal cord tissues.     

不同高压氧预处理方案对兔脊髓缺血再灌注损伤的影响

目的 探讨不同高压氧预处理方案对兔脊髓缺血再灌注损伤的影响.方法 新西兰大白兔45只,月龄4～5月,体重2.0～2.5 kg,随机分为5组:假手术组(S组,n=5)开腹剥离左肾动脉下段腹主动脉但不阻断血流,20 min后关腹;脊髓缺血再灌注组(IR组,n=10)采用左肾动脉下段腹主动脉阻断法建立脊髓缺血再灌注损伤模型,缺血20 min后恢复灌注;不同方案高压氧预处理组(H_(1～3)组,n=10)分别接受连续5 d(H_1组)、10 d(H_2组)或20 d(H_3组)高压氧预处理(2.5 ATA,吸入氧浓度100%),1h/d,末次高压氧预处理结束后24 h时,建立脊髓缺血再灌注模型.再灌注48 h时,采用修正Tarlov评分,评价后肢运动功能.然后取L_5脊髓节段,分别行HE、TUNEL和nuoro-Jade B染色,计数脊髓正常神经元、凋亡神经元和变性神经元.结果 与S组比较,IR组后肢运动功能评分和脊髓前角正常神经元计数降低(P<0.01);与IR组比较,H_1组和H_2组后肢运动功能评分和脊髓前角正常神经元计数升高,凋亡神经元计数和变性神经元计数降低(JP<0.01),H_3组各指标差异无统计学意义(P>0.05);H_1组和h_2组各指标比较差异无统计学意义(P>0.05);与H_1组和H_2组比较,H_3组后肢运动功能评分和脊髓前角正常神经元计数降低,凋亡神经元计数和变性神经元计数升高(P<0.01).结论 连续5 d或10 d高压氧预处理(2.5 ATA,吸入氧浓度100%)可减轻脊髓缺血再灌注损伤;而连续20 d高压氧预处理无神经保护作用.     

ATP-MgCl2 utilization for spinal cord protection during experimental thoracic aortic occlusion.

BACKGROUND: In this experimental study we investigate the effect of intravenous ATP-MgCl**2 administration for prevention of spinal cord injury occurring due to ischemia induced by aortic cross clamping. METHODS: Ten rabbits were studied. The abdominal aorta is ligated below the left renal artery. Five rabbits served as a control group and received no medication during 30 minutes of ischemic period. The other 5 rabbits received during 30 minutes of aortic occlusion ATP-MgCl2 solution (100 micromol/ml for each). Distal and proximal aortic pressures are measured during the procedure and incisions are closed. Rabbits are observed for 24 hours for their neurological status and scored accordingly. Specimens from the spinal cord are taken for electron microscopic investigations. RESULTS: All of the control group rabbits were paraplegic. One of the ATP-MgCl2 group rabbits was paraparesic and the others were normal Distal aortic pressure was 9+/-3 mmHg for the control group and was 17+/-4 mmHg for the ATP-MgCl2 group (p<0.05). Electron microscopic studies showed the preserved ultrastructure for ATP-MgCl2 group. CONCLUSIONS: ATP-MgCl2 administration during spinal cord ischemia reduces spinal cord injury. This may be an alternative modality for the protection of the spinal cord during aortic surgery.     

辛伐他汀预先给药对大鼠脊髓缺血再灌注损伤的影响

目的 评价辛伐他汀预先给药对大鼠脊髓缺血再灌注损伤的影响.方法 雄性SD大鼠96只,体重220～280 g,随机分为3组(n=32):假手术组(S组)、缺血再灌注组(IR组)和辛伐他汀预先给药组(Si组).IR组和Si组采用夹闭腹主动脉45 min后开放的方法制备脊髓缺血再灌注模型,Si组制备模型前3 d开始以辛伐他汀20 mg·kg-1·d-1灌胃,连续3 d.分别于再灌注6、12、24 h时取8只大鼠,进行后肢运动功能评分.分别于再灌注2、6、12、24 h时取8只大鼠,采集静脉血样,测定血清脑型肌酸激酶同工酶(CK-BB)活性.取完血样后取大鼠脊髓组织,测定Toll样受体4(TLR4)mRNA表达、NF-κB活性、TNF-α含量和细胞间粘附分子-1(ICAM-1)含量,光镜下观察脊髓的病理学结果.结果 与S组比较,IR组和Si组后肢运动功能评分降低,血清CK-BB活性、脊髓TLR4mRNA表达、NF-κB活性、TNF-α和ICAM-1含量升高(P＜0.05或0.01).与IR组比较,Si组后肢运动功能评分升高,血清CK-BB活性、脊髓TLR4 mRNA表达、NF-κB活性、TNF-α和ICAM-1含量降低(P＜0.05或0.01).Si组脊髓病理学损伤程度轻于IR组.结论 辛伐他汀预先给药可减轻大鼠脊髓缺血再灌注损伤,其机制与下调TLR4表达、抑制NF-κB激活,从而减轻炎性反应有关.     

Neuroprotective effect of regional carnitine on spinal cord ischemia--reperfusion injury.

OBJECTIVE: The purpose of this study was to investigate the effect of regional infusion of carnitine on spinal cord ischemia--reperfusion (I--R) in rabbits. METHODS: The 36 rabbits were divided into four equal groups, group I (sham operated, no I--R injury), group II (control, only I--R), group III (I--R+intraaortic lactated Ringer's, LR, during aortic occlusion), group IV (I--R+LR plus 100mg/kg carnitine). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. The spinal cord function of all animals was assessed clinically 24h after aortic declamping. Spinal cord samples were taken to measure the levels of tissue malondialdehyde (MDA) and to evaluate the histopathological changes. RESULTS: We found significant increases in the levels of MDA in groups II and III compared with group I (P<0.01), and elevation of MDA in group IV was insignificant. In group II, all animals (100%) were paraplegic with Tarlov's score of 0 and in group III, eight animals (88%) were paraplegic with Tarlov's score of 0 or 1. None of the animals (0%) from group IV was paraplegic. Histologic examination of spinal cords from group IV animals revealed that the appearance of the spinal cord was relatively preserved, whereas spinal cords from groups II and III had evidence of acute neuronal injury. CONCLUSION: The results suggest that regional infusion of carnitine during aortic clamping reduces spinal cord injury and prevents neurologic damage in rabbit spinal cord I--R model.     

Adenosine A2A agonist reduces paralysis after spinal cord ischemia: correlation with A2A receptor expression on motor neurons

BACKGROUND: The adenosine A2A agonist ATL-146e ameliorates reperfusion inflammation, reducing subsequent paralysis and neuronal apoptosis after spinal cord ischemia. We hypothesized that neuroprotection with ATL-146e involves inducible neuronal adenosine A2A receptors (A2A-R) that are upregulated after ischemia. METHODS: Eighteen rabbits underwent laparotomy, and 14 sustained spinal cord ischemia from cross-clamping the infrarenal aorta for 45 minutes. One group (ischemia-reperfusion [I/R] + ATL) received ATL-146e intravenously for 3 hours during spinal cord reperfusion. A second group (I/R) received equivolume intravenous saline solution for 3 hours and served as an ischemic control, and a third group (Sham) underwent sham laparotomy. At 48 hours, all subjects were assessed for motor impairment using the Tarlov scoring system (0 to 5). Lumbar spinal cord sections were immunolabeled for A2A-R and graded in a blinded fashion using light microscopy. RESULTS: There was a significant improvement in Tarlov scores in I/R + ATL animals compared with the I/R group. Sham-operated animals demonstrated no A2A-R immunoreactivity. There was a dramatic increase in A2A-R immunoreactivity in neurons of lumbar spinal cord sections from I/R compared with I/R + ATL and sham-operated animals. CONCLUSIONS: Reduction in paralysis in animals receiving ATL-146e correlates with the new finding of A2A-R expression on lumbar spinal cord motor neurons after ischemia. Adenosine A2A agonists may exert neuroprotective effects by binding to inducible neuronal A2A-R that are upregulated during spinal cord reperfusion, and reduced in response to administration of an A2A-R-specific agonist.     

控制性低压灌注对兔脊髓缺血再灌注时磷酸化Akt和磷酸化ERK表达的影响

目的 探讨控制性低压灌注对兔脊髓缺血再灌注时磷酸化蛋白质丝氨酸苏氨酸激酶(p-Akt)和磷酸化细胞外信号调节激酶1/2 (p-ERK1/2)表达的影响.方法 雄性日本大耳白兔36只,3月龄,体重2.0 ～ 2.5 kg,采用随机数字表法,将其随机分为3组(n＝12):假手术组(S组)、脊髓缺血再灌注组(I/R组)和控制性低压灌注组(LP组).I/R组和LP组采用在肾动脉下水平阻断腹主动脉25min行再灌注的方法制备脊髓缺血再灌注损伤模型.LP组再灌注10 min期间维持腹主动脉远端血压45～55 mm Hg.分别于再灌注1、3、7、28 d时进行后肢运动功能功能.每组于再灌注1d时处死动物,取脊髓组织,测定p-Akt、p-ERK1/2表达及神经元凋亡情况,计算凋亡指数,电镜下观察病理学结果.结果 与S组比较,I/R组后肢运动功能评分降低,p-Akt和p-ERK1/2表达上调,凋亡指数升高(P<0.05);与I/R组比较,LP组后肢运动功能评分升高,p-Akt和p-ERK1/2表达上调,凋亡指数降低(P<0.05).LP组脊髓组织病理学损伤程度轻于I/R组.结论 控制性低压灌注减轻兔脊髓缺血再灌注损伤的机制与激活Akt及ERK1/2,抑制神经元凋亡有关.     

促红细胞生成素对脊髓缺血再灌注损伤保护作用及其机理的实验研究

目的:探讨促红细胞生成素(EPO)处理对脊髓缺血再灌注损伤的保护作用及其可能的作用机理.方法:建立兔脊髓缺血再灌注损伤模型,通过动物神经运动功能评分和组织学染色评价神经损伤程度;采用免疫组织化学染色测量bcl-2和bax蛋白表达情况;TUNEL法检测脊髓细胞凋亡情况.结果:EPO处理组能明显改善动物的神经运动功能并减轻脊髓由于缺血再灌注所引起的病理性损害:EPO组与对照组相比,脊髓前角细胞的凋亡指数明显下降(P＜0.05),脊髓内bcl-2表达增高(P＜0.01),而bax蛋白表达下降(P＜0.01).结论:EPO对脊髓由于缺血而引起的神经运动功能损害具有保护作用,此种保护作用与EPO能够上调bcl-2和下调bax蛋白表达有关.     

Erdosteine ameliorates neurological outcome and oxidative stress due to ischemia/reperfusion injury in rabbit spinal cord.

OBJECTIVE: Oxygen-derived free radicals have been suggested as important in degeneration after spinal cord ischemia. The aim of this study was to investigate whether erdosteine has a protective effect against spinal cord ischemia during aortic cross clamping. MATERIALS AND METHODS: New Zealand White rabbits (n=21) were divided into three groups. In the ischemia/reperfusion group (I/R) (n=8), the infrarenal aorta of rabbits was cross clamped for 21 min and then reperfused. In erdosteine group, the administration of erdosteine solution (50 mg/kg) was started two days before aortic cross-clamping and rabbits (n=8) were subjected to ischemia and reperfusion. Animals in control group (n=5) underwent a surgical procedure similar to the other groups but the aorta was not clamped. The animals were sacrificed at 72 h and histopathological, and biochemical analyses were carried out on the lumbar spinal cords. RESULTS: Erdosteine treatment was associated with improved neurological function in the postoperative period. Histopathological examination of spinal cord tissues in erdosteine group revealed changes consistent with mild ischemic injury, but rabbits in I/R group with paraplegia had total destruction of the motor neurons. Biochemical analyses of spinal cord tissues, in the I/R group, revealed a significant increase in the superoxide dismutase, xanthine oxidase, adenosine deaminase and myeloperoxidase activities, and a significant depletion in glutathione peroxidase activity when compared to that of control rabbits. Erdosteine treatment prevented the increase of all these enzymes except adenosine deaminase. Ischemia/reperfusion produced a significant increase in the tissue malondialdehyde levels. Ischemia/reperfusion-induced increments in malondialdehyde content of the spinal cord were significantly prevented by erdosteine treatment. CONCLUSIONS: The present study demonstrated that erdosteine treatment before aortic cross clamping ameliorates neurological outcome, neuronal injury and oxidative stress in the rabbit spinal cord.     

ROS和PI3K-Akt在缺血后处理或控制性低压灌注减轻大鼠脊髓缺血再灌注损伤中的作用

目的 探讨活性氧自由基(ROS)和磷酸酰肌醇3激酶-蛋白激酶B(PI3K-Akt)在缺血后处理或控制性低压灌注减轻大鼠脊髓缺血再灌注损伤中的作用.方法 雄性SD大鼠126只,体重300～350 g,随机分为7组(n=18),缺血再灌注组(I/R组)阻断胸主动脉同时维持MAP40 mm Hg持续9 min进行脊髓缺血,胸主动脉开放后使MAP升至100 mm Hg进行脊髓再灌注;缺血后处理组(IP组)开放主动脉后,进行再灌注30 s缺血30 s,重复3次,同时维持MAP 100 mm Hg;控制性低压灌注组(LR)开放主动脉后维持MAP 40 mm Hg持续5 min后升高至100 mm Hg;缺血后处理+PI3K抑制剂LY-294002组(IP+L组)和控制性低压灌注+LY-294002组(LR+L组)分别于实施缺血后处理和控制性低压后立即动脉注射LY-294002 25 mg/kg;缺血后处理+氧自由基清除剂N-乙酰半胱氨酸组(IP+N组)和控制性低压灌注+N-乙酰半胱氨组(LR+N组)分别于实施缺血后处理和控制性低血压后立即动脉注射N-乙酰半胱氨酸100 mg/kg.于再灌注2 h时,各组处死12只大鼠,取腰段脊髓组织,测定胞浆Akt磷酸化水平和线粒体通透性转换孔(mPTP)开放程度.分别于再灌注4、12、24、48 h进行神经行为学评分,然后处死大鼠,取腰段脊髓组织,分别进行脊髓前角正常神经元和凋亡神经元的计数.结果 与I/R组比较,IP组和LR组Akt磷酸化水平升高,mPTP开放程度和神经元凋亡计数降低,神经行为学评分和正常神经元计数升高(P＜0.01);IP组与LR组各指标比较差异无统计学意义(P＞0.05).LY294002和N-乙酰半胱氨酸均可逆转缺血后处理和控制性低压灌注对脊髓的保护作用,引起mPTP开放程度升高(P＜0.01).结论 ROS激活PI3K-Akt进而降低线粒体通透性是缺血后处理或控制性低压灌注减轻大鼠脊髓缺血再灌注损伤的机制.     

Spinal cord protection during aortic occlusion: efficacy of intrathecal tetracaine

Spinal cord ischemia and resultant paraplegia are devastating sequelae in up to 40% of patients undergoing repair of thoracoabdominal aneurysms. We investigated the effect of intrathecal tetracaine on the neurological sequelae of spinal cord ischemia and reperfusion with aortic occlusion. Cocaine-derived anesthetics (lidocaine and its analogues) have been shown to decrease neuronal cell metabolism and also have specific neuronal membrane stabilizing effects. New Zealand white rabbits were anesthetized and spinal cord ischemia was then induced by infrarenal aortic occlusion. Animals were divided into six treatment groups. Tetracaine (groups 2 and 4) or normal saline solution (group 5) was administered intrathecally before aortic cross-clamping. Groups 1 and 3 functioned as controls. Group 6 animals received intravenous thiopental. Rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 25 minutes of aortic occlusion produced varied neurological sequelae (group 1, 3/6 injured, 50%) whereas 30 minutes resulted in more consistent injury (group 3, 5/6 injured, 83%). All rabbits that received intrathecal saline solution were paralyzed (group 5, 4/4 injured, 100%). Animals treated with intrathecal tetracaine and aortic occlusion of 30 minutes (group 4) showed significantly better preservation of neurological function (6/7 normal, 86%) than controls and saline-treated animals (groups 3 and 5). All animals treated with intrathecal tetracaine and aortic occlusion for 25 minutes (group 2) showed no signs of injury (5/5 normal, 100%), but this was not significant versus controls (group 1). Intravenous thiopental (group 6, 5/5 injured, 100%) had no beneficial effect. Intrathecal tetracaine significantly and dramatically abrogated the neurological injury secondary to spinal cord ischemia and reperfusion after aortic occlusion at 30 minutes in the rabbit model.     

芦荟多糖对脊髓缺血损伤的神经保护作用

目的:探讨芦荟多糖(aloe polysaccharide,AP)对兔脊髓缺血损伤是否有神经保护作用.方法:32只成年雄性新西兰兔随机分成4组(每组8只 ),即对照组(C 组)、芦荟多糖组(A组)、溶剂对照组( V组 ) 及假手术组(S组).A组在脊髓缺血前30min经耳缘静脉给予50m·kg-1芦荟多糖;V组以同样方式给予等容量生理盐水;C组仅仅制备脊髓缺血损伤模型,不进行其它处理;S组仅仅暴露腹主动脉,而不阻断它,其他处理同C组;兔脊髓缺血模型采用夹闭兔腹主动脉肾下段20min.再灌注后48h,对所有动物神经功能评分,然后处死动物取脊髓(L5-7),制作标本行组织病理学观察.结果:A组的神经功能评分和脊髓前角正常神经细胞数明显多于C组及V组(P<0.01);C组及V组的神经功能评分和脊髓前角正常神经细胞数组间无明显差异(P>0.05);神经功能评分与其对应脊髓前角正常神经细胞计数之间有显著相关性(r=0.804,P<0.01).结论:芦荟多糖对兔脊髓缺血再灌注损伤有明显的神经保护作用.     

Aortic cross-clamping-induced spinal cord oxidative stress in rabbits: the role of a novel antioxidant adrenomedullin

BACKGROUND: Spinal cord injury remains a devastating complication of thoracic and thoracoabdominal aortic operations. We aim to investigate the neuro-protective role of adrenomedullin (AM) administered to rabbits before ischemia and during reperfusion against ischemia-reperfusion (I/R) injury. MATERIALS AND METHODS: Occlusion of the abdominal aorta was applied to adult rabbits, followed by removal of aortic clamp and reperfusion. The abdominal aortas of New Zealand white albino rabbits were occluded for 30 min. Experimental groups were as follows: control group (sham operation group, n = 10), I/R group (n = 9) undergoing occlusion but receiving no pharmacologic intervention, AM-treated group (n = 8) receiving 0.05 microg/kg/min AM intravenously 10 min before ischemia and during reperfusion. Neurological status was assessed at 6, 24, and 48 h after the operation. All animals were killed at 48 h after the operation. Spinal cords were harvested for histopathologic and biochemical analyses. RESULTS: According to Tarlov's scale, neurological status of the rabbits at postoperative hour 48 was better in the AM-treated group compared to the I/R group (P < 0.05). Decreased tissue and serum malondialdehyde levels and increased tissue and serum glutathione levels were observed in the AM-treated group (P < 0.05). In the same group tissue and serum nitrate levels were decreased (P < 0.05). Histopathologic analyses demonstrated typical morphological changes characteristic of necrosis in the I/R group. AM attenuated ischemia-induced necrosis. CONCLUSION: To our knowledge, this is the first study that shows the effects of AM administered both preischemic and during reperfusion on induced oxidative damage to injured spinal cords. AM administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.     

尾静脉注射bFGF对大鼠脊髓损伤的早期影响

目的:比较不同途径应用碱性成纤维细胞生长因子(basicfibroblastgrowthfactor,bFGF)对大鼠脊髓损伤早期水、钙、镁离子的影响,探讨静脉应用bFGF的可行性。方法:AllenWD(Weightdrop)技术,以10g×25cm致伤力造成大鼠T8急性脊髓不完全损伤,不同途径用药比较。术后2h、6h及24h切取伤区脊髓组织检测水、钙、镁离子变化。结果:受损伤脊髓组织水含量增多,钙离子水平增高,镁离子水平下降,而蛛网膜下腔应用bFGF及尾静脉注射bFGF均能明显改变上述变化。结论:脊髓损伤早期静脉应用bFGF同样对脊髓损伤具有保护作用。     

Neuroprotective effect of N-acetylcysteine and hypothermia on the spinal cord ischemia-reperfusion injury

The purpose of this study was to investigate the effect of N-acetylcysteine (NAC) on spinal cord ischemia-reperfusion (I-R) in rabbits. Thirty rabbits were divided into five equal groups, group I (sham-operated, no I-R), group II (control, only I-R), group III (I-R+NAC), group IV (I-R+hypothermia), group V (I-R+NAC+hypothermia). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. Forty-eight hours postoperatively, the motor function of the lower limbs was evaluated in each animal according to Tarlov Score. Spinal cord samples were taken to evaluate the histopathological changes. The sham-operated rabbits (group I) showed no neurologic deficit (Score=4). Paraplegia (Score=0) developed in all rabbits in the control group (group II). Administration of 50 mg/kg of NAC (group III) resulted in significant reduction of motor dysfunction (Score=3.1+/-1.3, p=0.002). Application of hypothermia alone (group IV) showed significant recovery of motor functions (Score=3.0+/-1.1, p=0.002), and combination of hypothermia and 50 mg/kg of NAC (group V) showed complete recovery of lower limb motor function (Score=4, p=0.001). Histologic examination of the spinal cord in rabbits with paraplegia revealed several injured neurons. The cords of animals with no motor function deficits showed only minimal cellular infiltrates in the gray matter, and there was good preservation of nerve cells. NAC showed protective effects of the spinal cord. Moderate hypothermia alone also showed protective effects. Combined use of NAC and hypothermia resulted in highly significant recovery of spinal cord function.     

Effect of Cerebrospinal Fluid Drainage and/or PartiaI Exsanguination on Tolerance to Prolonged Aortic Cross-Clamping

Paraplegia as a consequence of spinal cord ischemia associated with procedures on the thoracic and thoracoabdominai aorta has been linked to the interaction of proximal hypertension with elevated cerebrospinal fluid pressure (CSFP) during aortic cross-clamping (AXC). CSFP reduction via cerebrospinal fluid (CSF) drainage is thought to significantly prolong the cord's tolerance to AXC. Likewise, partial exsanguination is reported to effectively reduce ischemic injury by controlling proximal hypertension. To evaluate the individual and collective efficacy of both techniques, 18 mongrel dogs (25 to 35 kg), divided into three equal groups, underwent a fourth interspace left thoracotomy AXC. Baseline proximal arterial blood pressure (PABP), distal arterial blood pressure (DABP), and CSFP were established and monitored at 5-minute intervals during 120 minutes of AXC, and for 30 minutes thereafter. Group I animals were partially exsanguinated prior to AXC to maintain PABP at a mean of 115 to 120 mmHg. Group II animals had sufficient (16 ± 5 cc) CSF withdrawn to maintain a DABP-CSFP gradient, i.e., spinal cord perfusion pressure (SCPP) of 20 mmHg. Group III animals were treated with both CSF drainage and partial exsanguination in the same manner as groups I and II, respectively. Periop-erative somatosensory evoked potential (SEP) monitoring evaluated cord function. Postoperative neurological outcome was assessed with Tariov's criteria. SEPs degenerated approximately 22 minutes following AXC for groups II and III. In contrast, group I exhibited rapid (10 ± 7 min) SEP loss. All five surviving group I animals displayed paralysis 48 hours postopera-tively. Mean PABP was significantly higher in group II (155 ±18 mmHg) than in either group 1 (117 ± 9 mmHg) or Ill (120 ± 14 mmHg) (p < 0.001). CSFP was significantly higher in group I (14 ± 4 mmHg) than in either group II or III (5 ± 2 mmHg) (p < 0.0001). The only parameter associated with neurological injury was low SCPP, which inversely correlated with CSF dynamics. Group I animals, with a mean SCPP of 4.6 mmHg, exhibited paraplegia, while groups II and Ill, with SCPP values above 20 mmHg, were free of neurological injury. Proximal hypertension did not play a role in cord injury. This study underscores the potential of CSF drainage to protect the ischemic spinal cord. (J Card Surg 7994;9:637–637)     

How DMSO, a widely used solvent, affects spinal cord injury

The aim of this experimental study was to investigate whether dimethylsulfoxide (DMSO) has protective effects on spinal cord ischemia-reperfusion (I/R) injury. New Zealand rabbits were enrolled in the study. In addition to the control group, the study group received 0.1 mL/kg DMSO prior to ischemia. Blood samples were taken to obtain nitrite-nitrate levels during the surgical procedure. After neurological evaluation at 24 hr of reperfusion, lumbar spinal cords were removed for electron microscopic evaluation and malondialdehyde and myeloperoxidase measurements. The mean Tarlov score of the DMSO group was higher than that of the control group. Electron microscopic examination was carried out with tissue samples at 24 hr of reperfusion. The DMSO group had better preservation with the electron microscopic scoring compared to the control group. Malondialdehyde and myeloperoxidase levels were decreased in the DMSO group compared to the control group. Nitrite-nitrate levels were also lower in the DMSO group compared to control at 5 and 30 min of reperfusion. This study demonstrates a considerable neuroprotective effect of DMSO on neurological, biochemical, and histopathological analyses during periods of spinal cord I/R injury in rabbits. Although there was a difference between the DMSO and control groups in all measured parameters in our study, this was not statistically significant. DMSO deserves further investigation related with spinal cord ischemia and reperfusion. We should also consider the effect of DMSO when we use it as a solvent or vehicle during experimental I/R models.