钙蛋白酶抑制剂对缺血再灌注损伤脊髓的保护作用

目的 观察大鼠脊髓缺血再灌注损伤后应用钙蛋白酶特异性抑制剂E-64-D,对脊髓神经细胞组织学改变和凋亡的影响及对大鼠后肢运动功能的保护作用.方法 选用纯种雄性成年SD大鼠106只,夹闭右肾动脉分支下腹主动脉30 min,再灌注即刻静脉应用钙蛋白酶特异性抑制剂E-64-D,观察再灌注后3、24、72 h和7 d脊髓损伤节段神经细胞的凋亡及再灌注后24、72h组织病理学改变;对再灌注后72 h的大鼠后肢功能进行评分.结果 脊髓缺血再灌注24 h开始出现神经细胞凋亡现象,脊髓组织出现病理学改变,神经元死亡,胶质细胞增生.应用E-64-D后,凋亡现象和细胞坏死得到抑制,差异有统计学意义(P<0.01).再灌注后72 h后肢功能也得到一定程度的保护.结论 脊髓再灌注损伤后静脉应用E-64-D治疗,可以明显抑制脊髓神经细胞的凋亡,有利于神经元的存活,损伤后3 d大鼠后肢运动功能得到一定程度的改善.     

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.     

Neuroprotective effects of sulforaphane after contusive spinal cord injury

Traumatic spinal cord injury (SCI) leads to oxidative stress, calcium mobilization, glutamate toxicity, the release of proinflammatory factors, and depletion of reduced glutathione (GSH) at the site of injury. Induction of the Keap1/Nrf2/ARE pathway can alleviate neurotoxicity by protecting against GSH depletion, oxidation, intracellular calcium overload, mitochondrial dysfunction, and excitotoxicity. Sulforaphane (SF), an isothiocyanate derived from broccoli, is a potent naturally-occurring inducer of the Keap1/Nrf2/ARE pathway, leading to upregulation of genes encoding cytoprotective proteins such as NAD(P)H: quinone oxidoreductase 1, and GSH-regulatory enzymes. Additionally, SF can attenuate inflammation by inhibiting the nuclear factor-κB (NF-κB) pathway, and the enzymatic activity of the proinflammatory cytokine macrophage inhibitory factor (MIF). Our study examined systemic administration of SF in a rat model of contusion SCI, in an effort to utilize its indirect antioxidant and anti-inflammatory properties to decrease secondary injury. Two doses of SF (10 or 50?mg/kg) were administered at 10?min and 72?h after contusion SCI. SF (50?mg/kg) treatment resulted in both acute and long-term beneficial effects, including upregulation of the phase 2 antioxidant response at the injury site, decreased mRNA levels of inflammatory cytokines (i.e., MMP-9) in the injured spinal cord, inactivation of urinary MIF tautomerase activity, enhanced hindlimb locomotor function, and an increased number of serotonergic axons caudal to the lesion site. These findings demonstrate that SF provides neuroprotective effects in the spinal cord after injury, and could be a candidate for therapy of SCI.     

Neuroprotective effects of Ac.YVAD.cmk on experimental spinal cord injury in rats

BACKGROUND: Apoptosis as a cell death mechanism is important in numerous diseases, including traumatic SCI. We evaluated the neuroprotective effects of Ac.YVAD.cmk and functional outcomes in a rat SCI model. METHODS: Thirty rats were randomized into 3 groups of 10: sham-operated, trauma only, and trauma plus Ac.YVAD.cmk treatment. Trauma was produced in the thoracic region by a weight-drop technique. Group 3 rats received Ac.YVAD.cmk (1 mg/kg, ip) 1 minute after trauma. The rats were killed at 24 hours and 5 days after injury. Efficacy was evaluated with light microscopy and TUNEL staining. Functional outcomes were assessed with the inclined plane technique and a modified version of the Tarlov grading system. RESULTS: At 24 hours postinjury, the respective mean number of apoptotic cells in groups 1, 2, and 3 were 0, 5.26 +/- 0.19, and 0.97 +/- 0.15. Microscopic examination of group 2 tissues showed widespread hemorrhage, edema, necrosis, and polymorphic nuclear leukocyte infiltration and vascular thrombi. Group 3 tissues revealed similar features, but cavitation and demyelination were less prominent than those in group 2 samples at this period. At 5 days postinjury, the respective mean inclined plane angles in groups 1, 2, and 3 were 65.5 +/- 2.09, 42.00 +/- 2.74, and 52.5 +/- 1.77. Motor grading of animals revealed a similar trend. These differences were statistically significant (P < .05). CONCLUSIONS: Ac.YVAD.cmk inhibited posttraumatic apoptosis in a rat SCI model. This may provide the basis for development of new therapeutic strategies for the treatment of SCI.     

Neuroprotective effects of L-carnitine and vitamin E alone or in combination against ischemia-reperfusion injury in rats

BACKGROUND: Neurological injury because of transient cerebral ischemia is a potential complication of cardiovascular surgery. In this study, the neuroprotective effects of L-carnitine, vitamin E, and the combination of these agents on ischemia/reperfusion (I/R) injury were determined in a rat model of transient global cerebral I/R. METHODS: Rats were pretreated with L-carnitine (100 mg/kg, i.v.) and vitamin E (50 mg/kg, i. v.), alone or in combination and then subjected to cerebral I/R induced by a four-vessel-occlusion technique for a duration of 15 min followed by 15 min of reperfusion. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and glutathione (GSH) levels were measured in the cerebral tissues. Histopathological examinations were also carried out under light and electron microscopy. RESULTS: The results showed that I/R elevated MDA levels, which were accompanied by a reduction in SOD activities and GSH levels. Surviving neurons was markedly decreased in CA1 and CA3 subfield of hippocampus in I/R animals. L-carnitine, vitamin E, and their combination restored MDA levels and SOD activities, with a tendency to increase surviving neurons in CA1 and CA3 subfield. Combined treatment of L-carnitine and vitamin E had better GSH levels than individual treatment of these agents. CONCLUSIONS: The results suggest that L-carnitine has a potent neuroprotective effect against cerebral-I/R-induced injury in rat brain that is comparable to that of vitamin E. However, the combined use of L-carnitine and vitamin E does not further protect from neuronal injury, although it provides an increase in GSH levels.     

中药黄芪对实验性脊髓损伤的神经保护作用

目的探讨黄芪(AR)对脊髓继发性损伤的保护作用,并与甲基强地松龙(MP)进行对照.方法 Wistar大鼠60只,以改良Allen氏法制备脊髓打击伤模型,随机分为三组.测定不同药物处理后4 h、8 h、24 h脊髓组织线粒体SOD活性和MDA浓度以及血液流变学改变;光镜观察用药后1、2周黄芪对病理学改变的影响,同时进行联合行为学评分(CBS).结果黄芪处理后脊髓组织MDA浓度明显低于各时相点对照组,SOD活性显著升高(P＜0.01),与MP治疗组无明显差异(P＞0.05).血液流变学指标也有所改善.病理检查发现黄芪治疗组髓鞘受损轻微,组织赦免范围增大.结论黄芪治疗可以缓解脊髓损伤后的脂质过氧化反应,改善微循环,从而发挥脊髓保护作用.     

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.     

Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats

Background:

Oxidative stress is a mediator of secondary injury to the spinal cord following trauma.

Objective:

To investigate the putative neuroprotective effect of α-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI).

Methods:

Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique.

Results:

SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged.

Conclusion:

The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.     

淫羊藿苷在大鼠脊髓损伤中的神经保护作用

目的:研究淫羊藿苷在大鼠脊髓损伤中的神经保护作用。方法:108只SPF级雄性3月龄SD大鼠按随机数字表法分为实验组、对照组及假手术组3组,每组36只。对照组和实验组采用改良Allen法制作脊髓损伤模型,假手术组仅切开椎板不损伤脊髓。术后即刻实验组给予淫羊藿苷(100 mg/kg)灌胃,对照组和假手术组给予等量生理盐水灌胃,每日2次。术后1、2、3 d采用BBB评分法评定大鼠运动功能;术后72 h采用分光光度法检测髓过氧化物酶(myeloperoxidase,MPO)的活性,酶联免疫吸附测定(ELISA)法检测肿瘤坏死因子(tumor necrosis factor,TNF)-α、白介素(interleukin,IL)-1β的含量,免疫组化染色检测MPO、TNF-α、IL-1β的表达;采用硫代巴比妥酸法检测丙二醛(malondialdehyde,MDA)含量,黄嘌呤氧化酶法检测超氧化物歧化酶(superoxide dismutase,SOD)活性;采用TUNEL法检测细胞凋亡并计算细胞凋亡指数(apoptosis index,AI);光镜观察脊髓损伤后组织病理学的改变并行组织病理学评分。结果:术后各时间点对照组和实验组大鼠BBB评分均显著低于假手术组(P0.05);术后2、3 d实验组大鼠BBB评分均显著高于对照组(P0.05)。术后72 h,对照组和实验组MPO活性和TNF-α、IL-1β的含量显著高于假手术组(P0.05);实验组显著低于对照组(P0.05)。对照组和实验组MPO、TNF-α、IL-1β的表达显著高于假手术组(P0.05);实验组显著低于对照组(P0.05)。对照组和实验组MDA含量显著高于假手术组,实验组显著低于对照组(P0.05);对照组和实验组SOD活性显著低于假手术组,实验组显著高于对照组(P0.05)。对照组和实验组脊髓组织中AI显著高于假手术组,实验组显著低于对照组(P0.05)。对照组和实验组脊髓组织病理学评分均显著高于假手术组,实验组均显著低于对照组(P0.05)。结论:淫羊藿苷能够抑制脊髓损伤后的炎症、脂质过氧化和细胞凋亡,减轻脊髓组织病理学损伤,改善脊髓损伤大鼠的运动功能,有效保护脊髓组织,具有明显的神经保护作用。     

左旋卡尼汀对离体心肌缺血再灌注损伤的保护作用

目的探讨左旋卡尼汀增补于停搏液中对离体鼠心再灌注损伤的保护作用。方法将32只SD大鼠随机分为左旋卡尼汀3个剂量(2．5、5．0、10．0 mmol／L)组和对照组。离体鼠心在改良的Langendorff灌注模型上30 min预灌注,120 min缺血、60 min再灌注。缺血前及再灌注期间测定血流动力学指标、心肌超氧化物歧化酶(SOD)、丙二醛(MDA)含量和三磷酸腺苷(ATP)水平。电镜观察心肌超微结构。结果再灌注60 min后,左旋卡尼汀5 mmol／L剂量组和10 mmol／L剂量组与对照组相比,冠脉流量(CF)[(68．39±12．71)％、(72．27±6．27)％比(44．94±13．26)％]、左室收缩压(LVSP)[(73．04±3．32)％、(77．8±3．80)％比(62．29±4．14)％]、左室舒张末压(LVEDP)[(0．38±0．01)、(0．36±0．01)比(0．43±0．01)mmHg(1mmHg=0．133 kPa)]、左室压力变化速率(+dp／dt)[(69．66±0．92)％、(71．34±0．66)％比(62．16±1．21))％]、(-dp／dt) [(68．39±12．71)％、(72．27±6．27)％比(44．94±13．26)％],其差异均有统计学意义(P＜0．01)。心肌超微结构的改善,也优于对照组,尤其是10 mmol／L剂量组,2．5 ml／L组没有变化。左旋卡尼汀5 mmol／L剂量组和10 mmol／L剂量组丙二醛(MDA)含量显著低于对照组(19．04±0．41)、(17．60±0．53)nmol／mg蛋白比(27．36±1．23)nmol／mg蛋白,P＜0．01),超氧化物歧化酶(SOD) [(218．20±14．91)、(238．63±7．61)U／mg蛋白比(141．80±15．17)U／mg蛋白]含量和三磷酸腺苷(ATP)水平[(3．83±0．20)、(5．26±0．18)μmol／L比(1．36±0．08)μmol／L]显著高于对照组(P＜0．01)。结论左旋卡尼汀(5～10 mmol／L)增补于停搏液中可减轻心肌缺血再灌注损伤,具有良好的心肌保护作用并在一定范围内呈剂量依赖性,10mmol／L剂量组心肌保护效果最佳。     

Neuroprotective effects of racemic ketamine and (S)-ketamine on spinal cord injury in rat

BackgroundThe aim of this study was to investigate and to compare the potential neuroprotective effects of racemic ketamine, (S)-ketamine and methylprednisolone after an experimental spinal cord injury model in rats.MethodsFifty-nine Wistar albino rats were divided into three main groups as acute stage (A), subacute stage (SA) and sham groups and then acute and subacute stage groups were divided into four groups regarding the used drug as control (CONT), racemic ketamine (RK), (S)-ketamine (SK) and methylprednisolone (MP) groups. A dorsal laminectomy was performed; and spinal cord injury was induced by using a temporary aneurysm clip. Four hours later from the clip compression, except those of the sham and control groups, the drugs (60 mg/kg racemic ketamine, 60 mg/kg (S)-ketamine or 30 mg/kg methylprednisolone) were administered intraperitoneally. At 72th h and 7th days of the study, the spinal cords of rats were removed from T8 level to the conus medullaris level. The specimens were and evaluated histopathologically, tissue lipid peroxidation (LPO) and myeloperoxidation (MPO) levels were measured and biochemically.ResultsThe histopathological results were similar both in the acute and in the subacute stage groups. There was a statistically significant difference among all groups regarding the tissue LPO levels (p < 0.001). There was a statistically significant difference between the CONT-A group and the MP-A, RK-A and SK-A groups (p = 0.004, p < 0.001 and p = 0.007, respectively) in acute stage and between the CONT-SA group and SK-SA group (p = 0.002) in subacute stage. There was a statistically significant difference among all groups regarding the tissue MPO levels (p = 0.001). The median MPO levels were similar among acute stage groups (p = 0.057), but there was a statistical difference among subacute stage groups (p = 0.046).Conclusion(S)-ketamine is more effective than methylprednisolone and racemic ketamine to reduce the LPO levels in subacute stage of spinal cord injury in rats. And, it is as effective as methylprednisolone in preventing secondary spinal cord injury histopathologically.     

左卡尼汀减轻大鼠肾缺血再灌注损伤及其机制的研究

目的 研究左卡尼汀对大鼠肾缺血再灌注损伤(IRI)的影响及其机制.方法 将Wistar大鼠分为3组:L组大鼠制成IRI模型,于夹闭肾动静脉前5 min及松开动脉夹后30 min,分2次经尾静脉注射左卡尼汀,各500mg/kg;I组大鼠制成IRI模型,仅注射生理盐水;C组仅分离双侧肾动、静脉,注射生理盐水.分别于再灌注后3、6和24 h处死各组大鼠.处死前经下腔静脉取血,检测血清肌酐(Cr)、尿素氮( BUN)、超氧化物歧化酶(SOD)及丙二醛(MDA)含量.获取肾组织样本,进行病理学观察;应用逆转录聚合酶链反应检测肾组织核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、γ-谷氨酰半胱氨酸合成酶(γ-GCS)的mRNA水平;蛋白质印迹法检测细胞核中Nrf2含量;免疫组织化学法检测肾组织中Nrf2的表达及定位.结果 再灌注后3h时,L组与I组血清Cr和BUN均高于C组(P＜0.01);再灌注后6h时,L组血清Cr和BUN高于C组(P＜0.01),而低于I组(P＜0.01);再灌注后24 h时,L组血清Cr和BUN仍低于I组(P＜0.05).再灌注后6和24 h时,L组与I组SOD水平低于C组(P＜0.05),MDA水平高于C组(P＜0.05).再灌注后各时间点,L组SOD水平均高于I组(P＜0.05),MDA水平均低于I组(P＜0.05).再灌注后24 h时,L组肾组织病理改变较I组轻.再灌注后6h时,I组Nrf2、HO-1、γ-GCS的mRNA相对含量均高于C组(P＜0.05),而L组各基因mRNA的相对含量高于I组(P＜0.05).L组细胞核内Nrf2的相对含量高于I组(P＜0.05).结论 左卡尼汀可减轻大鼠肾脏IRI,其机制可能与激活Nrf2-ARE通路,进而增强下游抗氧化基因的表达有关.     

Neuroprotective effects of basic fibroblast growth factor following spinal cord contusion injury in the rat.

Cytokines and neurotrophic factors have been implicated in the pathophysiology of injury to the central nervous system. While some cytokines are considered pro-inflammatory, other factors promote neuronal growth and survival. The present study investigated the neuroprotective effects of interleukins 1 (IL-1), 4 (IL-4), and 6 (IL-6), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF) in a contusion model of spinal cord injury. Female Sprague-Dawley rats (n = 55) sustained a 10-g weight-drop injury to the lower thoracic spinal cord (T10) from a height of 12.5 mm using the NYU impactor. A micro-infusion system (Alzet minipump) was used to continuously deliver drugs or vehicle directly into the epicenter of the contused spinal cord starting 1 or three h postinjury. At the end of 7 days, animals were perfused and the cords removed for histopathological analysis. Longitudinal serial sections were cut on a freezing microtome and stained with cresyl violet. Areas of central necrosis, partial preservation, and total zone of tissue injury were identified and traced by an independent reviewer using a computer based imaging system. The mean total zone of injury in five animals receiving vehicle infusion was 18.04+/-4.20 mm3. The mean zone of partial preservation in these animals was 16.46+/-3.32 mm. Basic fibroblast growth factor reduced the total zone of injury by 33% [p<0.01, least significant difference (LSD) of Fisher] in five animals and the zone of partial preservation by 32% (p<0.01, LSD of Fisher) when compared to controls. There were trends toward reduction in total zone of injury and zone of partial preservation in rats treated with IL-4, CNTF, and NGF versus vehicle; however, none of these reached statistical significance. No significant differences were observed between animals receiving vehicle versus bFGF treatment commencing 3 h after injury. These data demonstrate that the continuous intramedullary infusion of bFGF initiated one hour after moderate contusion injury of the spinal cord significantly reduces the total zone of injury and the zone of partial preservation. These results support the further investigation and possible future clinical application of bFGF in the treatment of acute spinal cord contusion injury.     

Neuroprotective effects of recombinant thrombomodulin in controlled contusion spinal cord injury implicates thrombin signaling

Although the central nervous system (CNS) of mammals has had poor prospects for regeneration, recent studies suggest this might improve from blocking "secondary cell loss" or apoptosis. In this regard, intravenous activated protein C (aPC) improved neurologic outcomes in a rat compression spinal cord injury (SCI) model. Protein C activation occurs when the serine protease thrombin binds to the cell surface proteoglycan thrombomodulin (TM) forming a complex that halts coagulation. In culture, rTM blocks thrombin's activation of protease-activated receptors (PARs), that mediate thrombin killing of neurons and glial reactivity. Both PAR1 and prothrombin are rapidly upregulated after contusion SCI in rats, prior to peak apoptosis. We now report neuroprotective effects of intraperitoneal soluble recombinant human rTM on open-field locomotor rating scale (BBB) and spinal cord lesion volume when given 1 h after SCI. BBB scores from four separate experiments showed a 7.6 +/- 1.4 absolute score increase (p < 0.05) at 3 days, that lasted throughout the time course. Histological sections at 14 days were even more dramatic where a twofold reduction in lesion volume was quantified in rTM-treated rats. Thionin staining revealed significant preservation of motor neuronal profiles both at, and two segments below, the lesion epicenter. Activated caspase-3 immunocytochemistry indicated apoptosis was quite prominent in motor neurons in vehicle (saline) controls, but was dramatically reduced by rTM. Microglia, increased and activated after injury, were reduced with rTM treatment. Taken together, these and previous results support a prominent role for coagulation-inflammation signaling cascades in the subacute changes following SCI. They identify a neuroprotective role for rTM by its inhibition of thrombin generation and blockade of PAR activation.     

Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping

BACKGROUND AND AIM OF THE STUDY: The new calcium sensitizer, levosimendan, not only acts as a positive inotropic agent but also, vasodilates both venules and arterioles. The aim of this experimental study was to investigate whether levosimendan has protective effects on spinal cord ischemia-reperfusion injury. MATERIAL AND METHODS: Twelve New Zealand rabbits were enrolled in this study. In addition to the control group, levosimendan is administered to the experimental group with a loading dose of 12 microg/kg prior to ischemia over a 10-minute period, followed by an infusion of 0.2 microg/kg/min during the ischemia period (30-minutes). Following the neurologic evaluation at the 24th hour of reperfusion, lumbar spinal cords were removed in order to perform microscopic examination and malondialdehyde (MDA) and myeloperoxidase (MPO) measurements. RESULTS: The mean Tarlov score of the levosimendan group (3.25) was higher than the control group (0.7) (p< 0.05). MDA level was found significantly lower in the levosimendan group when compared with the control group as 1.6 +/- 0.4 nmol/gr and 189.3 +/- 43.6 nmol/gr respectively (p < 0.05). MPO level was also found statistically significant when we compared levosimendan group with the control group. It was calculated as 11.3 +/- 1.0 micro/gr tissue and 39.1 +/- 16.9 micro/gr in the levosimendan and the control groups (p< 0.05). Light microscopic examination was carried out with tissue samples in the 24th hour of the reperfusion. Levosimendan group had better preservation with the microscopic appearance with respect to the control group. CONCLUSION: Levosimendan exhibits an important protection by means of neurological outcome, histopathological, and biochemical analysis for the ischemia-reperfusion injury of the spinal cord following the aortic clamping.