Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia.

BACKGROUND: Ischemic preconditioning (IPC) is an endogenous cellular protective mechanism whereby brief, noninjurious periods of ischemia render a tissue more resistant to a subsequent, more prolonged ischemic insult. We hypothesized that IPC of the spinal cord would reduce neurologic injury after experimental aortic occlusion in rats and that this improved neurologic benefit could be induced acutely after a short reperfusion interval separating the IPC and the ischemic insult. METHODS: Forty male Sprague-Dawley rats under general anesthesia were randomly assigned to one of two groups. The IPC group (n = 20) had 3 minutes of aortic occlusion to induce spinal cord ischemia 30 minutes of reperfusion, and 12 minutes of ischemia, whereas the controls (n = 20) had only 12 minutes of ischemia. Neurologic function was evaluated 24 and 48 hours later. Some animals from these groups were perfusion-fixed for hematoxylin and eosin staining of the spinal cord for histologic evaluation. RESULTS: Survival was significantly better at 48 hours in the IPC group. Sensory and motor neurologic function were significantly different between groups at 24 and 48 hours. Histologic evaluation at 48 hours showed severe neurologic damage in rats with poor neurologic test scores. CONCLUSIONS: Ischemic preconditioning reduces neurologic injury and improves survival in a rat model of spinal cord ischemia. The protective benefit of IPC is acutely invoked after a 30-minute reperfusion interval between the preconditioning and the ischemic event.     

Superiority of early relative to late ischemic preconditioning in spinal cord protection after descending thoracic aortic occlusion

OBJECTIVE: We previously showed that ischemic preconditioning significantly reduced spinal cord injury caused by 35-minute aortic occlusion. In this study we investigated the effect of ischemic preconditioning on spinal cord injury after 45-minute aortic occlusion. METHODS: Thirty-two pigs were divided as follows: group 1 (n = 6) underwent sham operation, group 2 (n = 6) underwent 20 minutes of aortic occlusion, group 3 (n = 6) underwent 45 minutes of occlusion, group 4 (n = 6) underwent 20 minutes of occlusion and 48 hours later underwent an additional 45 minutes, and group 5 (n = 8) underwent 20 minutes of occlusion and 80 minutes later underwent an additional 45 minutes. Aortic occlusion was accomplished with two balloon occlusion catheters placed fluoroscopically after the origin of the left subclavian artery and at the aortic bifurcation. Neurologic evaluation was by Tarlov score. The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin-eosin staining. The number of neurons was counted, and the inflammation was scored (0-4). Statistical analysis was by Kruskal-Wallis and 1-way analysis of variance tests. RESULTS: Group 5 (early ischemic preconditioning) had better Tarlov scores than group 3 ( P < .001) and group 4 (late ischemic preconditioning, P < .001). The histologic changes were proportional to the Tarlov scores, with the least histologic damage in the animals of group 5 relative to group 3 (number of neurons P < .001, inflammation P = .004) and group 4 (number of neurons P < .001, inflammation P = .006). CONCLUSION: Early ischemic preconditioning is superior to late ischemic preconditioning in reducing spinal cord injury caused by the extreme ischemia of 45 minutes of descending thoracic aortic occlusion.     

NS-7, a novel Na+/Ca2+ channel blocker, prevents neurologic injury after spinal cord ischemia in rabbits

OBJECTIVE: We investigated the neuroprotective effect of NS-7 (4-[4-fluorophenyl]-2-methyl-6- [5-piperidinopntyloxy] pyrimidine hydrochloride), a novel Na(+)/Ca(2+) channel blocker, on transient spinal cord ischemia in rabbits. METHODS: Spinal cord ischemia was induced in New Zealand white rabbits by means of infrarenal aortic occlusion for 20 minutes. Four experimental groups were enrolled. A sham group (n = 3) underwent the same operation without aortic occlusion. A control group (n = 7) received only saline before occlusion. Group A (n = 8) received NS-7 (1 mg/kg) 15 minutes before ischemia, and group B (n = 8) received NS-7 (1 mg/kg) at the onset of reperfusion. Neurologic function was assessed 24 and 48 hours after the operation with modified Tarlov criteria. Spinal cords were harvested for histopathologic examination and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL staining). Spinal cord infarction was investigated with 2, 3, 5-triphenyltetrazonlium chloride staining. RESULTS: Tarlov scoring demonstrated marked improvement in both group A and group B compared with the control group at 24 and 48 hours after the operation. Minimal histologic changes were found in lumbar spinal cords of the 2 NS-7-treated groups, whereas severe neuronal necrosis was shown in the control group. TUNEL-positive neurons and the infarct size of lumbar spinal cords were significantly reduced by NS-7 administered both before ischemia and at the onset of reperfusion. No significant difference was noted between group A and group B in terms of spinal cord protection. CONCLUSION: These results indicate that NS-7 protects the spinal cord against ischemic injury by preventing both neuronal necrosis and apoptosis.     

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.     

Effect of puerarin on neural function and histopathological damages after transient spinal cord ischemia in rabbits

Ischemicspinalcordinjuryremainsadisastrouscomplicationofthedescendingandthoracoabdominalaortaeafteroperation .Thereportedincidenceofparaplegiarangesfrom 4 %to 33% .1Therefore ,agreatnumberofeffortshavebeenfocusedonsolvingthisproblem ,whichincludehypothermia ,cerebrospinalfluiddrainage ,temporarybypassandpharmacologicalagents .2 Thecellularandmolecularmechanismsofischemicspinalcordinjuryhavenotbeentotallyelucidated .Butvariousstudieshavesuggestedthatfreeradicalproduction ,calciumaccumulationand…     

Effects of xenon on ischemic spinal cord injury in rabbits: a comparison with propofol

Background: Xenon has been shown to reduce cellular injury after cerebral ischemia. However, the neuroprotective effects of xenon on ischemic spinal cord are unknown. The authors compared the effects of xenon and propofol on spinal cord injury following spinal cord ischemia in rabbits. Methods: Thirty‐two male New Zealand white rabbits were randomly assigned to one of three groups. In the xenon and propofol group, 70% of xenon and 0.8 mg/kg/min of propofol were administered 30 min before an aortic occlusion and maintained until the end of the procedure. The aortic occlusion was performed for 15 min. In the sham group, the aorta was not occluded. After an assessment of the hind limb motor function using the Tarlov score (0=paraplegia, 4=normal) at 48 h after reperfusion, gray and white matter injuries were evaluated based on the number of normal neurons in the anterior spinal cord and the percentage areas of vacuolation in the white matter, respectively. Results: In the xenon and propofol groups, the Tarlov score and the number of normal neurons were significantly lower than those in the sham group, whereas the percentage areas of vacuolation were similar among the three groups. There were no significant differences in Tarlov scores and the number of normal neurons between the xenon and the propofol groups. Conclusion: The results indicated that 70% of xenon has no additional neuroprotective effects on ischemic spinal cord injury in rabbits compared with propofol.     

Evolution of spinal cord injury in a porcine model of prolonged aortic occlusion

BACKGROUND: Spinal cord injury and subsequent paraplegia remains an unpredictable and devastating complication of thoracoabdominal aortic surgery. The aim of this study was to investigate spinal cord injury due to prolonged thoracoabdominal aortic occlusion. MATERIALS AND METHODS: We used a highly reproducible porcine model of 45-min thoracoabdominal aortic occlusion, which was accomplished by two balloon occlusion catheters. Neurological evaluation after the end of experiment was performed by an independent observer according to the Tarlov scale. The lower thoracic and lumbar spinal cords were harvested at 10, 48, and 120 h (n = 6 animals per time point) and examined histologically with hematoxylin and eosin (H&E) stain and TUNEL method. Tarlov scores, number of neurons, and the grade of inflammation were analyzed. RESULTS: H&E staining revealed reduction in the number of motor neurons which occurred in two phases (between 0 and 10 h and between 48 and 120 h of reperfusion), as well as development of inflammation in spinal cord sections during the reperfusion period, reaching a peak at 48 h. TUNEL reaction was negative for apoptotic neurons at any time point. CONCLUSIONS: In this porcine model, we demonstrated that, after 45 min of thoracoabdominal aortic occlusion, motor neuron death seems to occur in two phases (immediate and delayed). Inflammation was a subsequent event of transient prolonged spinal cord ischemia and possibly a major contributor of delayed neuronal death. Using TUNEL straining we found no evidence of neuronal apoptosis at any time point of reperfusion.     

Evaluation of rapid ischemic preconditioning in a rabbit model of spinal cord ischemia

BACKGROUND: Rapid ischemic preconditioning (IPC) has been shown to reduce cellular injury after subsequent cardiac and cerebral ischemia. However, the data on rapid IPC of the spinal cord is limited. The authors investigated whether pretreatment with sublethal ischemia of spinal cord can attenuate neuronal injury after spinal cord ischemia in rabbits. METHODS: Forty-seven male New Zealand white rabbits were randomly assigned to one of three groups (n = 15 or 16 each). In the IPC(-) group, the infrarenal aorta was occluded for 17 min to produce spinal cord ischemia. In the IPC(+) group, 5 min of aortic occlusion was performed 30 min before 17 min of spinal cord ischemia. In the sham group, the aorta was not occluded. Hind limb motor function was assessed at 3 h, 24 h, 4 days, and 7 days after reperfusion using Tarlov scoring (0 = paraplegia; 4 = normal). Animals were killed for histopathologic evaluation at 24 h or 7 days after reperfusion. The number of normal neurons in the anterior spinal cord (L4-L6) was counted. RESULTS: Neurologic scores were significantly higher in the IPC(+) group than the IPC(-) group at 3 and 24 h after reperfusion (P < 0.05). However, neurologic scores in the IPC(+) group gradually decreased and became similar to those in the IPC(-) group at 4 and 7 days after reperfusion. At 24 h after reperfusion, the numbers of normal neurons were significantly higher in the IPC (+) group than in the IPC(-) group (P < 0.05) and were similar between the IPC(+) and sham groups. At 7 days after reperfusion, there was no difference in the number of normal neurons between the IPC(+) and IPC(-) groups. CONCLUSION: The results indicate that rapid IPC protects the spinal cord against neuronal damage 24 h but not 7 days after reperfusion in a rabbit model of spinal cord ischemia, suggesting that the efficacy of rapid IPC may be transient.     

Evaluation of Rapid Ischemic Preconditioning in a Rabbit Model of Spinal Cord Ischemia

Background: Rapid ischemic preconditioning (IPC) has been shown to reduce cellular injury after subsequent cardiac and cerebral ischemia. However, the data on rapid IPC of the spinal cord is limited. The authors investigated whether pretreatment with sublethal ischemia of spinal cord can attenuate neuronal injury after spinal cord ischemia in rabbits.

Methods: Forty-seven male New Zealand white rabbits were randomly assigned to one of three groups (n = 15 or 16 each). In the IPC(-) group, the infrarenal aorta was occluded for 17 min to produce spinal cord ischemia. In the IPC(+) group, 5 min of aortic occlusion was performed 30 min before 17 min of spinal cord ischemia. In the sham group, the aorta was not occluded. Hind limb motor function was assessed at 3 h, 24 h, 4 days, and 7 days after reperfusion using Tarlov scoring (0 = paraplegia; 4 = normal). Animals were killed for histopathologic evaluation at 24 h or 7 days after reperfusion. The number of normal neurons in the anterior spinal cord (L4-L6) was counted.

Results: Neurologic scores were significantly higher in the IPC(+) group than the IPC(-) group at 3 and 24 h after reperfusion (P < 0.05). However, neurologic scores in the IPC(+) group gradually decreased and became similar to those in the IPC(-) group at 4 and 7 days after reperfusion. At 24 h after reperfusion, the numbers of normal neurons were significantly higher in the IPC (+) group than in the IPC(-) group (P < 0.05) and were similar between the IPC(+) and sham groups. At 7 days after reperfusion, there was no difference in the number of normal neurons between the IPC(+) and IPC(-) groups.     

Effect of ischemic post-conditioning on spinal cord ischemic-reperfusion injury in rabbits

OBJECTIVES: To investigate the potential protective effect of ischemic post-conditioning (Post-con) on ischemia-reperfusion injury of the rabbit spinal cord, and to determine if there is an additive neuroprotective effect when ischemic preconditioning (IPC) and Post-con are combined. METHODS: Forty New Zealand white rabbits were randomly divided into four groups: group Control (C; n=10), aortic occlusion (AOC; for 30 min; group IPC (n=10) three cycles of three-minute AOC plus three-minute reperfusion before the 30-min AOC; group Post-con (n=10), three cycles of three-minute reperfusion plus three-minute AOC immediately upon reperfusion after 30-min AOC; group IPC+Post-con (n=10), where animals were subjected to both IPC and Post-con. At six hours, 24 hr and 48 hr following reperfusion, neurological function was assessed according to Tarlov scores, and at 48 hr, the spinal cords were procured for the histopathologic evaluation, by comparing the number of intact alpha-motor neurons in the anterior horn. RESULTS: The median count (and quartiles) of intact alpha-motor neurons was greatest in group Post-con 73 (69-76) and group IPC+Post-con 29 (22-42) compared to the numbers of viable alpha-motor neurons in groups C 6 (4-9) and IPC 15 (11-18) (P < 0.001). The numbers of animals who developed paraplegia according to Tarlov criteria were 7/10 in groups Post-con and IPC+Post-con, compared to 9/10 animals in each of groups C and IPC. CONCLUSIONS: This laboratory investigation provides histological evidence that Post-con may protect the spinal cord from moderate to severe ischemia reperfusion injury. Ischemic preconditioning conferred no additional benefits in this rabbit model. The results have potential clinical implications for patients undergoing thoracoabdominal aortic reconstructive surgery.     

Evaluation of Pulmonary Reperfusion Injury in Rats Undergoing Mesenteric Ischemia and Reperfusion and Protective Effect of Postconditioning on this Process

INTRODUCTION

Some publications have demonstrated the presence of lung reperfusion injury in mesenteric ischemia and reperfusion (I/R), but under to diverse methods. Postconditioning has been recognized as effective in preventing reperfusion injury in various organs and tissues. However, its effectiveness has not been evaluated in the prevention of lung reperfusion injury after mesenteric ischemia and reperfusion.

OBJECTIVE

To evaluate the presence of pulmonary reperfusion injury and the protective effect of ischemic postconditioning on lung parenchyma in rats submitted to mesenteric ischemia and reperfusion.

METHODS

Thirty Wistar rats were distributed into three groups: group A (10 rats), which was held mesenteric ischemia (30 minutes) and reperfusion (60 minutes); group B (10 rats), ischemia and reperfusion, interspersed by postconditioning with two alternating cycles of reperfusion and reocclusion, for two minutes each; and group C (10 rats), ischemia and reperfusion interleaved by postconditioning with four alternating cycles of reperfusion and reocclusion of 30 seconds each. Finally, it was resected the upper lung lobe for histological analysis.

RESULTS

There were mild lung lesions (grade 1) in all samples. There was no statistical difference between groups 1 and 2 (P>0.05).

CONCLUSION

The mesenteric ischemia and reperfusion in rats for thirty and sixty minutes, respectively, caused mild reperfusion injury in lung. Postconditioning was not able to minimize the remote reperfusion injury and there was no difference comparing two cycles of two minutes with four cycles of 30 seconds.     

Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion

BACKGROUND: We hypothesized that inflammation during spinal cord reperfusion worsens ischemic injury. ATL-146e, an adenosine A(2A) agonist with known anti-inflammatory properties, was used to test this hypothesis at varied intervals to determine the time course of reperfusion injury. METHODS: Forty rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group (n = 14 animals) received 0.06 microg/kg/min systemic ATL-146e over 3 hours, beginning after 30 minutes of ischemic time. A second group (n = 6 animals) received ATL-146e over 1.5 hours. A third group (n = 3 animals) received ATL-146e over 1 hour, and a fourth group (n = 17 animals) received saline solution. All animals were assessed at 48 hours for hind limb motor function (Tarlov scale, 0-5). RESULTS: Animals that received ATL-146e for 3 hours (Tarlov score, 4.3 +/- 0.22; P <.001) or 1.5 hours (Tarlov score, 2.7 +/- 0.6; P <.05) had improved neurologic outcomes compared with rabbits that received saline solution (Tarlov score, 0.6 +/- 0.29). Animals that received ATL-146e for 1 hour (Tarlov score, 0.7 +/- 0.8) were not significantly different from those animals that received saline solution. CONCLUSIONS: Systemic ATL-146e, given during reperfusion, results in time-dependent improvement in spinal cord function after ischemia. This implies that the mechanism of spinal reperfusion injury includes leukocyte-mediated inflammation at a critical post-ischemic time interval.     

Peri-ischemic aminoguanidine fails to ameliorate neurologic and histopathologic outcome after transient spinal cord ischemia.

Inhibition of neurotoxic events that lead to delayed cellular damage may prevent motor function loss after transient spinal cord ischemia. An important effect of the neuroprotective substance aminoguanidine (AG) is the inhibition of inducible nitric oxide synthase (iNOS), a perpetrator of focal ischemic damage. The authors studied the protective effects of AG on hind limb motor function and histopathologic outcome in an experimental model for spinal cord ischemia, and related these findings to the protein content of iNOS in the spinal cord. Temporary spinal cord ischemia was induced by 28 minutes of infrarenal balloon occlusion of the aorta in 40 anesthetized New Zealand White rabbits. Animals were assigned randomly to two treatments: saline (n = 20) or AG (n = 20; 100 mg/kg intravenously before occlusion). Postoperatively, treatment was continued with subcutaneous injections twice daily (saline or 100 mg/kg AG). Normothermia (38 degrees C) was maintained during ischemia, and rectal temperature was assessed before and after subcutaneous injections. Animals were observed for 96 hours for neurologic evaluation (Tarlov score), and the lumbosacral spinal cord was examined for ischemic damage after perfusion and fixation. Lastly, iNOS protein content was determined using Western blot analysis 48 hours after ischemia in five animals from each group. Neurologic outcome at 96 hours after reperfusion was the same in both groups. The incidence of paraplegia was 67% in the saline-treated group versus 53% in the AG-treated group. No differences in infarction volume, total number of viable motoneurons, or total number of eosinophilic neurons were present between the groups. At 48 hours after reperfusion, iNOS protein content in the spinal cord was increased in one animal in the AG-treated group and in three animals in the control group. The data indicate that peri-ischemic treatment with high-dose AG in rabbits offers no protection against a period of normothermic spinal cord ischemia. There was no conclusive evidence of spinal cord iNOS inhibition after treatment with AG.     

Systemic adenosine A2A agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord

BACKGROUND: The adenosine A2A agonist ATL-146e (4-[3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxytetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester) has been shown to prevent reperfusion injury in multiple organ systems through inhibition of activated leukocyte-endothelial interaction. We hypothesized that systemic ATL-146e could reduce spinal cord reperfusion injury after aortic clamping. METHODS: Twenty-six rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group received intravenous ATL-146e for 3 hours during reperfusion. A second cohort received only vehicle and served as controls. Animals were assessed at 24 and 48 hours using the Tarlov (0 to 5) scoring system for hind limb function. To evaluate neuronal attrition, immunostaining of lumbar spinal cord sections was performed using anti-SMI 33 antibody against neurofilament. RESULTS: Systemic ATL-146e was tolerated without hemodynamic lability. Animals that received ATL-146e had significantly improved neurologic outcomes 24 and 48 hours after spinal cord ischemia (p < 0.001). There was preservation of neuronal architecture in the ventral horn of spinal cord sections from animals receiving ATL-146e compared with control animals. CONCLUSIONS: Intravenous ATL-146e given during reperfusion is tolerated without hemodynamic lability, and results in substantially improved spinal cord function after ischemia by preservation of ventral horn neurons.     

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.     

Reevaluation of gray and white matter injury after spinal cord ischemia in rabbits

BACKGROUND: Although gray matter injury has been well characterized, the available data on white matter injury after spinal cord ischemia (SCI) in rabbits are limited. The current study was conducted to investigate the evolution of ischemia induced injury to gray and white matter and to correlate this damage to hind-limb motor function in rabbits subjected to SCI. METHODS: Thirty-eight rabbits were randomly assigned to 24-h, 4-day, or 14-day reperfusion groups or a sham group (n = 9 or 10 per group). SCI was induced by occlusion of the infrarenal aorta for 16 min. Hind-limb motor function was assessed using the Tarlov scale (0 = paraplegia, 4 = normal). The gray matter damage was assessed on the basis of the number of normal neurons in the anterior spinal cord. White matter damage was assessed on the basis of the extent of vacuolation and accumulation of amyloid precursor protein immunoreactivity. RESULTS: Tarlov scores gradually decreased and reached a nadir 14 days after reperfusion. There were no significant differences in the number of normal neurons among the 24-h, 4-day, and 14-day groups. The extent of vacuolation, expressed as a percent of total white matter area, was significantly greater in the 4-day and 14-day groups in comparison with the sham group. By contrast, there was no difference in vacuolation between the sham and 24-h groups. Amyloid precursor protein immunoreactivity was greater in the 4-day and 14-day groups. CONCLUSION: The results in the current study show that SCI induced white matter injury as well as gray matter injury in a rabbit model of SCI. The time course for 14 days after reperfusion may differ among the gray and white matter damages and hind-limb motor function in rabbits subjected to SCI.     

Cyclosporin A reduces delayed motor neuron death after spinal cord ischemia in rabbits

BACKGROUND: Spinal cord ischemia has varied etiologies, and in some cases, may develop into paraplegia. This is attributable to the vulnerability of spinal motor neurons to ischemia. We evaluated the potential of the immunosuppressant cyclosporin A for treatment of spinal motor neuron damage caused by ischemia. METHODS: Twenty-eight rabbits were randomized into four groups of 7 animals each: group A (cyclosporin A not administered), group B (2.5 mg/kg cyclosporin A), group C (25 mg/kg cyclosporin A), and group S (sham-operated). The spinal cord ischemia model was created by a 15-minute occlusion of the aorta just caudal to a renal artery with a balloon catheter. Administration of cyclosporin A began 30 minutes after restoration of blood flow. The spinal cords were removed after 7-day monitoring of neurologic function. Pathology specimens were prepared, and after staining them with hematoxylin-eosin, viable motor neurons in the ventral spinal cord were counted under light microscopy. RESULTS: At 7 days after reperfusion, recovery of motor function was seen at varying degrees in groups B and C, whereas all animals in group A continued to exhibit paraplegia. In group C, most of the animals recovered to the baseline level, before creation of the ischemia model. A significant difference in numbers of viable neurons was found in group A (cell count, 10.1 +/- 4.7) and group C (cell count, 22.2 +/- 8.0) (p < 0.05). Higher numbers of viable motor neurons corresponded to a greater recovery of motor function. CONCLUSIONS: These results suggest that cyclosporin A administration is effective against neuronal damage caused by spinal cord ischemia.     

Early ischemic preconditioning without hypotension prevents spinal cord injury caused by descending thoracic aortic occlusion

OBJECTIVE: Postoperative neurologic deficits after thoracic aortic reconstruction vary widely. Our previous study showed that delayed ischemic preconditioning could prevent spinal cord injury caused by occlusion of the descending thoracic aorta in pigs. We investigated early ischemic preconditioning in the same model. METHODS: Twenty-eight pigs were divided into 4 groups: group 1 (n = 6) underwent a sham operation, group 2 (n = 6) underwent aortic occlusion for 20 minutes, group 3 (n = 8) underwent aortic occlusion for 35 minutes, and group 4 (n = 8) underwent aortic occlusion for 20 minutes and underwent aortic occlusion 80 minutes later without hypotension for 35 minutes. Aortic occlusion was accomplished by using 2 balloon occlusion catheters placed fluoroscopically at T6 to T8 above the diaphragm and at the aortic bifurcation. Neurologic evaluation was performed by an independent observer according to the Tarlov scale (0-4). The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin-and-eosin stain. Histologic results (number of neurons and grade of inflammation) were scored (0-4) and were similarly analyzed. Statistical analysis was by means of the Kruskal-Wallis test. RESULTS: Group 4 had a better neurologic outcome at 24, 48, and 120 hours in comparison with group 3 (P <.001). The histologic changes were proportional to the neurologic test scores, with the more severe and extensive gray matter damage in animals of group 3 (number of neurons, P <.001; grade of inflammation, P <.001). CONCLUSION: Early ischemic preconditioning without hypotension protects against spinal cord injury after aortic occlusion, as confirmed by using the Tarlov score and histopathology.     

脊髓缺血再灌注损伤中运动诱发电位的监测作用

目的　探讨运动诱发电位（ＭＥＰ）对脊髓缺血再灌注损伤中神经功能的监测作用。　方法　对２６ 只大鼠腰骶段脊髓缺血前、缺血１５、２５ 、４０ 分钟及再灌注后５、１５、３０ 分钟、１、２ 和２４ 小时ＭＥＰ变化进行监测。　结果　在缺血１５ 分钟时ＭＥＰ潜伏期明显延长（Ｐ＜ ０．０１） ,波幅在缺血２５ 分钟时明显减小（ Ｐ＜ ０－０１） ,缺血４０ 分钟时波形消失;再灌注后５ 分钟时波形恢复,但潜伏期大于正常（Ｐ＜０－０１） ,波幅小于正常（Ｐ＜０－０１）;再灌注后１５ 分钟至２ 小时波幅恢复正常（Ｐ＞ ０－０５）,潜伏期无恢复;再灌注后２４ 小时潜伏期虽然呈恢复趋势,但与再灌注早期相比,差异无显著性意义,此时波幅又明显下降低于正常（Ｐ＜０－０１） ,再灌注后２４ 小时双下肢运动功能比再灌注早明显降低（ Ｐ＜ ０－０５） 。　结论ＭＥＰ能够准确监测脊髓神经功能在缺血再灌注损伤中的变化