缺血预处理对犬脊髓损伤及热休克蛋白70表达影响的研究

目的评价缺血预处理对犬脊髓损伤及热休克蛋白70表达的影响。方法41条杂种犬随机分成假手术组6只、预处理组21只、对照组14只。预处理组主动脉阻断6min后开放6min,反复2次,之后阻断35min;对照组主动脉阻断35min。术后进行神经功能评分,检测脊髓组织中热休克蛋白70表达。结果在再灌注后6h、24h预处理组热休克蛋白70于胞质和胞核均有表达,且强于对照组;而且神经功能评分预处理组高于对照组。在再灌注后7d预处理组神经功能评分无明显改变,且仍见热休克蛋白70表达。结论缺血预处理可以增加脊髓的缺血耐受;热休克蛋白70在胞质和胞核中表达可能在缺血耐受中起到一定的作用。     

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.     

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.     

The influence of dextrose administration on neurologic outcome after temporary spinal cord ischemia in the rabbit

The influence of dextrose administration on neurologic outcome after temporary spinal cord ischemia was examined in New Zealand white rabbits. Spinal cord ischemia was produced by infrarenal balloon occlusion of the aorta in unanesthetized animals. Animals were observed for 3 days for neurologic evaluation. Fasted animals received intravenous dextrose, 0.5 g.kg-1, or placebo before a period spinal cord ischemia. The dextrose was administered as either a bolus of a 50% solution (D50) 15 min before ischemia or as an infusion of a 5% solution (D5W) over 90 min before ischemia. With either mode of administration, preocclusion plasma glucose level was moderately increased as compared with that in animals that received lactated Ringer's solution in equivalent volume, i.e., for the D50 bolus: 291 +/- 82 (SD) versus 166 +/- 67 mg.dl-1 (P less than 0.005); and for D5W infusion: 177 +/- 38 versus 137 +/- 13 mg.dl-1 (P less than 0.01). With either mode of administration, neurologic outcome was poorer (P less than 0.025) at 72 h in the animals that had received dextrose. For example, of the 10 animals that received D5W by infusion, nine were paraplegic (unable to walk) 72 h after ischemia, whereas only three of 10 control animals were paraplegic. The adverse effect of an increased blood glucose level has been demonstrated previously for cerebral ischemia. The present results are the first demonstration that increased plasma glucose may result in a worsened neurologic outcome after spinal cord ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of transcranial motor evoked potentials in predicting neurologic and histopathologic outcome after experimental spinal cord ischemia

BACKGROUND: Monitoring of myogenic motor evoked potentials to transcranial stimulation (tcMEPs) is clinically used to assess motor pathway function during aortic and spinal procedures that carry a risk of spinal cord ischemia (SCI). Although tcMEPs presumably detect SCI before irreversible neuronal deficit occurs, and prolonged reduction of tcMEP signals is thought to be associated with impending spinal cord damage, experimental evidence to support this concept has not been provided. In this study, histopathologic and neurologic outcome was examined in a porcine model of SCI after different durations of intraoperative loss of tcMEP signals. METHODS: In 15 ketamine-sufentanil-anesthetized pigs (weight, 35-45 kg) the spinal cord feeding lumbar arteries were exposed. tcMEP were recorded from the upper and lower limbs. Under normothermic conditions, animals were randomly allocated to undergo short-term tcMEP reduction (group A, < 10 min, n = 5) or prolonged tcMEP reduction (group B, 60 min, n = 10), resulting from temporary or permanent clamping of lumbar segmental arteries. Neurologic function was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated 72 h after induction of SCI. RESULTS: In all animals except one, segmental artery clamping reduced tcMEP to below 25% of baseline. All but one animal in group A had reduced tcMEP for less than 10 min and had normal motor function and no infarction at 72 h after the initial tcMEP reduction. Seven animals in group B (70%) had reduced tcMEP signals for more than 60 min and were paraplegic with massive spinal cord infarction at 72 h. Two animals (one in both groups) had tcMEP loss for 40 min, with moderate infarction and normal function. In general, histopathologic damage and neurologic dysfunction did not occur when tcMEP amplitude recovered within 10 and 40 min after the initial decline, respectively. CONCLUSION: Prolonged reduction of intraoperative tcMEP amplitude is predictive for postoperative neurologic dysfunction, while recovery of the tcMEP signal within 10 min after the initial decline corresponds with normal histopathology and motor function in this experimental model. This finding confirms that intraoperative tcMEPs have a good prognostic value for neurologic outcome during procedures in which the spinal cord is at risk for ischemia.     

Immunophilin ligands FK506 and cyclosporine A improve neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits

BACKGROUND: We comparatively evaluated the protective effect of the immunophilin ligands cyclosporine A (INN: ciclosporin), FK506, and rapamycin on the spinal cord in a rabbit model of transient ischemia. Both cyclosporine A and FK506 inhibit calcineurin, whereas rapamycin does not. METHODS: Thirty-six male New Zealand White rabbits were divided into the following 6 groups: group C, 15 minutes of spinal cord ischemia; group FK, FK506 (1 mg/kg) administered 30 minutes before ischemia; group CsA, cyclosporine A (30 mg/kg) administered 30 minutes before ischemia; group CsA-C, chronic administration of cyclosporine A (20 mg/kg) for 9 days before ischemia; group R, rapamycin (1 mg/kg) administered 30 minutes before ischemia; and group R+FK, rapamycin (1 mg/kg) administered 20 minutes before FK506 pretreatment (1 mg/kg). Group CsA-C was added because the drug does not readily cross the blood-brain barrier. Neurologic function was evaluated by Johnson's 5-point scale at 8, 24, and 48 hours after ischemia, and histopathology was assessed 48 hours after ischemia. RESULTS: At 24 and 48 hours after ischemia, the Johnson score was better in groups FK (4.0 +/- 1.1), R+FK (3 +/- 1.1), and CsA-C (2.7 +/- 1.2) than in group C (0.8 +/- 1.2). Numbers of morphologically intact anterior horn cells were higher in groups FK (31.3 +/- 9.9), R+FK (23.2 +/- 4.5), and CsA-C (18.3 +/- 6.8) than in group C (6.3 +/- 4.3). CONCLUSIONS: FK506 and chronic administration of cyclosporine A, but not rapamycin, protect the spinal cord from transient ischemia. Although these results are compatible with inhibition of calcineurin in the mechanism of neuroprotective action of these drugs, other effects through different pathways cannot be excluded before further study.     

Establishment of a local cooling model against spinal cord ischemia representing prolonged induction of heat shock protein

OBJECTIVES: Paraplegia is one of the serious complications of thoracoabdominal aortic operations. Regional hypothermia protects against spinal cord ischemia although the protective mechanism remains unknown. We attempted to create a simple model of local cooling under transient spinal cord ischemia and evaluated the effect using functional and histologic findings. METHODS: Male domesticated rabbits were divided into 3 groups: control, normothermic group (group N), and local hypothermic group (group H). A balloon catheter was used for spinal cord ischemia by abdominal aortic clamping. A cold pack attached to the lumbar region could lower the regional cord temperature initially. Neurologic function was evaluated by the Johnson score. Cell damage was analyzed by observing motor neurons with the use of hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated deoxy-uracil triphosphate biotin in situ nick end labeling (TUNEL), and immunoreactivity of heat shock protein. RESULTS: Physiologic estimation showed that local hypothermia improved the functional deficits (group N, 1.3 +/- 0.9; group H, 4.9 +/- 0.3; P =.0020). Seven days after reperfusion, there was a significant difference in the motor neuron numbers between groups N and H (group N, 7.2 +/- 1.9; group H, 20.4 +/- 3.2; P =.0090). The number of TUNEL-positive motor neurons was reduced significantly (group N, 7.2 +/- 2.4; group H, 1.0 +/- 0.7; P =.0082). Heat shock protein immunoreactivity was prolonged up to 2 days after reperfusion in the hypothermic group. CONCLUSIONS: These results suggest that local hypothermia extended the production of heat shock protein in spinal cord motor neurons after reperfusion and inhibited their apoptotic change.     

The effects of FK506 on neurologic and histopathologic outcome after transient spinal cord ischemia induced by aortic cross-clamping in rats

Spinal cord injury is a devastating complication of thoracoabdominal aortic surgery. We investigated the effect of the immunosuppressant FK506, a macrolide antibiotic demonstrated to have neuroprotective effects in cerebral ischemia models, in a rat model of transient spinal cord ischemia. Spinal cord ischemia was induced in anesthetized rats by using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation; control, receiving only vehicle; FK506 A, receiving FK506 (1 mg/kg IV) before clamping; and FK506 B, receiving FK506 (1 mg/kg IV) at the onset of reperfusion. Neurologic status was assessed at 24 h and then daily up to 96 h with a 0 to 6 scale (0, normal function; 6, severe paraplegia). Rats were randomly killed at 24, 48, or 96 h, and spinal cords were harvested for histopathology. Physiologic variables did not differ significantly among experimental groups. All control rats suffered severe and definitive paraplegia. FK506-treated rats had significantly better neurologic outcome compared with control. Histopathologic analysis disclosed severe injury in the lumbar gray matter of all control rats, whereas most FK506-treated rats had less injury. These data suggest that FK506 can improve neurologic recovery and attenuate spinal cord injury induced by transient thoracic aortic cross-clamping. IMPLICATIONS: A single dose-injection of the immunosuppressant FK506 significantly improved neurologic outcome and attenuated spinal cord injury induced by transient thoracic aortic cross-clamping in the rat.     

The effects of N(G)-nitro-L-arginine-methyl ester on neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits.

Little is known about the role of nitric oxide in the pathophysiology of spinal cord ischemia. We evaluated the effects of nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine-methyl ester (L-NAME) in rabbits whose abdominal aorta was occluded for 20 min (Experiment 1) or 25 min (Experiment 2). In Experiment 1, the L-NAME group (n = 6) received 3 mg/kg i.v. L-NAME, followed by an i.v. infusion of 3 mg x kg(-1). h(-1) until 6 h after reperfusion. Ischemia was induced 20 min after the start of L-NAME. The phenylephrine group (n = 6) received phenylephrine to maintain comparable blood pressure. The control group (n = 6) received saline. In Experiment 2, L-NAME (3 mg/kg i.v. L-NAME, followed by an i.v. infusion of 3 mg x kg(-1). h(-1) until 6 h after reperfusion) and phenylephrine groups (n = 6 each) were studied. Ischemia was induced 100 min after the start of L-NAME. Forty-eight hours after reperfusion, hindlimb motor function and histopathology of the spinal cord were examined. In Experiment 1, L-NAME and phenylephrine both improved neurologic outcome, with higher intraischemic blood pressures than saline. In Experiment 2, L-NAME worsened the neurologic and histopathologic outcome compared with phenylephrine. Attenuation of damage by L-NAME in Experiment 1 may be attributable to an intraischemic blood pressure increase. The worse outcome with L-NAME in Experiment 2 suggests that NOS inhibition exacerbates ischemic spinal cord damage. IMPLICATIONS: Nonselective inhibition of nitric oxide synthase activity has aggravating effects on the neurologic and histopathologic outcome after transient spinal cord ischemia.     

Delayed pharmacological pre-conditioning effect of mitochondrial ATP-sensitive potassium channel opener on neurologic injury in a rabbit model of spinal cord ischemia

Background: Diazoxide, pharmacological openers of mitochondrial ATP-sensitive potassium channels have been shown to induce early pre-conditioning in the spinal cord. Here, the authors investigated whether diazoxide also induce delayed pre-conditioning and thereby reduce neurologic complications using a rabbit model of spinal cord ischemia.
Methods: Infrarenal blood flow was interrupted for 20 min in 21 rabbits. Non-treated control animals received no pre-treatment. Diazoxide (5 mg/kg) were given 48 h before 20 min ischemia in the 48-h DZ group, whereas 15-min DZ group received diazoxide (5 mg/kg) 15 min before 20-min ischemia. Neurological functions were evaluated using Johnson scores for 3 days after reperfusion, after which, spinal cords were procured for hematoxylin and eosin staining for cell counting.
Results: Johnson scores revealed a marked improvement in both the diazoxide-treated groups vs. the non-treated control group at 3, 24, 48, and 72 h after reperfusion ( P <0.01). The histologic changes were proportional to the Johnson scores, with better preservation of motor neuron numbers in the animals of the 48-h DZ and 15-min DZ group relative to the non-treated controls (81±12, 90±10, 50±23 motor neurons, respectively, P <0.01). No difference was found between the 48-h DZ group and 15-min DZ group with respect to the Johnson scores or neuron numbers.
Conclusions: The study demonstrates that pre-treatment with diazoxide 48 h before ischemia, induce delayed pharmacological pre-conditioning, thereby significantly improving clinical neurologic scores and histologic findings in this animal model.     

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.     

Enhancement of heat shock protein expression after transient ischemia in the preconditioned spinal cord of rabbits

Purpose: This investigation was designed to evaluate the mechanism used to acquire a tolerance to spinal ischemia. We investigated inductions of the heat shock protein (HSP) 70 gene and protein in rabbit spinal cord with or without preconditioning. Methods: Neurologic function, morphologic changes, and inductions of HSP70 messenger RNA (mRNA) and protein were compared in the cases of a 15-minute ischemia 2 days after sham treatment and a 15-minute ischemia 2 days after 10-minute preconditioning. Result: HSP70 mRNA was induced at 8 hours of reperfusion after a 15-minute ischemia 2 days after sham treatment. HSP70 protein was induced slightly in selective motor neuron cells at 8 hours of reperfusion, and about 70% of motor neuron cells showed selective cell death after 7 days of reperfusion (p < 0.01). On the other hand, large populations of the motor neuron cells survived at 7 days after the 15-minute ischemia that was applied at 2 days after preconditioning (p < 0.01). HSP70 mRNA was induced persistently as compared with the case of a 15-minute ischemia 2 days after sham treatment. The motor neuron cells strongly produced immunoreactive HSP70 from 8 hours to 2 days. Conclusion: Preconditioning with 10-minute ischemia enhanced and prolonged the HSP70 gene expression at both mRNA and protein levels and saved the motor neuron cells from subsequent lethal ischemia. These changes of HSP70 gene expression may play an important role in the acquisition of ischemic tolerance of motor neuron cells in rabbit spinal cord. (J Vasc Surg 1998;27:720-5.)     

Transcranial myogenic motor-evoked potentials after transient spinal cord ischemia predicts neurologic outcome in rabbits

OBJECTIVE: Myogenic transcranial motor-evoked potentials (tc-MEPs) were applied to monitor spinal cord ischemia in the repairs of thoracoabdominal aortic aneurysms. We investigated whether tc-MEPs after spinal cord ischemia/reperfusion could be used to predict neurologic outcome in leporine model. METHODS: Tc-MEPs were measured at 30-second intervals before, during, and after spinal cord ischemia (SCI) induced by balloon occlusion of the infrarenal aorta. Twenty rabbits were divided into five groups. Four groups (n = 4 animals in each group) had transient ischemia induced for 10, 15, 20, or 30 minutes. In fifth group, the terminal aorta at the aortic bifurcation was occluded for 30 minutes. All animals were evaluated neurologically 48 hours later, and their spinal cords were removed for histologic examination. RESULTS: The tc-MEPs in each SCI group rapidly disappeared after SCI. After reperfusion, the recovery of tc-MEPs amplitude was inversely correlated to duration of SCI. Tc-MEPs amplitude at one hour after reperfusion was correlated with both neurologic score and number of neuron cells in the spinal cord 48 hours later. Logistic regression analysis demonstrated that the neurologic deficits differed significantly between animals with tc-MEPs amplitude of less than 75% of the baseline and those with an amplitude of more than 75%. CONCLUSIONS: The amplitude of tc-MEPs after ischemia /reperfusion of the spinal cord showed a high correlation with durations of SCI, with neurologic deficits, and with pathologic findings of the spinal cord. Tc-MEPs, therefore, could be used to predict neurologic outcome. In particular, tc-MEPs whose amplitude recovered by less than 75% indicated a risk of paraplegia.     

苦参素对大鼠急性脊髓损伤后热休克蛋白47表达的影响

目的探讨苦参素治疗大鼠急性脊髓损伤(SCI)的机制。方法用30只Wistar大鼠制作钳夹型SCI模型,随机分成正常组、假手术组、SCI组、对照组和治疗组,在SCI后3d及每周评价BBB评分,并在第8周用免疫组化方法分析脊髓中热休克蛋白47(HSP47)的表达情况。结果正常组和假手术组Wistar大鼠脊髓组织低表达胶质细胞酸性蛋白(GFAP)和HSP47,高表达神经丝蛋白(NF),在SCI后GFAP和HSP47表达明显提高(P<0.05),NF表达明显降低(P<0.05)。苦参素治疗后,GFAP和HSP47表达降低(P<0.05),NF表达升高(P<0.05)。结论苦参素对Wistar大鼠SCI具有治疗作用,很可能通过抑制HSP47的表达发挥治疗作用。     

The time course of acquisition of ischemic tolerance and induction of heat shock protein 70 after a brief period of ischemia in the spinal cord in rabbits

We examined the time course of development of ischemic tolerance in the spinal cord and sought its mechanism exploring the expression of heat shock protein 70 (HSP70). Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta. In Experiment 1, neurologic and histopathologic outcome was evaluated 48 h after prolonged ischemia (20 min) that was given 2 days, 4 days, or 7 days after a short period of ischemia (ischemic pretreatment) sufficient to abolish postsynaptic component of spinal cord evoked potentials. Control animals were given prolonged ischemia 4 days after sham operation. In Experiment 2, HSP70 expression in motor neurons after pretreatment without exposure to prolonged ischemia was examined by immunohistochemical staining. Ischemic pretreatment 4 days (but not 2 days or 7 days) before 20 min ischemia exhibited protective effects against spinal cord injury. In the cytoplasm, HSP70 immunoreactivity was mildly increased after 2, 4, and 7 days of ischemic pretreatment. However, the incidence of nuclear HSP70 immunoreactivity 2 days, 4 days, and 7 days after ischemic pretreatment was 2 of 6 animals, 4 of 6 animals, and 1 of 6 animals, respectively (none in the control group). These results suggest that ischemic tolerance is apparent 4 days after ischemic pretreatment and that HSP70 immunoreactivity in the nucleus may provide some insight into the mechanisms of ischemic tolerance in the spinal cord.     

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model

STUDY DESIGN: Randomized study. OBJECTIVES: To evaluate the effects of thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-alpha production. SETTING: Animal experimental laboratory, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea. METHODS: Spinal cord ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in group N did not undergo ischemic insult, but rabbits in groups C (the untreated group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of reperfusion, rabbits were killed for histopathologic examination and Western blot analysis of TNF-alpha. RESULTS: The THA and THB groups showed significantly less neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion. The number of normal spinal motor neurons in ventral gray matter was higher in THA and THB than in C, but no difference was observed between THA and THB. Western blot analysis showed a significantly higher level of TNF-alpha in C than in THA and THB at 1.5 h of reperfusion, but no difference was observed between C, THA, or THB at 3 or 5 days of reperfusion. CONCLUSION: Thalidomide treatment before ischemic insult reduces early phase ischemia/reperfusion injury of the spinal cord in rabbits.     

Adenosine A2A analogue improves neurologic outcome after spinal cord trauma in the rabbit

BACKGROUND: ATL-146e, an adenosine A2A agonist, reduces paralysis after spinal cord ischemia-reperfusion. We hypothesized that systemic ATL-146e could improve neurologic outcome after blunt spinal cord trauma. METHODS: Twenty rabbits survived a thoracic spinal cord impact of 30 g-cm. One group received 0.06 microg/kg/min ATL-146e for the first 3 hours after impact (A2A group), whereas a second group received saline carrier (T/C group). Neurologic outcome was measured using the Tarlov scale (0-5). Histologic sections from the A2A and T/C groups were compared for neuronal viability. RESULTS: There was significant improvement in Tarlov scores of A2A animals compared with T/C animals at 12 hours (p = 0.007), with a trend toward improvement at 36 (p = 0.08) and 48 (p = 0.09) hours after injury. There was decreased neuronal attrition in A2A animals (p = 0.06). CONCLUSION: Systemic ATL-146e given after spinal cord trauma results in improved neurologic outcome. Adenosine A2A agonists may hold promise as a rapidly acting alternative to steroids in the early treatment of the spinal cord injured patient.     

A histopathologic study of spinal cord ischemia using an isohistogenic rat upper-half-body transplantation model

To study the histopathologic changes of spinal cords exposed to long-duration complete ischemia, the authors developed an upper-half-body transplantation model of inbred rat. In this model, an infant Lewis rat is transplanted to the inguinal region of another adult Lewis rat using microsurgical vascular anastomosis. Even when 2-week-old donor rats were exposed to complete ischemia for 90 minutes, functions of the spinal cord were comparatively preserved. In histopathologic observations, degeneration proportional to complete ischemia duration was noted. In the 60-minute ischemia group of 2-week-old donor rats, however, no substantial differences from normal spinal cord were observed. Under conditions of equal ischemia duration, it appeared the younger animal had the greater ischemic tolerance.