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.     

Continuous Monitoring of Cerebrospinal Fluid Oxygen Tension in Relation to Motor Evoked Potentials during Spinal Cord Ischemia in Pigs

Background: Perioperative assessment of spinal cord oxygenation might guide measures to prevent neurologic deficits secondary to ischemic or traumatic damage of the spinal cord. Although cerebrospinal fluid (CSF) partial pressure of oxygen (Po2) measurement has been used to detect spinal cord ischemia (SCI), the diagnostic value and the temporal resolution of CSF Po2 measurement compared with functional assessment of the spinal cord is unknown. This study compared CSF Po2 with transcranial motor evoked potentials (tcMEPs) for detection of experimental SCI.

Methods: The aorta and segmental arteries were exposed in 10 sufentanil-ketamine-anesthetized pigs (weight, 40-50 kg). Myogenic tcMEPs were recorded from the upper and lower limbs, and continuous assessment of CSF Po2 was provided by two Clark-type microcatheters inserted in the lumbar and thoracic intrathecal space. Graded lumbar SCI was produced by sequential clamping of segmental arteries. The relation between CSF Po2 and tcMEP during graded SCI was determined using linear regression. Diagnostic characteristics of CSF Po2 values for clinical SCI were determined using different cutoff points of CSF Po2.

Results: Lumbar CSF Po2 (baseline, 44 [interquartile range, 38-54] mmHg) decreased below 50% in all animals and was linearly related to loss of tcMEP amplitude in all animals. The median lumbar CSF Po2 during reduction of tcMEP to less than 25% of baseline was 11 (4-29) mmHg, whereas thoracic CSF Po2 remained constant (40 [28-50] mmHg). During absence of the tcMEP signal, lumbar CSF Po2 was less than 20 mmHg in 80% of the animals. Optimal sensitivity and predictive values of CSF Po2 measurement for SCI were in the range of 40-60% of baseline.     

Continuous monitoring of cerebrospinal fluid oxygen tension in relation to motor evoked potentials during spinal cord ischemia in pigs

BACKGROUND: Perioperative assessment of spinal cord oxygenation might guide measures to prevent neurologic deficits secondary to ischemic or traumatic damage of the spinal cord. Although cerebrospinal fluid (CSF) partial pressure of oxygen (Po2) measurement has been used to detect spinal cord ischemia (SCI), the diagnostic value and the temporal resolution of CSF Po2 measurement compared with functional assessment of the spinal cord is unknown. This study compared CSF Po2 with transcranial motor evoked potentials (tcMEPs) for detection of experimental SCI. METHODS: The aorta and segmental arteries were exposed in 10 sufentanil-ketamine-anesthetized pigs (weight, 40-50 kg). Myogenic tcMEPs were recorded from the upper and lower limbs, and continuous assessment of CSF Po2 was provided by two Clark-type microcatheters inserted in the lumbar and thoracic intrathecal space. Graded lumbar SCI was produced by sequential clamping of segmental arteries. The relation between CSF Po2 and tcMEP during graded SCI was determined using linear regression. Diagnostic characteristics of CSF Po2 values for clinical SCI were determined using different cutoff points of CSF Po2. RESULTS: Lumbar CSF Po2 (baseline, 44 [interquartile range, 38-54] mmHg) decreased below 50% in all animals and was linearly related to loss of tcMEP amplitude in all animals. The median lumbar CSF Po2 during reduction of tcMEP to less than 25% of baseline was 11 (4-29) mmHg, whereas thoracic CSF Po2 remained constant (40 [28-50] mmHg). During absence of the tcMEP signal, lumbar CSF Po2 was less than 20 mmHg in 80% of the animals. Optimal sensitivity and predictive values of CSF Po2 measurement for SCI were in the range of 40-60% of baseline. CONCLUSIONS: The data indicate that intrathecal Po2 measurement is a sensitive monitoring technique to track real-time changes in local spinal cord oxygenation. Continuous monitoring of CSF Po2 might be applied for evaluation of patients who are at risk for direct or secondary SCI.     

Thoracoabdominal Aortic Aneurysm Repair: Interplay of Spinal Cord Protecting Modalities

BACKGROUND: The purpose of this study was to assess the complementary use of different methods of measuring spinal cord perfusion during thoracoabdominal aortic surgery. METHODS: The spinal cords of 28 patients undergoing surgery on the thoracoabdominal aorta were monitored with transcranial electrical stimulation (tcMEP) and somatosensory-evoked potentials (SSEP). Available approaches of spinal cord-protection included: Moderate systemic hypothermia, constant cerebrospinal fluid (CSF) drainage and pressure monitoring, reimplantation of segmental arteries, cardiopulmonary bypass (CPB), and staged clamping. RESULTS: Fourteen of 19 patients (75%) undergoing open surgical treatment (Group I) exhibited loss of tcMEP after proximal aortic clamping. In nine cases (47%), we observed recovery of tcMEP after intraoperative interventions, while two patients subsequently developed paraplegia and three died. Seventeen of 19 patients showed loss of SSEP, with recovery in 12 cases (63%). During stent-graft implantation (Group II), one of nine patients (11%) demonstrated tcMEP loss with intraoperative, intervention-related recovery. The SSEP-recording course remained stable. CONCLUSIONS: tcMEP/SSEP monitoring has proved to be an excellent means of detecting spinal cord ischaemia during surgery on thoracoabdominal aortic aneurysms. The prognostic value of tcMEP monitoring should be considered superior to that of SSEP measurements, because of its direct and rapid response to spinal malperfusion. Through combined neurophysiological monitoring, vital parameter balancing and intraoperative interventions, spinal cord perfusion improves and recovery of tcMEP and SSEP is achievable, reducing the prevalence of postoperative paraplegia.     

A Novel Canine Model of Spinal Cord Ischemia with Reproducible Neurologic Outcomes

Purpose To develop a canine model of spinal cord ischemia (SCI) with highly reproducible neurologic outcomes.Methods Spinal cord ischemia was induced by cross-clamping the proximal descending aorta. To produce substantial ischemia in the critical lumbar region, the proximal aortic blood pressure (PAP) was reduced to 80 mmHg by withdrawing blood into a reservoir connected to the left subclavian artery. We conducted an intraischemia spinal cord electrophysiologic study and a postischemia assessment of hindlimb motor function in six animals subjected to this procedure with an aortic occlusion time of 40 min, and in six animals subjected only to aortic occlusion for 60 min.Results All the animals subjected to this procedure exhibited a significant decrease in motor-evoked spinal cord potentials to transcranial electric stimulation (MEPs) during the acute ischemic phase, and they were paraplegic 48 h after ischemia. In contrast, two of the animals not subjected to PAP reduction showed complete functional recovery with intact MEP findings.Conclusion This model is feasible for experimental SCI studies because it can reliably and easily reproduce substantial ischemia.     

Isoflurane produces delayed preconditioning against spinal cord ischemic injury via release of free radicals in rabbits

BACKGROUND: Whether isoflurane preconditioning produces delayed neuroprotection in the spinal cord is unclear. The authors tested the hypothesis that isoflurane produces delayed preconditioning against spinal cord ischemic injury and, further, that the beneficial effect is dependent on free radicals. METHODS: In experiment 1, 63 rabbits were randomly assigned to seven groups (n = 9 each): Animals in the control group only underwent spinal cord ischemia without pretreatment; animals in the Iso24h, Iso48h, and Iso72h groups received 40 min of 1.0 minimum alveolar concentration isoflurane in 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia; animals in the O2 24h, O2 48h, and O2 72h groups received 40 min of 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia. In experiment 2, 48 rabbits were randomly assigned into four groups (n = 12 each): Animals in the O2 and Iso groups received 3 ml/kg saline intraperitoneally 1 h before each session of oxygen pretreatment and isoflurane pretreatment, respectively. In the DMTU+Iso and DMTU+O2 groups, 10% dimethylthiourea (DMTU, a potent free radical scavenger) dissolved in saline (3 ml/kg) was administered at the same time point. Twenty-four hours after the last pretreatment, animals were subjected to spinal cord ischemia. Spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, neurologic function and histopathology of the spinal cord were examined. RESULTS: In experiment 1, the neurologic and histopathologic outcomes in the Iso24h and Iso48h groups were better than those in the control group (P < 0.005 for each comparison); the neurologic and histopathologic outcomes in the control group showed no significant differences in comparison with the O2 24h, O2 48h, O2 72h, and Iso72h groups (P > 0.05 for each comparison). In experiment 2, the neurologic and histopathologic outcomes in the Iso group were better than those in the DMTU+Iso, O2, and DMTU+O2 groups (P < 0.01 for each comparison); there were no significant differences in the neurologic and histopathologic outcomes among the DMTU+Iso, O2, and DMTU+O2 groups (P > 0.05 for each comparison). CONCLUSIONS: Isoflurane produces delayed preconditioning against spinal cord ischemic injury, and the beneficial effect may be dependent on the release of free radicals.     

Isoflurane Produces Delayed Preconditioning against Spinal Cord Ischemic Injury via Release of Free Radicals in Rabbits

Background: Whether isoflurane preconditioning produces delayed neuroprotection in the spinal cord is unclear. The authors tested the hypothesis that isoflurane produces delayed preconditioning against spinal cord ischemic injury and, further, that the beneficial effect is dependent on free radicals.

Methods: In experiment 1, 63 rabbits were randomly assigned to seven groups (n = 9 each): Animals in the control group only underwent spinal cord ischemia without pretreatment; animals in the Iso24h, Iso48h, and Iso72h groups received 40 min of 1.0 minimum alveolar concentration isoflurane in 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia; animals in the O224h, O248h, and O272h groups received 40 min of 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia. In experiment 2, 48 rabbits were randomly assigned into four groups (n = 12 each): Animals in the O2 and Iso groups received 3 ml/kg saline intraperitoneally 1 h before each session of oxygen pretreatment and isoflurane pretreatment, respectively. In the DMTU+Iso and DMTU+O2 groups, 10% dimethylthiourea (DMTU, a potent free radical scavenger) dissolved in saline (3 ml/kg) was administered at the same time point. Twenty-four hours after the last pretreatment, animals were subjected to spinal cord ischemia. Spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, neurologic function and histopathology of the spinal cord were examined.

Results: In experiment 1, the neurologic and histopathologic outcomes in the Iso24h and Iso48h groups were better than those in the control group (P < 0.005 for each comparison); the neurologic and histopathologic outcomes in the control group showed no significant differences in comparison with the O224h, O248h, O272h, and Iso72h groups (P > 0.05 for each comparison). In experiment 2, the neurologic and histopathologic outcomes in the Iso group were better than those in the DMTU+Iso, O2, and DMTU+O2 groups (P < 0.01 for each comparison); there were no significant differences in the neurologic and histopathologic outcomes among the DMTU+Iso, O2, and DMTU+O2 groups (P > 0.05 for each comparison).     

脊髓损伤后早期减压对诱发电位影响的实验研究

[目的]观察脊髓损伤后早期减压对体感诱发电位及经颅磁刺激运动诱发电位的影响，以探讨诱发电位在判断手术时机及预后中的应用价值。[方法]日本大耳兔32只随机分4组。A组为对照组，不造成脊髓损伤。B、C、D组为脊髓损伤组。对每组动物于不同时间分别检测SEP、MEP。分析波形的潜伏期、峰问波幅。用后肢的Tarlov分级法作伤后运动功能评分。取脊髓标本，行组织学观察。[结果]随着脊髓压迫时间的延长，SEP、MEP的潜伏期逐渐延长，波幅逐渐减小．波幅变化较潜伏期更为敏感。在恢复过程中，脊髓受压时间越短，诱发电位恢复越早。潜伏期恢复早于波幅，而且SEP恢复早于MEP，MEP的恢复早于功能评分。[结论]SEP与TMS-MEP对脊髓损伤十分敏感，能较早反映脊髓损伤程度，可用于指导临床手术治疗和判断预后。     

The relationship between evoked potentials and measurements of S-100 protein in cerebrospinal fluid during and after thoracoabdominal aortic aneurysm surgery.

OBJECTIVE: This study was performed to correlate the changes in concentration of S-100 protein in the cerebrospinal fluid (CSF) during and after thoracoabdominal aortic aneurysm (TAAA) surgery with the results of somatosensory and motor evoked potential monitoring. METHODS: The study was designed as a prospective study at St Antonius Hospital in Nieuwegein, The Netherlands. The participants were 19 patients who were undergoing elective TAAA surgery. CSF samples for analysis of S-100 protein were drawn after the induction of anesthesia, during the cross-clamp period of the critical aortic segment, after 5 minutes of reperfusion of this segment, during the closure of the skin, and 24 hours after the closure of the skin. In all the patients, continuous intraoperative recording of myogenic motor potentials evoked by transcranial electrical stimulation (tcMEP) and somatosensory potentials evoked by stimulation of the posterior tibial nerve took place to monitor the integrity of the spinal cord. The operative technique consisted of staged or sequential clamping to maximize the beneficial effect of the distal perfusion by the left heart bypass, continuous CSF drainage to keep the CSF pressure below 10 mm Hg, and moderate hypothermia (32 degrees C rectal temperature). We correlated the measured concentrations of S-100 protein in CSF with the results of evoked potential monitoring during surgery and the number of intercostals reimplanted and oversewn. RESULTS: In all the patients, the concentration of S-100 protein was increased in CSF. The highest concentration of S-100 protein was found in the CSF sample taken 5 minutes after reperfusion of the critical aortic segment. There was a good (negative) correlation between the changes in S-100 protein in CSF and the changes in motor evoked potential monitoring during the cross-clamp period. The best (negative) correlation was detected between the S-100 protein elevation in the CSF sample drawn 5 minutes after reperfusion and the tcMEP amplitude reduction during clamping (r = -0.73; P =.007). No relation was found between the S-100 protein dynamics in CSF and somatosensory evoked potential monitoring. A positive (r = 0.58; P =.05) correlation was found between the change in tcMEP amplitude during clamping and the number of reattached intercostals. A moderate to good (r = -0.5 to -0.7; P <.05) correlation between the number of reattached intercostals and the changes in S-100 protein concentration in CSF during TAAA surgery was found. Our data show that transient elevations in S-100 protein after cross clamping are larger in those patients with marked decrease in tcMEP from baseline during the cross-clamp period. CONCLUSION: A correlation is shown between an increasing concentration of S-100 protein in CSF and a reduction in tcMEP amplitude during cross clamping of the aorta. The S-100 protein in CSF seems to be a marker of potential clinical value in the evaluation of the effects of procedures to detect and reduce spinal cord ischemia.     

Thoracic and thoracoabdominal aortic aneurysm repair: Use of evoked potential monitoring in 118 patients

PURPOSE: Paraplegia is the most dreaded and severe complication of surgery on the descending thoracic aorta (TAA) and thoracoabdominal aorta (TAAA). The functional integrity of the spinal cord can be monitored by means of intraoperative recording of myogenic-evoked responses after transcranial electrical stimulation (tcMEP) and somatosensory-evoked potential (SEP) monitoring. In this study, we evaluated the results of evoked potential monitoring and the adequacy of the strategy followed. METHOD: The spinal cord of 118 patients (78 men; age, 65 +/- 12 years; 79 TAAAs, 39 TAAs) undergoing surgery on the TAA or TAAA was monitored with tcMEP and SEP. Spinal cord protection was achieved by means of a multimodality approach: moderate hypothermia (32 degrees C rectal temperature), continuous cerebrospinal fluid drainage to keep the pressure less than 10 mm Hg, reimplantation of intercostal arteries, left ventricular bypass grafting, and staged clamping. In the case of evoked potential changes more than 50% of baseline, the strategy was adjusted: reattachment of more segmental arteries when technically feasible, higher distal and proximal perfusion pressures, and enhanced cerebrospinal fluid drainage. RESULTS: Forty-two of 118 patients (35.6%) had a more than 50% of baseline tcMEP reduction during cross-clamping. At this point, only 5 of those 42 cases were also associated with SEP reduction of more than 50% of baseline. On the basis of the tcMEP findings, the strategy was adjusted. Five patients had postoperative paraplegia (4.2%). CONCLUSION: tcMEP monitoring seems to be a useful adjunct of the protective techniques and may cause substantial adjustments in strategy, reducing the incidence of postoperative paraplegia.     

Reduction of ischemic spinal cord injury by dextrorphan: comparison of several methods of administration.

OBJECTIVES: We investigated the effect of dextrorphan, an N -methyl-D -aspartate receptor antagonist, on the reduction of ischemic spinal cord injury and the safe clamping time after various methods of administration. METHODS: Spinal cord ischemia was induced in New Zealand White rabbits by infrarenal aortic clamping and animals were divided into 5 groups. Group A (n = 15) received simple clamping. Groups B (n = 20) and C (n = 35) received dextrorphan pretreatment (10 mg/kg), followed by continuous intravenous or intra-aortic infusion (1 mg/min), respectively. Group D (n = 25) received the same dextrorphan pretreatment and bolus intra-aortic injection at clamping (1 mg per minute of clamping time). Group E (n = 15) received bolus intrathecal injection of dextrorphan (0.2 mg/kg). Each dextrorphan-treated group had a small group of control animals (n = 5). The neurologic status was assessed by the Johnson score (5 = normal, 0 = paraplegic) 48 hours after unclamping, and animals were put to death for histopathologic examination. RESULTS: All dextrorphan-treated groups showed better neurologic function than the respective control animals (P <.001 vs groups B, C, and D; P =.014 vs group E). The order of efficacy of dextrorphan (as revealed by the average of neurologic status) was as follows: group C > group D (P =.017, after 50 minutes of clamping), group D > group B (P =.014, after 45 minutes of clamping), and group B > group E (P <.001, after 40 minutes of clamping). Histopathologic findings did not necessarily correspond with hind-limb neurologic function. CONCLUSIONS: Dextrorphan reduced the physical findings associated with ischemic spinal cord injury, and continuous intra-aortic infusion prolonged the safe clamping time significantly more than delivery by other routes.     

缺血预处理对脊髓缺血损伤细胞内Ca2+变化的影响

目的　观察缺血预处理对脊髓缺血损伤细胞内 Ca2 变化的影响。　方法　将 44只健康新西兰大白兔随机分为三组 :缺血组 2 0只 ,缺血预处理组 2 0只 ,假手术组 4只。缺血组于左肾动脉下夹闭腹主动脉 40分钟后开放灌注 ;缺血预处理组夹闭腹主动脉 5分钟 ,开放 15分钟 ,再次夹闭 40分钟后开放再灌注 ;假手术组动物手术操作同缺血组 ,但不夹闭腹主动脉。分别于夹闭 40分钟后即刻、开放再灌注 2小时、8小时、2 4小时和 72小时各时相点测定脊髓组织 Ca2 含量 ,并评定、记录动物后肢神经功能。　结果　缺血预处理组脊髓组织 Ca2 显著低于缺血组各时相值 ;再灌注 8小时后神经功能评分缺血预处理组明显高于缺血组 (P<0 .0 1)。　结论　缺血预处理具有降低神经元胞浆游离 Ca2 浓度 ,防止Ca2 超载 ,稳定细胞内环境的能力 ,对主动脉阻断所致的脊髓缺血损伤有良好的保护作用。其表现为明显降低瘫痪发生率 ,增加术后神经评分     

Aprotinin reduces injury of the spinal cord in transient ischemia

Objective: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: New Zealand white rabbits (36) of both sexes. Methods: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30 000 KIU as a short intravenous injection after anesthesia, and was followed by 10 000 KIU/h by continuous infusion in group 1 (n=12). Similar volume of saline solution was used in control group of animals (group 2, n=12). Group 3 of animals (sham group, n=12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. Results: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53±7% of the baseline in all ischemic animals. This was followed by a gradual return to 89±8 and 81±13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P>0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P<0.05). Histological observations were clearly correlated with the neurological findings. Conclusion: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.     

Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries

OBJECTIVE: Spinal cord blood flow (SCBF) after sacrifice of thoracoabdominal aortic segmental arteries (TAASA) during thoracoabdominal aortic aneurysm (TAAA) repair remains poorly understood. This study explored SCBF for 72 h after sacrifice of all TAASA. METHODS: Fourteen juvenile Yorkshire pigs underwent complete serial TAASA sacrifice (T4-L5). Six control pigs underwent anesthesia and cooling to 32 degrees C with no TAASA sacrifice. In the experimental animals, spinal cord function was continuously monitored using motor evoked potentials (MEPs) until 1h after clamping the last TAASA. Fluorescent microspheres enabled segmental measurement of SCBF along the entire spinal cord before, and 5 min, 1 h, 5 h, 24 h and 72 h after complete TAASA sacrifice. A modified Tarlov score was obtained for 3 days after surgery. RESULTS: All the pigs with complete TAASA sacrifice retained normal cord function (MEP) until 1h after TAASA ligation. Seven pigs (50%) with complete TAASA sacrifice recovered after 72 h; seven pigs suffered paraparesis or paraplegia. Intraoperatively, and until 1h postoperatively, SCBF was similar among the three groups along the entire cord. Postoperatively, SCBF did not decrease in any group, but significant hyperemia occurred at 5h in controls and recovery animals, but did not occur in pigs that developed paraparesis or paraplegia in the T8-L2 segments (p=0.0002) and L3-S segments (p=0.0007). At 24h, SCBF remained marginally lower from T8 caudally; at 72h, SCBF was similar among all groups along the entire cord. SCBF in the segments T8-L2 at 5h predicted functional recovery (p=0.003). CONCLUSIONS: This study suggests that critical spinal cord ischemia after complete TAASA sacrifice does not occur immediately (intraoperatively), but is delayed 1-5h or longer after clamping, and represents failure to mount a hyperemic response to rewarming and awakening. The short duration of low SCBF associated with spinal cord injury suggests that hemodynamic and metabolic manipulation lasting only 24-72 h may allow routine preservation of normal cord function despite sacrifice of all TAASA secondary to surgical or endovascular repair of large TAAA.     

Direct noninvasive monitoring of spinal cord motor function during thoracic aortic occlusion: use of motor evoked potentials

Spinal cord monitoring during thoracic aneurysmectomy by somatosensory evoked potentials has been criticized for its failure to measure anterior (motor) spinal cord function. We have developed a clinically applicable, noninvasive technique for intraoperative monitoring of motor evoked potentials (MEP), which allows direct functional assessment of spinal cord motor tracts during thoracic aortic occlusion. Twelve dogs underwent continuous intraoperative monitoring of MEP before, during, and after thoracic aortic cross-clamping. Motor tract response to noninvasive cord stimulation (5 to 10 mA, 0.02 msec, 4.3 H2) was recorded by subcutaneous electrodes placed along the length of the spine (T-10, L-1, and L-4). Six animals (group I) subjected to aortic cross-clamping alone demonstrated a characteristic time- and level-dependent deterioration and loss of MEP. Ischemic cord dysfunction (as determined by time from clamping to loss of MEP) progressed from the distal to the proximal cord (L-4 = 11.3 +/- 1.5 minutes; L-1 = 14.9 +/- 2.3 minutes; T-10 = 16.9 +/- 2.3 minutes; p less than 0.05 between all levels). Reperfusion of the distal aorta 20 minutes after clamping resulted in MEP return that progressed from the proximal (T-10) to distal (L-1 and L-4) cord. In another six animals (group II), distal perfusion (mean blood pressure = 95 mm Hg) was maintained for 1 hour after cross-clamping by left atrial-femoral artery bypass. Normal configuration and amplitude of MEP was maintained throughout the cross-clamping period. These data suggest that distinctive changes in MEP indicative of reversible ischemia of spinal cord motor tracts occur after aortic cross-clamping. Such ischemia begins in the most distal cord, exhibits upward progression with time, and can be prevented by maintenance of adequate distal aortic perfusion. Clinical use of MEP monitoring during thoracic aneurysmectomy may provide a method for intraoperative assessment of the adequacy of motor tract perfusion.     

Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury

STUDY DESIGN: A basic study using a spinal cord injury (SCI) model in rats. OBJECTIVES: The effect of mild hypothermic treatment on histological changes and motor function after a rat spinal cord compression injury was assessed. METHODS: Mild spinal cord compression was performed at the eleventh thoracic vertebral level by a 20 g weight for 20 min. Rats in the mild hypothermic model were kept at a body temperature of 33 degrees C and rats in the normothermic group were kept at 37 degrees C for 1 h from beginning of compression. Motor function was evaluated by measuring the frequency of standing. Microglia were stained by isolectin B4 and observed in the compressed portion of the spinal cord. The amount of tumor necrosis factor-alpha (TNF-alpha) in the compressed spinal cord was measured by the ELISA method. RESULTS: In the normothermic rats, microglia proliferated up to 72 h after the compression. Proliferation was substantially inhibited at 48 and 72 h after compression in the hypothermic rats. The motor function of the hypothermic rats improved at 48 and 72 h after the compression, whereas no improvement was seen in the normothermic rats. The amount of TNF-alpha in the compressed portion of the spinal cord was lower in hypothermic rats compared with normothermic rats throughout the experiment. CONCLUSIONS: These results suggest that hypothermic treatment is effective for the amelioration of delayed motor dysfunction via inhibition of microglial inflammatory responses.     

The long-term effects of pre-treatment with activated protein C in a rat model of compression-induced spinal cord injury

OBJECTIVES: Recently, we demonstrated that activated protein C (APC) can lessen the severity of spinal cord injury (SCI) in rats during the acute and subacute phases. The purpose of the present study is to determine the long-term effects of pre-treatment with APC following SCI in rats. METHODS: The motor function of rats was assessed using the inclined-plane test during 8 weeks after SCI, and the grid runway test 7 weeks after the trauma. Somatosensory evoked potentials (SEPs), brainstem-derived motor evoked potentials (B-MEPs) and corticomotor evoked potentials (CMEPs) were used to quantify axonal function 8 weeks after SCI. Morphometric analysis of the spinal cord lesion was carried out to determine lesion size. Twelve male Sprague-Dawley rats were randomly allocated to either APC (25 IU/kg) or saline group and then subjected to 20 g compression injury of the spinal cord for 20 min at T12. The sham group (n=6) received laminectomy alone. RESULTS: APC significantly reduced the motor disturbances and electrophysiological impairments induced by SCI. APC-treated animals also showed a trend towards a reduction in lesion size. However, this change, was not significant. CONCLUSION: Pre-treatment with APC attenuates the harmful effects of SCI not only during the acute and subacute phases but also in the chronic stage.     

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)     

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.     

大鼠脊髓腹侧左迫损伤后神经营养素及受体表达的变化规律

目的：探讨脊髓损伤后脊髓功能恢复的分子生物学基础。方法：在制作脊髓腹侧压迫损伤的基础上,应用免疫组织化学的方法观察几种神经营养素及其受体表达的变化规律。结果：脊髓腹侧压迫损伤后BDNF,GNDF,NT3,NGF以及TrkA,TrkB,TrkC在伤后3h表达开始增加,伤后72h达到高峰,在伤后2周内其表达维持在相对较高的水平,且以BDNF及TrkB表达最明显。结论：脊髓损伤后这些内源性神经营养素及其受体的大量表达对受损伤脊髓的功能恢复起重要作用。同时也反映了受试动物的脊髓功能受损较重的特点。