Carbon Dioxide at Anesthetic Levels Protects against Irreversible Damage during Spinal Cord Ischemia

Mild Hypothermia Protects against Irreversible Damage during Prolonged Spinal Cord Ischemia

Vascular Occlusion Produced over 24 Hours Increases Spinal Cord Tolerance to Occlusion

Spinal Cord Protection with a Cerebrospinal Fluid Drain in a Patient Undergoing Thoracic Endovascular Aortic Repair

Paraplegia prevention branches: A new adjunct for preventing or treating spinal cord injury after endovascular repair of thoracoabdominal aneurysms

Objective To investigate the effect of different programs of preconditioning with hyperbaric oxygen (HBO) on spinal cord ischemia-reperfusion injury (I/R) in rabbits. Methods Forty-five New Zealand rabbits aged 4-5 months weighing 2.0-2.5 kg were randomly divided into 5 groups: group S, sham operation ( n = 5);group IR, spinal cord I/R injury (n = 10);group H_(1～3) , the animals were pretreated with 100% O_2 at 2.5 ATA 1 h/d for 5 (group H_1 ), 10 (group H_2 ) , or 20 (group H_3 ) consecutive days respectively 24 h before spinal cord I/R. The animals were anesthetized with iv pentobarbital sodium 30 mg/kg. The artery in the ear and left femoral artery were cannulated for proximal and distal mean blood pressure monitoring. Spinal cord ischemia was produced by cross-clamping of abdominal aorta distal to renal artery for 20 min. Hind-limb motor function was assessed at 48 h after reperfusion according to the modified criteria established by Tarlov (0 = no spontaneous movement, 4= normal motor function) . The animals were then killed and the L_5 segment of the spinal cord was removed for detection of neuronal survival (by HE staining), apoptosis (by TUNEL) and degeneration (by Fluoro-Jade B staining). Results Preconditioning with 5 or 10 d of HBO improved the hind-limb motor function and preserved more normal neurons in the spinal cord after I/R injury. Both apoptotic and degenerative cell death were attenuated in H_1 and H_2 groups. There was no significant difference in hind-limb motor dysfunction and the number of normal neurons in the lumbar spinal cord between H_3 group and I/R group. Conclusion Preconditioning with 5 d or 10 d HBO induces tolerance against spinal cord I/R injury, whereas preconditioning with 20 d of HBO fails to protect the spinal cord from I/R injury. Key words: Hyperbaric oxygenation; Ischemic preconditioning; Reperfusion injury; Spinal cord

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.

PII: S0022-5223(99)70128-5

It has recently been revealed that during the aorta-clamped period, D-Ala2, D-Leu5-Enkephalin (DADLE) infusion can protect the spinal cord against ischemia and reperfusion (I/R) injury. However, the protective effects of DADLE administration prior to ischemia or at the time of early reperfusion have not yet been investigated. Drug pre- or post-conditioning can serve as a more valuable clinical strategy. Therefore, the present study was designed to investigate the neuroprotective effect of DADLE infusion at different time intervals in order to determine the optimum time point for ischemic spinal cord protection. A total of 40 New Zealand white rabbits were randomly divided into 5 groups: Sham-operated (Sham), normal saline pre-conditioning (NS), DADLE per-conditioning (Dper), DADLE pre-conditioning (Dpre) and DADLE post-conditioning (Dpost). All animals were subjected to spinal cord ischemia for 30 min followed by 48 h reperfusion. Hind limb motor functions were assessed according to the Tarlov criterion when the animals regained consciousness, 6, 24 and 48 h after reperfusion. Histological analysis and the number of viable α-motor neurons were also used to assess the extent of spinal cord injury. Compared with the NS group, the Tarlov scores and the number of normal neurons were significantly higher in the Dper group (P<0.05), which were consistent with the results of a previous study. In addition, the paraplegia rate and loss of normal motor neurons were lower in the DADLE per- and post-conditioning groups compared with the DADLE pre-conditioning; however, these were not statistically significant. DADLE 0.05 mg/kg administration at three time points all mitigated normal motor neuron injury in the anterior horn and decreased the paraplegia rates in rabbits. The therapeutic benefits appeared best in the post-conditioning group with DADLE, and worst in the pre-conditioning group.

To investigate whether postconditioning with sevoflurane could alleviate spinal cord ischemia reperfusion injury in rabbits, and whether the beneficial effect is dependent on oxygen free radicals. In Experiment 1, 48 male New Zealand white rabbits were randomly assigned to six groups (n=8 each). Animals in the sham group only underwent sham-operation. Animals in the control group underwent spinal cord ischemia for 20 min without postconditioning. Animals in 02 postconditioning group (Group O2) inhaled 100% O2 from 5 min before reperfusion and lasted 13 min. Animals in sevoflurane postconditioning groups (Group Sevo0.5, Sevo1.0 and Sevo1.5) inhaled 0.5, 1.0, 1.5 minimum alveolar concentration (MAC) sevoflurane in 100% O2 from 5 min before reperfusion and lasted 10 min, then inhaled 100% O2 for 3 min to wash out the remaining sevoflurane. In Experiment 2, 36 male New Zealand White rabbits were randomly assigned to four groups (n=9 each). Animals in O2 and Sevo groups received normal saline (5 ml/kg intravenously) 1 h before postconditioning with 100% O2 and 1.0 MAC sevoflurane, respectively. In the DMTU + Sevo and DMTU + O2 groups, 5 ml/kg of 10% dimethylthiourea (DMTU, a potent oxygen free radical scavenger, dissolved in saline) was administered intravenously at the same time. Spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, hind-limb motor function and histopathology of the spinal cord were examined in a blinded fashion. (1) The neurologic and histopathologic outcomes in the sevoflurane postconditioning groups were better than those in the control group (P < 0.05), the histopathologic outcomes in Sevo1.0 group were better than that in Sevo0.5 and Sevo1.5 groups (P < 0.05). (2) The neurologic and histopathologic outcomes in Sevo, DMTU + Sevo and DMTU + O2 groups were better than those in the O2 group (P < 0.05), the histopathologic outcomes in Sevo group were better than that in the DMTU + Sevo and DMTU + O2 groups (P < 0.05). Our study demonstrates that sevoflurane postconditioning against spinal cord ischemia injury via the release of oxygen free radicals in rabbits.

Objective To provide the theoretical basis for the application of cortical somatosensory evoked potential (CSEP) in monitoring the function of the spinal cord to prevent postoperative neurological dysfunction. Methods Thirty-three New Zealand rabbits were randomly divided into 6 groups: 8 were chosen as control group to eliminate the influence of anesthesia and surgery on the evoked potential; the other 25 were assigned to 5 sub-experimental groups (n=5) according to the artery number being ligatured in the left renal arteries and the spinal arteries. Baseline evoked potential in each group was noted immediately after anesthesia; the CSEP were recorded at different time points (before vascular ligation, 30 min and 2 d after vascular ligation). Motor functions were assessed after narcotic conscious and 2 d after vascular ligation. The specimens were taken for HE staining. Results The latency was not sensitive to spinal cord ischemia and no significant difference of that was found between the experimental groups and the control group (P>0.05); except that, the changes of theamplitudes were very complex and the specificity of motor function was decreased. The amplitude reduced and then gradually restored in the 2, 3 and 4 levels of ligation. The changes of amplitude could indicate the degree of pathological damage in the spinal cord and its motor function. Conclusion Complex amplitude of somatosensory evoked potential can be found in the acute phase of ischemia in the spinal cord. Specificity of motor function is poor resulting from its signal averaging process. Motor evoked potential monitoring in the operation should also be added in the detection of the spinal cord. Key words: Cortical evoked potentials; Motor function; Ischemia in the spinal cord

Protective effect of delta opioid agonist [d-Ala2, d-Leu5] enkephalin on spinal cord ischemia reperfusion injury by regional perfusion into abdominal aorta in rabbits

Objective To investigate the effect of early evaluation of cortical somatosensory evoked potentials(CSEP)and desending neurogenic motor evoked potentials(DNEP)in spinal cord ischemic injury by observing the early change characteristics of CSEP and DNEP of spinal cord ischemia in rabbits. Methods To establish a rabbit model with different degree of permanent spinal cord ischemic injury through the ligation of different levels of lumbar arteries. The rabbits were divided into 5 groups(ligation of the left renal artery and the different levels of lumbar arteries between arterial bifurcations respectively, including 1 to 5-artery group). After modeling, CSEP and DNEP were continuously recorded for 60 min. After 2 days, the samples of ischemic central area were selected for HE staining. The motor function score Tarlov criteria were used to assess the motor function. The relationship between the amplitude variation of CESP and DNEP and the motor function after ligation were analyzed. Results There were statistical significance in the percentages of the CSEP amplitude and preoperative baseline amplitude between the 4- and 5-artery groups compared with before ligation(P 0.05). There were statistical differences in the percentages of the DNEP amplitude and preoperative baseline amplitude among the 3-, 4- and 5 artery groups compared with before ligation(all P 0.05). Compare with before ligation, there were statistical significances in the motor function 2 days after ligation between the 4- and 5-artery group(all P 0.05). The amplitude variation of CSEP and DNEP was positively correlated with the motor function 2 days after ligation of blood vessels(r=0.97, P<0.001; r=0.95, P<0.001). Conclusions Both CSEP and DNEP can predict the motor function after spinal cord injury. DNEP is more sensitive to spinal cord ischemic injury and is more specific to motor function. It can find ischemic injury in the early spinal cord ischemia. Key words: Spinal cord ischemia; Evoked potentials, somatosensory; Evoked potentials, motor; Rabbits

Calcium/calmodulin-dependent protein kinase II inhibition using tatCN19o ameliorates spinal cord ischemia associated with aortic surgery.

Effects of Cyclosporin A on Neurological Outcome and Serum Biomarkers in the Same Setting of Spinal Cord Ischemia Model

In vivo adenovirus-mediated gene transfer and expression in ischemic rabbit spinal cord