Ischemic injury of the spinal cord is rare complication of infrarenal aortic pathology or procedure. So many vascular surgeons are unfamiliar to this complication. But once developed, the impact of this complication is unendurable not only to the patient and his or her family but also to the surgeon. The importance of great anterior medullary artery was well known. Recently, the role of pelvic collateral circulation has been emerged and stressed. In Korea, spinal cord ischemia related to infrarenal aortic pathology or surgical procedure was not reported until recently. Authors had experienced two paraplegic patients, one after elective aortobifemoral bypass due to aortoiliac occlusive lesion in 49 years old male and the other due to acute thrombotic occlusion of infrarenal aorta in 40 years old male. To inform the possibility of ischemic cord injury in infrarenal aortic procedure and pathology, we report our experiences with review of literatures.
Adult ; Aorta ; Aorta, Abdominal ; Arteries ; Collateral Circulation ; Humans ; Korea ; Male ; Methods* ; Middle Aged ; Paraplegia ; Pathology* ; Spinal Cord Ischemia* ; Spinal Cord*

OBJECTIVE: The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. METHODS: Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. RESULTS: The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1alpha and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). CONCLUSION: Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.
Animals ; Aorta ; Caspase 3 ; Catalase ; Cultured Milk Products* ; Diet ; Humans ; Ischemia ; Malondialdehyde ; Neurons ; Neuroprotective Agents* ; Oxidative Stress ; Pathology ; Rats* ; Reperfusion Injury ; Spinal Cord Ischemia ; Spinal Cord* ; Superoxide Dismutase

OBJECTIVETo investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits.

METHODSThirty male New Zealand white rabbits were randomly divided into three groups as follows: puerarin group (n=10) receiving intravenous infusion of 30 mg/kg puerarin for 10 minutes, control group (n=10) receiving intravenous infusion of the same volume of normal saline as puerarin for 10 minutes, and sham operation group (n=10) undergoing only the surgical exposure of the abdominal aorta. Temporary spinal cord ischemia was induced by infrarenal aortic occlusion for 20 minutes and followed by reperfusion. The neural status was scored with the Tarlov criteria at 8, 12, 24 and 48 hours after reperfusion. All the animals were killed at 48 hours after reperfusion and the spinal cords (L5) were removed immediately for histopathological study.

RESULTSThe neural function scores at 8, 12, 24 and 48 hours after reperfusion were higher in the puerarin group and sham operation group than those in the control group (P<0.05). More normal motor neurons in the anterior horn of spinal cord were present in the puerarin group and sham operation group than those in the control group (P<0.01). There was a strong correlation between the final neural function scores and the number of normal motor neurons in the anterior horn of spinal cord (r=0.839, P<0.01).

CONCLUSIONSPuerarin can significantly ameliorate the neural function and the histopathological damages after transient spinal cord ischemia in rabbits.

Animals ; Isoflavones ; pharmacology ; Male ; Motor Neurons ; pathology ; Rabbits ; Spinal Cord Ischemia ; drug therapy ; pathology ; physiopathology ; Vasodilator Agents ; pharmacology

OBJECTIVETo study the effects of Ginkgo biloba extract (GBE) on lipid peroxidation and apoptosis after spinal cord ischemia/reperfusion (I/R) in rabbits.

METHODSSpinal cord I/R injury model was established according to the description of Erten et al. A total of 27 New Zealand white rabbits were divided into three groups randomly: a sham group (9 rabbits treated with sham operation but without aortic occlusion), a model group (9 rabbits treated with aortic occlusion and volume-matched saline), and a GBE group (9 rabbits treated with aortic occlusion and Ginaton (100 mg/kg) injected 30 minutes before aortic clamping and at the onset of reperfusion). The neurological outcomes were evaluated at 24 and 48 hours after reperfusion, respectively. The spinal cord malondialdehyde (MDA) level, superoxide dismutase (SOD) were then detected. Neural cell apoptosis was determined by terminal deoxynucleotidyl t-ransferase (TdT)-mediated dUTP-fluorescence nick end labeling (TUNEL) method and the expression of bcl-2 and bax were examined histologically in the spinal cord with immunohistochemistry.

RESULTSI/R produced a significant decrease in neurological scoring. The motor scores of the GBE group were significantly higher than those of the model group at 24 and 48 hours after reperfusion (P<0.05). Compared with the model group, GBE ameliorated the down-regulation of SOD and produced a significant reduction of the MDA level (P<0.01). The positive cells for TUNEL in the model group were much more than those of the GBE group (P<0.01). The bcl-2 was up-regulated after I/R, especially in the GBE group (P<0.01). The up-regulation of bax was greatly diminished by GBE (P<0.01).

CONCLUSIONSGBE has protective effects against spinal cord I/R injury, and the mechanism may be that it can scavenge oxygen free radicals and inhibit the apoptosis of neural cells.

Animals ; Apoptosis ; drug effects ; Ginkgo biloba ; Lipid Peroxidation ; drug effects ; Malondialdehyde ; analysis ; Neuroprotective Agents ; therapeutic use ; Phytotherapy ; Plant Extracts ; therapeutic use ; Rabbits ; Reperfusion ; Spinal Cord ; drug effects ; pathology ; Spinal Cord Ischemia ; metabolism ; pathology ; Superoxide Dismutase ; analysis

BACKGROUNDLittle is known about neuronal death mechanisms following spinal cord ischemia. The present study aimed to investigate the protective effect of pentoxifylline (PTX) against spinal cord ischemia/reperfusion (I/R) injury.

METHODSRabbits sustained spinal cord ischemia following 45 minutes cross-clamping of the infrarenal aorta. Experimental groups were as follows: the first group of animals (sham, n = 8) underwent laparotomy alone and served as the sham group; the second group (I/R, n = 20) received carrier (3 ml saline solution) and served as the control group; the third group (PTX-A, n = 20) received PTX intravenously 10 minutes prior to ischemia; and the fourth group (PTX-B, n = 20) received PTX intravenously at the onset of reperfusion. Rabbits were evaluated for hind-limb motor function with the Tarlov scoring system at 48 hours. Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosis factor alpha (TNF-alpha) and spinal cords were harvested for myeloperoxidase (MPO) activity, histopathological analysis, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling staining, platelet/endothelial cell adhesion molecule-1 (PECAM-1) and caspase-3 immunohistochemistry, and the number of necrotic and apoptotic neuron were counted and data analyzed at 12, 24, 48 and 72 hours of reperfusion. Spinal cords were studied by electron microscopy.

RESULTSImproved Tarlov scores were seen in PTX-treated rabbits as compared with ischemic control rabbits at 48 hours. A significant reduction was found in TNF-alpha in serum, activity of MPO and immunoreactivity of the PECAM-1 and caspase-3 in PTX-treated rabbits. There were fewer apoptotic neurons than necrotic neurons (P < 0.05). A significant decrease in both necrotic and apoptotic neurons was observed in the PTX-treated groups (PTX-A and PTX-B) compared with the I/R group (P < 0.05). Both necrotic and apoptotic neurons were found with the electron microscope.

CONCLUSIONSPTX may induce protection against ischemia injury in the spinal cord, thereby preventing both necrosis and apoptosis. A major mode of cell death in spinal cord ischemia/reperfusion injury is necrosis while apoptosis is not dominant.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Immunohistochemistry ; In Situ Nick-End Labeling ; Microscopy, Electron, Transmission ; Necrosis ; Pentoxifylline ; pharmacology ; therapeutic use ; Rabbits ; Reperfusion Injury ; prevention & control ; Spinal Cord ; blood supply ; pathology ; ultrastructure ; Spinal Cord Ischemia ; prevention & control ; Vasodilator Agents ; pharmacology ; therapeutic use

The effects of tacrolimus postconditioning on protein-serine-threonine kinases (Akt) phosphorylation and apoptotic cell death in rats after spinal cord ischemia-reperfusion injury were investigated. Ninety male SD rats were randomly divided into sham operation group, ischemia-reperfusion group and tacrolimus postconditioning group. The model of spinal cord ischemia was established by means of catheterization through femoral artery and balloon dilatation. The spinal cord was reperfused 20 min after ischemia via removing saline out of balloon. The corresponding spinal cord segments were excised and determined for Akt activity in spinal cord tissue by using Western blotting at 5, 15, and 60 min after reperfusion respectively. Spinal cord tissue sections were stained immunohistochemically for detection of the phosphorylated Akt expression at 15 min after reperfusion. Flow cytometry was applied to assess apoptosis of neural cells, and dry-wet weights method was employed to measure water content in spinal cord tissue at 24 h after reperfusion. The results showed that the activities of Akt in tarcolimus postconditioning group were significantly higher than those in ischemia-reperfusion group at 5, 15, and 60 min after reperfusion (P<0.05, P<0.01). The Akt activities reached the peak at 15 min after reperfusion in ischemia-reperfusion group and tacrolimus postconditioning group. The percentage of apoptotic cells and water content in spinal cord tissue were significantly reduced (P<0.01) in tacrolimus postconditioning group as compared with those in ischemia-reperfusion group at 24 h after reperfusion. It is concluded that tacrolimus post-conditioning can increase Akt activity in spinal cord tissue of rats, inhibit apoptosis of neural cells as well as tissue edema, and thereby alleviate spinal cord ischemia-reperfusion injury.
Animals ; Apoptosis ; drug effects ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Phosphorylation ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism ; Spinal Cord ; drug effects ; metabolism ; pathology ; Spinal Cord Ischemia ; drug therapy ; metabolism ; Tacrolimus ; pharmacology ; therapeutic use ; Up-Regulation

OBJECTIVETo study the sequential changes of HIF-1alpha (hypoxia-inducible factor 1 alpha) in experimental spinal cord injury in rats and to analyze its potential effects in SCI.

METHODSA static compression model of SCI was employed in this study. Expressions of HIF-1alpha were measured with immunohistochemical staining, while flow cytometry was used to determine the apoptotic ratio and bcl-2 expressions.

RESULTSHIF-1alpha began to increase 1 day after injury, and reached the peak at 3-7 days. Two weeks later, it declined significantly. The sequential changes of HIF-1alpha coincided well with the alterations of apoptotic ratio and contents of bcl-2.

CONCLUSIONSHIF-1alpha possibly participates in the secondary ischemic and hypoxic procedures after spinal cord injury, and may mediate the traumatic apoptosis. Further understanding of HIF-1alpha may provide new therapeutic regimens for SCI.

Animals ; Apoptosis ; Biomarkers ; analysis ; DNA-Binding Proteins ; analysis ; metabolism ; Disease Models, Animal ; Female ; Flow Cytometry ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Injury Severity Score ; Ischemia ; pathology ; Nuclear Proteins ; analysis ; metabolism ; Probability ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism ; pathology ; Transcription Factors

OBJECTIVE: The purpose of this study was to determine whether xenon post-conditioning affects mTOR signaling as well as endoplasmic reticulum stress (ERS)-apoptosis pathway in rats with spinal cord ischemia/reperfusion injury. METHODS: Fifty male rats were randomized equally into sham-operated group (Sham group), I/R model group (I/R group), I/R model+ xenon post-conditioning group (Xe group), I/R model+rapamycin (a mTOR signaling pathway inhibitor) treatment group (I/R+ Rapa group), and I/R model + xenon post- conditioning with rapamycin treatment group (Xe + Rapa group).. In the latter 4 groups, SCIRI was induced by clamping the abdominal aorta for 85 min followed by reperfusion for 4 h. Rapamycin (or vehicle) was administered by daily intraperitoneal injection (4 mg/kg) for 3 days before SCIRI, and xenon post-conditioning by inhalation of 1∶1 mixture of xenon and oxygen for 1 h at 1 h after initiation of reperfusion; the rats without xenon post-conditioning were given inhalation of nitrogen and oxygen (1∶ 1). After the reperfusion, motor function and histopathologic changes in the rats were examined. Western blotting and real-time PCR were used to detect the protein and mRNA expressions of GRP78, ATF6, IRE1α, PERK, mTOR, p-mTOR, Bax, Bcl-2 and caspase-3 in the spinal cord. RESULTS: The rats showed significantly lowered hind limb motor function following SCIRI (P < 0.01) with a decreased count of normal neurons, increased mRNA and protein expressions of GRP78, ATF6, IRE1α, PERK, and caspase-3, and elevated p-mTOR/mTOR ratio and Bax/Bcl-2 ratio (P < 0.01). Xenon post-conditioning significantly decreased the mRNA and protein levels of GRP78, ATF6, IRE1α, PERK and caspase-3 (P < 0.05 or 0.01) and reduced p-mTOR/mTOR and Bax/Bcl-2 ratios (P < 0.01) in rats with SCIRI; the mRNA contents and protein levels of GRP78 and ATF6 were significantly decreased in I/R+Rapa group (P < 0.01). Compared with those in Xe group, the rats in I/R+Rapa group and Xe+Rapa had significantly lowered BBB and Tarlov scores of the hind legs (P < 0.01), and caspase-3 protein level and Bax/Bcl-2 ratio were significantly lowered in Xe+Rapa group (P < 0.05 or 0.01). CONCLUSION By inhibiting ERS and neuronal apoptosis, xenon post- conditioning may have protective effects against SCIRI in rats. The mTOR signaling pathway is partially involved in this process.
Animals ; Apoptosis ; Caspase 3/metabolism* ; Endoplasmic Reticulum Stress ; Endoribonucleases/pharmacology* ; Injections, Intraperitoneal ; Male ; Neurons/pathology* ; Nitrogen/metabolism* ; Oxygen/metabolism* ; Protein Serine-Threonine Kinases ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; RNA, Messenger/metabolism* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Sirolimus/pharmacology* ; Spinal Cord Ischemia/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Xenon/therapeutic use* ; bcl-2-Associated X Protein/metabolism*