Spinal Cord Reperfusion Injury Research Articles

Tanshinone Protects against Spinal Cord Ischemia-Reperfusion Injury by Inhibiting JNK Activity.

Spinal cord reperfusion injury as a secondary damage after primary spinal cord injury is an important factor causing nerve cell damage. In this study, we aim to investigate the effects and mechanisms of tanshinone (TAE) in the rabbit spinal cord during ischemia-reperfusion. New Zealand white rabbits were randomly divided into 3 groups: sham-operated group (5 rabbits), ischemia-reperfusion group (0.9% TAE was administered intraperitoneally 30 min before ischemia, and 4 groups of 5 rabbits each according to different time periods of reperfusion: group A reperfused for 0.5 h, group B reperfused for 2 h, group C reperfused for 8 h, and group D reperfused for 24 h), and TAE group (an ischemia-reperfused for 24 h). Group A was reperfused for 0.5 h, group B for 2 h, group C for 8 h, group D for 24 h, and group TAE (TAE was applied 30 min before ischemia reperfusion, grouped as ischemia-reperfusion group). The expression of JNK (c-Jun NH2-terminal Kinase) and phosphorylation-JNK (p-JNK) in spinal cord tissues of each group were detected by Western blot. Light and electron microscopy showed that early apoptosis started in group B in the ischemia-reperfusion group, while early apoptosis appeared only in group D in the tanshinone intervention group. Western blot showed that p-JNK expression started in group B in the ischemia-reperfusion group and gradually increased with the prolongation of ischemia time, while p-JNK expression only increased in group D in the tanshinone intervention group. In the tanshinone intervention group, p-JNK was activated only in group D and its activity was less than that in the ischemia-reperfusion group; the protein expression of JNK did not change significantly in both groups. Spinal cord ischemia-reperfusion can cause spinal cord injury by activating the signaling molecule JNK (MRPKs family), and early tanshinone intervention can partially inhibit this injury. Our finding provides a new idea and theoretical basis for clinical treatment of spinal cord ischemia-reperfusion injury.

Spinal Cord Reperfusion Injury after Decompression of Severe Cord Compression: Critical Care Management

Spinal Cord Reperfusion Injury after Decompression of Severe Cord Compression: Critical Care Management

경추증성 척수증에 대한 수술에서 재관류손상의 수술중신경계감시

Neurologic deficit after cervical decompressive surgery for cervical spondylotic myelopathy is a rare but critical complication. Spinal cord reperfusion injury is one of the major causes of sudden neurologic deterioration associated with the surgery. If reperfusion injury occurs during the surgery, intraoperative neurophysiologic monitoring is essential for early diagnosis and intervention including surgical modification and maintaining proper mean blood pressure to reverse the neurologic damage. We review reperfusion injury in surgery for cervical spondylotic myelopathy.

The Efficacy of Combined Medication With Methylprednisolone and Erythropoietin in the Treatment of Ischemia-Reperfusion Injury to the Spinal Cord in Patients With Cervical Spondylotic Myelopathy.

IntroductionCervical myelopathy (CM) is caused by degenerative or congenital changes in the discs and soft tissues of the cervical spine, leading to chronic compression of the spinal cord. The current treatment for moderate-to-severe CM is surgical decompression, which is effective in most cases; however, it can cause inflammation of the nervous system and spinal cord reperfusion injury, resulting in perioperative neurological complications and suboptimal neurological recovery. The aim of this study was to investigate the therapeutic effects of the combination of erythropoietin and methylprednisolone in the treatment of ischemia-reperfusion injury to the spinal cord and to analyze its effects on the levels of interleukin-1 beta (IL-1β), interleukin-1 receptor antagonist (IL-1RA), and interleukin-8 (IL-8).Materials and methodsThis study included 110 patients admitted to the hospital due to cervical spondylotic myelopathy. They were randomized into two groups of 55 patients each: a control and an observation group. In both groups of patients, fusion internal fixation and anterior cervical discectomy were performed. The difference, however, was that the control group received a rapid intravenous injection of 30 mg/kg methylprednisolone 30 minutes prior to spinal cord decompression, while the observation group received an intravenous injection of 30 mg/kg methylprednisolone and 3,000 U/kg erythropoietin 30 minutes before spinal cord decompression. The study was approved by the Hospital Ethical Committee of the Dow University of Health Sciences, Karachi. The neurological function of both groups of patients was assessed before the procedure and three months after the treatment using the Japanese Orthopedic Association (JOA) method of assessing spinal cord function (40-point rating method). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of neuron-specific enolase (NSE), S-100β, IL-1RA, IL-1β, and IL-8 in both groups. The quality of life of patients in both groups was assessed three months after the treatment with the World Health Organization Quality of Life assessment instrument (WHOQOL-100).ResultsBefore the treatment, there was no significant variance between the two groups in the JOA score and the 40-point rating method. Similarly, there was no significant difference in the levels of IL-1β, IL-1RA, and IL-8 between the two groups (p-value = 0.262, 0.387, and 0.154 respectively) prior to the treatment. Three months after the treatment, the levels of IL-1β and IL-8 in the observation group were 21.83 ±3.65 ng/l and 357.07 ±32.36 ng/l respectively, both lower than the control group value (p-value = 0.026, 0.028 respectively). The level of IL-1RA in follow-up was 21.59 ±1.15 ng/l, which was higher than that in the control group. Three months after the treatment, all the WHOQOL-100 parameters of the observation group for psychology, physiology, social relations, independence, spirituality, environment, and general quality of life were higher than those of the control group; the variance among the groups was statistically significant (p-value: <0.001).ConclusionsThe combination therapy with erythropoietin and methylprednisolone is effective for ischemia-reperfusion injuries of the spinal cord. It also reduces S-100β and NSE, inhibits IL-1β, and increases IL-8 and IL-1RA. Therefore, it preserves and improves spinal nerve function and the quality of life of patients.

Spinal Cord Reperfusion Injury Following a Cervical Laminectomy

Spinal Cord Reperfusion Injury Following a Cervical Laminectomy

White Cord Syndrome: The Terrible Nightmare

Introduction: Reperfusion injury of spinal cord “white cord syndrome” refers to acute neurological deterioration after decompressive spinal surgery without any reported intraoperative events. The postoperative appearance of diffuse hyperintense intramedullary areas in T2-weighted MRI is characteristic without any other pathological or compressive signs. The etiology may be due to sudden expansion of the cord after reperfusion of chronically ischemic areas leading to disruption of blood-spinal cord barrier. The incidence and risk factors of the syndrome are not well documented in the literature. Methods: This is a retrospective case series that included 150 patients with cervical spondylotic myelopathy who had undergone decompression surgery in our institution from 2017 to 2019. Patients’ demographics, clinical, imaging characteristics, intraoperative and postoperative data were collected and analysed. Results: In this study, we documented 7 cases of this syndrome. We found that advanced age, chronic hypertension, pre-existing cord signal in MRI and long history of symptoms may be risk factors for this syndrome. Conclusion: Early diagnosis and prompt treatment of this syndrome with steroids and physical therapy may lead to initial improvement. Awareness of the surgeons about this syndrome should be increased and identifying its risk factors is very important for patients counseling.

Spinal Cord Reperfusion Injury: Case Report, Review of the Literature, and Future Treatment Strategies

A rare complication of cervical spine decompression is acute paralysis following the procedure. This neurologic deficit is thought to be due to reperfusion injury of a chronically ischemic spinal cord and is referred to as "white cord syndrome" given the pathognomonic finding of hyperintensity on T2-weighted MRI. Three prior cases have been reported. We present a case of transient quadriplegia following posterior cervical decompression.A 41-year-old male with cervical spondylotic myelopathy presented with bilateral progressive upper extremity weakness, hyperreflexia, and cervical spine MRI showing severe cord compression at C1 and partial hyperintense signal. Intraoperatively, after C1 bony decompression and without perceptible technical cause, the patient experienced a complete loss of both somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) with an eventual return to baseline prior to completing the operation.The patient awoke from surgery with acute quadriplegia without perceptible technical cause (intraoperative compression or evident anatomic compromise). An immediate postoperative MRI revealed a more pronounced hyperintensity in the central cervical cord on T2-weighted sequences. Treatment with increased mean arterial pressure (MAP) therapy and dexamethasone resulted in the patient regaining some movement over a period of hours and full strength over a period of months.The mechanism of acute weakness following cervical spine decompression in the absence of perceptible technical cause is not fully understood, but current theory suggests that a reperfusion injury is most likely the cause. It remains a diagnosis of exclusion. Familiarity with this potential postoperative complication can aid in appropriate postoperative therapy with early diagnosis and intervention leading to restored spinal cord function and excellent prognosis.

Methylprednisolone treatment enhances early recovery following surgical decompression for degenerative cervical myelopathy without compromise to the systemic immune system

BackgroundDegenerative cervical myelopathy (DCM) is caused by degenerative or congenital changes to the discs and soft tissues of the cervical spine, which leads to chronic compression of the spinal cord. The current treatment for moderate to severe DCM consists of surgical decompression, which, while effective in most cases, can result in neuroinflammation and spinal cord reperfusion injury, leading to perioperative neurological complications and suboptimal neurological recovery. The primary objective of this study was to assess, in a translationally relevant animal model of DCM, the efficacy of perioperative methylprednisolone (MP) in enhancing neurological recovery and to evaluate its effect on the inflammatory response following decompression.MethodsDCM was induced in C57BL/6 mice. Briefly, an aromatic polyether material was implanted underneath the C5-C6 laminae to cause progressive compression of the cervical spinal cord due to focal ossification. Decompressive surgery was undertaken at 12 weeks post initial biomaterial implantation. Animals received one dose of MP (30 mg/kg) or vehicle 30 min before decompression and at 2 weeks after decompression. Acute analysis of secreted cytokines and spinal cord microvasculature was complemented with immunohistochemistry for glial and neuronal cell markers. Locomotor outcomes were measured using the CatWalk system. The composition of circulating white blood cells was analyzed by flow cytometry.ResultsA single dose of MP before decompression significantly sped locomotor recovery (*p < 0.05) and reduced the incidence of perioperative motor complications, without affecting the composition of circulating white blood cells. Histological assessment of the spinal cord showed significant neuronal preservation and a modest reduction in parenchymal inflammation.ConclusionsOur data suggest that MP reduces perioperative neurological complications following decompressive surgery for DCM by protecting neurons from inflammation, without compromising the composition of circulating immune cells. We propose that MP, which is commonly used for neurological disorders including spinal cord injury, be considered as a perioperative adjunct to decompressive surgery to attenuate neurological complications.

Morphologic analysis of spinal cord ischemia ‐ reperfusion injury caused by aortic cross clamping in a rat model

BackgroundSpinal cord ischemia and paralysis of lower extremities are devastating postoperative complications that accompany surgery of aortic aneurysm. Spinal cord ischemia ‐ reperfusion injury (I/R) results in overproduction of reactive species leading to tissue oxidative stress, which impact the neuronal network in spinal cord as well as supporting white matter cells. Here, we report the longitudinal analysis of activity and number of neurologic cells in the area of aortic clamping.MethodsTransient aortic occlusion was produced in rats by cross – clamping of the abdominal aorta for 45 minutes. Animals were sacrificed at several time points after reperfusion; 1, 6 and 48h; to determine time correlated changes in activity and number of neurologic cells in spinal cord. Spinal cord tissue was analyzed by immunofluorescence using specific primary antibodies, glial fibrillary acid protein (GFAP) and NeuN. Also, we wondered whether survival of neurons was related to their expression of nuclear factor erythroid 2‐related factor 2 (Nrf2), an oxidative stress protective protein.ResultsIn the present study, ischemia – reperfusion injury of spinal cord was manifested by moderate loss of neurons in dorsal horn after 6h of reperfusion, and significant loss of neurons in dorsal horn after 48h of reperfusion compared to sham animals. Neurons located ventrally and laterally indicated no change in number. Surviving neuron cells, howerver, showed expression of Nrf2 with its nuclear translocation escpecially pronounced in neurons located in ventral horn. Longitudinal analysis of neuronal number showed that loss of neurons in dorsal horn was limited to lumbar part of spinal cord. Analysis of GFAP positive cells revealed moderate increase in number 6h post reperfusion in lateral part of spinal cord, while 48h post reperfusion this increase was even more pronounced compared to sham animals. Increase of number of GFAP positive cells was followed with astrocyte activation in lateral part of spinal cord presented as increased GFAP positive area in the same part of spinal cord. Longitudinal analysis of spinal cord revealed that astrocyte activation is present even in thoracic parts of spinal cord, higher than segments which were targeted by aortal clamping.ConclusionOur data indicate that I/R spinal cord injury induces changes in number of GFAP and NeuN positive cells and these changes correlate to duration of reperfusion time. The surviving neurons express Nrf2 in their nucleus, which shows the involvement of Nrf2 pathway in neuron survival.Support or Funding InformationGrant approved and financed by Faculty of Medicine University of Rijeka

CaSR and calpain contribute to the ischemia reperfusion injury of spinal cord

Spinal cord ischemia reperfusion injury (SCIRI) can cause spinal cord dysfunction and even devastating paraplegia. Calcium-sensing receptor (CaSR) and calpain are two calcium related molecules which have been reported to be involved in the ischemia reperfusion injury of cardiomyocytes and the subsequent apoptosis. Here, we studied the expression of CaSR and calpain in spinal cord neurons and tissues, followed by the further investigation of the role of CaSR/calpain axis in the cellular apoptosis process during SCIRI. The results of in vitro and in vivo studies showed that the expression of CaSR and calpain in spinal cord neurons increased during SCIRI. Moreover, the CaSR agonist GdCl3 and antagonist NPS-2390 enhanced or decreased the expression of CaSR and calpain respectively. The expressions of CaSR and calpain were also consistent with the cellular apoptosis in spinal cord. Taken together, CaSR-calpain contributes to the SCIRI apoptosis, and CaSR antagonist might be a helpful drug for alleviating SCIRI.

Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway

Resveratrol, a polyphenol found in various plants, including grapes, plums and peanuts has shown various medIRInal properties, including antioxidant, protection of cardiovascular disease and cancer risk. However, the effects of resveratrol on spinal cord reperfusion injury have not been investigated. Hence, the present study was designed to evaluate the effect of resveratrol on nitric oxide synthase (iNOS)/p38MAPK signaling pathway and to elucidate its regulating effect on the protection of spinal cord injury. Spinal cord ischemia–reperfusion injury (IRI) was performed by the infrarenal abdominal aorta with mini aneurysm clip model. The expressions of iNOS and p38MAPK and the levels of biochemical parameters, including nitrite/nitrate, malondialdehyde (MDA), advanced oxidation products (AOPP), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in control and experimental groups. IRI-induced rats treated with 10 mg/kg resveratrol protected spinal cord from ischemia injury as supported by improved biological parameters measured in spinal cord tissue homogenates. The resveratrol treatment significantly decreased the levels of plasma nitrite/nitrate, iNOS mRNA and protein expressions and phosphorylation of p38MAPK in IRI-induced rats. Further, IRI-produced free radicals were reduced by resveratrol treatment by increasing enzymatic and non-enzymatic antioxidant levels such as GSH, SOD and CAT. Taken together, administration of resveratrol protects the damage caused by spinal cord ischemia with potential mechanism of suppressing the activation of iNOS/p38MAPK pathway and subsequent reduction of oxidative stress due to IRI.

Suspicious Reperfusion Injury of Spinal Cord After Multilevel Cervical Posterior Decompression without Remarkable Surgical Insult: Two Case Reports

Suspicious Reperfusion Injury of Spinal Cord After Multilevel Cervical Posterior Decompression without Remarkable Surgical Insult: Two Case Reports

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury.

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30–180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in-creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potential latency can reflect the degree of spinal cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury.

The protective effect of low-dose methotrexate on ischemia–reperfusion injury of the rabbit spinal cord

Methotrexate was developed as a cytostatic agent, but at low doses, it has shown potent anti-inflammatory activity. Previous studies have demonstrated that the anti-inflammatory effects of methotrexate are primarily mediated by the release of adenosine. In this study, we hypothesized that low-dose methotrexate has protective effects in spinal cord ischemia–reperfusion injury. Rabbits were randomized into the following four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (methotrexate). In the control group only a laparotomy was performed. In all the other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery. Neurological evaluation was performed with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, as were the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural evaluations were also performed. After ischemia–reperfusion injury, increases were found in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both serum and tissue catalase levels were decreased. After the administration of a low-dose of methotrexate, decreases were observed in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both the serum and tissue catalase levels were increased. Furthermore, low-dose methotrexate treatment showed improved results concerning the histopathological scores, the ultrastructural score and the Tarlov scores. Our results revealed that low-dose methotrexate exhibits meaningful neuroprotective activity following ischemia–reperfusion injury of the spinal cord.

Alpha-tocopherol ameliorates oxidative renal insult associated with spinal cord reperfusion injury

Ischemic-reperfusion procedures targeting a specific organ often results in remote multiple organ injuries mediated possibly by heightened oxidative stress levels. As the kidney is one of the most vulnerable organs for ischemic oxidative stress, the aim of the present study was to confirm the occurrence of renal complication secondary to spinal cord ischemic-reperfusion injury (SC-IRI) induced by aortic clamping. The study also investigated the possible prophylactic effect of long-term administration of α-tocopherol (α-TOL) against high level of renal oxidative stress and inflammatory processes induced by SC-IRI. In this study, a total of 60 male Sprague-Dawley rats were randomly divided into five equal groups: C group underwent no surgery; CE group received α-TOL 600 mg/kg intramuscular twice weekly for 6 weeks; S group were subjected to laparotomy without clamping of the aorta; SE group were handled as S group and treated with α-TOL as group CE; SC-IRI group were subjected to laparotomy with clamping of the aorta just above the bifurcation of the aorta for 45 min, then the clamp was released for 48 h for reperfusion. SC-IRIE group was subjected to IRI as in group SC-IRI and was injected with α-TOL in the same dose and route as α-TOL-treated control group. SC-IRI resulted in increases in serum creatinine, blood urea nitrogen, plasma nitrite/nitrate level, serum tumor necrosis factor alpha, renal tissue homogenate level for malondialdehyde, superoxide dismutase and prostaglandin E2. Long-term prophylactic treatment with α-TOL resulted in amelioration of the renal functional disturbances and all measured parameters of oxidative stress and inflammation. Ischemic reperfusion injury of the spinal cord induced some remote renal functional disturbances although some of the observed changes may have resulted from decreased renal blood flow due to the hypotension induced during the procedure. Prophylactic long-term α-TOL administration guards against the renal function disturbances an effect that can be attributed, at least partially, to improvement of the renal pro-oxidant/antioxidant balance and inhibition of the inflammatory processes.

Ischemic postconditioning protects the spinal cord from ischemia–reperfusion injury via modulation of redox signaling

It is well known that ischemic postconditioning reduces ischemic-reperfusion injury, but the underlying mechanism is not fully understood. The current study investigated the role of reactive oxygen species-mediated upregulation of endogenous antioxidant enzymes in the generation of a protective effect induced by ischemic postconditioning against spinal cord reperfusion injury in the rabbit. New Zealand White rabbits were randomly allocated to sham, ischemia-reperfusion, and postconditioning groups (3 cycles of 30 seconds of reperfusion and 30 seconds of occlusion during the onset of reperfusion). Spinal cord ischemia was induced by clamping the infrarenal abdominal aorta for 20 minutes in the ischemia-reperfusion and postconditioning groups. Forty-eight hours after reperfusion, the neurologic status of the lower limbs was assessed. Blood samples were collected for analysis of serum neuron-specific enolase levels, and the lumbar spinal cord segments (L5-7) were harvested for histopathologic and antioxidant enzyme activities and mRNA analysis with or without administration of N-2-mercaptopropionylglycine (an effective oxygen free radical scavenger) given at different reperfusion times. Continuous administration of N-2-mercaptopropionylglycine for 13 minutes, starting at 10 minutes before (but not 10 minutes after) the beginning of reperfusion, attenuated the neuroprotective effect of postconditioning against spinal cord ischemia and reversed the increase in activity of the antioxidant enzymes superoxide dismutase and catalase in spinal cord tissue subjected to ischemic postconditioning. The results indicate that reactive oxygen species-triggered upregulation of endogenous antioxidant enzyme activities may be involved in the mechanism of neuroprotection of ischemic postconditioning.

A potential protective effect of α-tocopherol on vascular complication in spinal cord reperfusion injury in rats

BackgroundParaplegia remains a potential complication of spinal cord ischemic reperfusion injury (IRI) in which oxidative stress induced cyclooxygenase activities may contribute to ischemic neuronal damage. Prolonged administration of vitamin E (α-TOL), as a potent biological antioxidant, may have a protective role in this oxidative inflammatory ischemic cascade to reduce the incidence of paraplegia. The present study was designed to evaluate the preventive value of α-TOL in IRI of spinal cord.MethodsFor this study, 50 male Sprague-Dawley rats were used and divided into five experimental groups (n = 10): Control group (C); α-TOL control group (CE) which received intramuscular (i.m.) α-TOL injections (600 mg/kg); Sham operated group (S), IRI rats were subjected to laparotomy and clamping of the aorta just above the bifurcation for 45 min, then the clamp was released for 48 hrs for reperfusion; and IRIE rats group, received 600 mg/kg of α-TOL i.m. twice weekly for 6 weeks, followed by induction of IRI similar to the IRI group. At the end of the experimental protocol; motor, sensory and placing/stepping reflex evaluation was done. Plasma nitrite/nitrate (NOx) was measured. Then animals' spinal cord lumbar segments were harvested and homogenized for measurement of the levels of prostaglandin E2 (PGE2), malondialdehyde (MDA) and advanced oxidation products (AOPP), while superoxide dismutase (SOD) and catalase (CAT) activity were evaluated.ResultsInduction of IRI in rats resulted in significant increases in plasma levels of nitrite/nitrate (p < 0.001) and spinal cord homogenate levels of PGE2, MDA, advanced oxidation protein products AOPP and SOD with significant reduction (p < 0.001) in CAT homogenate levels. Significant impairment of motor, sensory functions and placing/stepping reflex was observed with IRI induction in the spinal cord (p < 0.001). α-TOL administration in IRIE group significantly improved all the previously measured parameters compared with IRI group.Conclusionsα-TOL administration significantly prevents the damage caused by spinal cord IRI in rats with subsequent recovery of both motor and sensory functions. Alpha-tocopherol improves the oxidative stress level with subsequent reduction of the incidence of neurological deficits due to spinal cord IRI conditions.

Sevoflurane Postconditioning Attenuates Spinal Cord Reperfusion Injury Through Free Radicals-Mediated Up-Regulation of Antioxidant Enzymes in Rabbits

Paraplegia is one of the most common complications following aortic aneurismal surgery. The present study examined the hypothesis that neuroprotection of sevoflurane postconditioning (PostC) against spinal cord reperfusion injury is associated with free radicals-mediated up-regulation of antioxidant enzymes in rabbits. New Zealand White rabbits were subjected to sevoflurane PostC, oxygen (O(2)), or sham treatment at the onset of spinal cord reperfusion for 10 min. Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. Forty-eight hours after reperfusion, the motor function of the lower limbs was evaluated and the lumbar spinal cord segment (L5-7) was harvested for histopathologic and biochemical analyses in the presence or absence of N-2-mercaptopropionylglycine, a potent oxygen free radical scavenger. Activities of superoxide dismutase and catalase in spinal cord tissue were increased in the sevoflurane PostC group 1 h after reperfusion and retained a higher level 6 or 24 h after reperfusion. Sevoflurane PostC produced a significant reduction of the malondialdehyde content at 6, 24, and 48 h after reperfusion. A 20 min continuous administration of N-2-mercaptopropionylglycine starting 10 min before the beginning of PostC attenuated the neuroprotective effect against spinal cord ischemia, and reversed the increase of the two enzyme activities in spinal cord tissue induced by sevoflurane PostC. An initial oxidative stress, as a trigger to up-regulate the antioxidant enzyme activities, plays an important role in the protection of sevoflurane PostC against spinal cord reperfusion injury.

Early adenosine receptor activation ameliorates spinal cord reperfusion injury

Adenosine receptor activation at reperfusion has been shown to ameliorate ischemia-reperfusion injury of the spinal cord, but the effects of therapy given in response to ischemic injury are unknown. We hypothesized that adenosine receptor activation with ATL-146e would produce similar protection from ischemic spinal cord injury, whether given at reperfusion or in a delayed fashion. Twenty-two New Zealand white rabbits were divided into three groups. All three groups, including the ischemia-reperfusion group (IR, n = 8), underwent 45 min of infrarenal aortic occlusion. The early treatment group (early, n = 8) received 0.06 mug/kg/min of ATL-146e for 3 h beginning 10 min prior to reperfusion. The delayed treatment group (delayed, n = 6) received ATL-146e starting 1 h after reperfusion. After 48 h, hind limb function was graded using the Tarlov score. Finally, lumbar spinal cord neuronal cytoarchitecture was evaluated. Hemodynamic parameters were similar among the groups. Hind limb function at 48 h was significantly better in the early group (3.5 +/- 1.0) compared to the IR group (0.625 +/- 0.5, P < or = 0.01). There was a trend towards better hind limb function in the early group compared to the delayed group (2.4 +/- 1.1, P = 0.08). Hind limb function was similar between delayed and IR groups. Hematoxylin-eosin spinal cord sections demonstrated preservation of viable motor neurons in the early group compared to the delayed and IR groups. Early therapy with ATL-146e provided better protection in this study; therefore, therapy should not be delayed until there is evidence of ischemic neurological deficit. This study suggests that adenosine receptor activation is most effective as a preventive strategy at reperfusion for optimal protection in spinal cord ischemia-reperfusion injury.

Tissue xanthine oxidase activity and nitric oxide levels after spinal cord ischemia/reperfusion injury in rabbits: comparison of caffeic acid phenethyl ester (CAPE) and methylprednisolone

AbstractCaffeic acid phenethyl ester exhibits antioxidant properties. This experimental study was designed to determine the effect of CAPE on nitric NO level and XO activity after reperfusion injury of spinal cord. New Zealand white rabbits were undergone aortic occlusion. CAPE, methylprednisolone or saline were injected intraperitoneally before surgical intervention. Animals were subjected to 21 min of crossclamp time. At the end of occlusion time, the clamps were removed and restoration of the blood flow was verified visually. Animals in sham group underwent a surgical procedure similar to the other groups but the aorta was not occluded. Spinal cord specimens were obtained to determine the tissue levels of NO and XO activity.Both XO activity and NO level in ischemia group were significantly higher than those of sham group (p = 0.0005 and 0.0003, respectively). MP and CAPE had no effect on XO activity after reperfusion. These two agents decreased NO levels nearly to that of sham group after reperfusion. There were no differences between MP and CAPE on reducing NO level. These results suggest that rabbits with ischemia‐reperfusion injury in spinal cord have increased cord concentrations of nitrite and nitrate that are indicative of endogenous overproduction of NO. CAPE may be regarded as an agent that protects spinal cord from ischemia‐reperfusion injury.