Erythropoietin during porcine aortic balloon occlusion-induced ischemia/reperfusion injury

Simon, Florian; Scheuerle, Angelika; Calzia, Enrico; Bassi, Gabriele; Öter, Şükrü; Duy, Cuong Nguyen; Kick, J.; Brückner, U. B.; Radermacher, Peter; Schelzig, Hubert

doi:10.1097/ccm.0b013e31817d7912

Cited by 41 publications

(49 citation statements)

References 51 publications

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“…Anesthesia and surgical instrumentation were performed as in previous experiments [4,15]. After induction of anesthesia with iv propofol and ketamine and subsequent endotracheal intubation, anesthesia was maintained with continuous iv propofol (6-8 mg kg -1 h -1 ) and remifentanil (15-20 lg kg -1 h -1 ).…”

Section: Surgical Preparationmentioning

confidence: 99%

“…Recombinant human erythropoietin (rhEPO) protected against spinal cord I/R injury [2,3], and, in fact, we previously showed in swine that 300 IU kg -1 rhEPO prior to aortic balloon occlusion and during early reperfusion reduced both thoracic spinal cord neuronal damage and glial apoptosis. Motor neuron function, however, did not recover, most likely due to the low dose of rhEPO administered and/or as a result of the marked tissue damage [4]. Moreover, Ehrenreich et al [5] recently reported a significantly higher overall death rate in rhEPO-treated patients with stroke, possibly as a result of the high number of patients undergoing systemic thrombolysis with recombinant tissue plasminogen activator: in vitro, a single rhEPO exposure enhances production of plasminogen activator inhibitor-1 [6].…”

Section: Introductionmentioning

confidence: 99%

“…All data on cEPOrelated organ protection against I/R injury, however, originate from nonresuscitated rodent models which did not integrate standard resuscitation measures such as fluid resuscitation and/or vasopressor support to guarantee wellmaintained systemic hemodynamics. Therefore, we tested the hypothesis that a newly developed carbamylated EPO-FC fusion protein, consisting of two EPO molecules fused to the FC part of IgG1 (cEPO-FC) [14], protects against ischemic spinal cord dysfunction and neuronal damage comparably to rhEPO in swine undergoing thoracic aortic balloon occlusion-induced I/R injury [4].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury

et al. 2011

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Section: Surgical Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury

et al. 2011

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“…Simon et al 13 reported that EPO, administered immediately before ischemia and additionally after reperfusion, did not improve neurological recovery following spinal cord ischemia. Forty-five minutes of aortic occlusion was applied to the swine for this study, and both EPO-treated and saline-treated animals presented totally paralyzed lower extremities with marked histological injury.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with erythropoietin attenuates the neurological injury after spinal cord ischemia

et al. 2011

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Study design: Experimental study. Objectives: To investigate the effect of erythropoietin (EPO) pretreatment on spinal cord ischemic injury. Setting: Experimental Research Center at Seoul National University Bundang Hospital, Korea. Methods: Rats were treated with either 1000 IU kg À1 of EPO (EPO group, n¼8) or saline (control group, n¼8) 24 h before ischemia. Spinal cord ischemia was induced using a balloon-tipped catheter placed on the proximal descending aorta in the control group and the EPO group, but not in the sham group (n¼8). Neurological function was assessed using the motor deficit index (MDI; 0¼normal, 6¼complete paralysis) until 7 days after reperfusion, and histological examination of spinal cord was performed. Results: At the first day after reperfusion, the EPO group demonstrated a significantly lower MDI compared with the control group (2.0 (0.3-2.0) vs 4.0 (3.0-4.8), median (interquartile range); EPO group vs control group, respectively; P¼0.002). This trend was sustained until 7 days after reperfusion (1.0 (1.0-1.8) vs 4.5 (3.3-5.0); EPO group vs control group, respectively; P¼0.001), and more normal motor neurons (29.9±3.1 vs 21.4±3.4, mean±s.d.; EPO group vs control group, respectively; Po0.001) were observed. However, compared with the sham group, the EPO group displayed a significantly higher MDI (0.0, sham group) and fewer intact motor neurons (37.8 ± 5.5, sham group; Po0.001, sham vs control group). Conclusion: Pretreatment with EPO significantly attenuates neurological injury following spinal cord ischemia, although it cannot completely abolish the ischemic injury.

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“…19,20 Briefly, mice were anesthetized using tribromoethanol, and rectal temperature was maintained at 37°C. For this purpose, three gold electrodes were inserted into the scalp and one into the soft palate to apply electric impulses (MultiPulse Stimulator D185-Mark, Digitimer LTD) to the motor cortex to quantify MEPs.…”

Section: Electrophysiologymentioning

confidence: 99%

Nrf2 Activation in Astrocytes Contributes to Spinal Cord Ischemic Tolerance Induced by Hyperbaric Oxygen Preconditioning

Huang

Zhang

et al. 2014

Journal of Neurotrauma

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In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/ reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtimepolymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, c-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury. HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in neurons. In conclusion, our findings demonstrated that spinal cord ischemic tolerance induced by HBO-PC may be mainly related to Nrf2 activation in astrocytes.

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Erythropoietin during porcine aortic balloon occlusion-induced ischemia/reperfusion injury

Abstract: During porcine aortic occlusion-induced ischemia/reperfusion erythropoietin improved kidney function and spinal cord integrity. The lacking effect on spinal cord function was most likely the result of the pronounced neuronal damage associated with the longlasting ischemia.

Cited by 41 publications

References 51 publications

Comparison of carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury

Comparison of carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury

Pretreatment with erythropoietin attenuates the neurological injury after spinal cord ischemia

Nrf2 Activation in Astrocytes Contributes to Spinal Cord Ischemic Tolerance Induced by Hyperbaric Oxygen Preconditioning

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