Activated Protein C Reduces the Ischemia/Reperfusion-Induced Spinal Cord Injury in Rats by Inhibiting Neutrophil Activation

Hirose, K; Okajima, Kenji; Taoka, Yuji; Uchiba, Mitsuhiro; Tagami, Hirofumi; Nakano, K.; Utoh, Junichi; Okabe, Hiroaki; Kitamura, Nobuo

doi:10.1097/00000658-200008000-00018

Cited by 130 publications

(121 citation statements)

References 39 publications

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“…28 Free radicals stimulate monocytes to produce various cytokines such as IL-1, and TNF-a. 29 These cytokines act on endothelial cells to promote the production of interleukins (IL-2, IL-4, IL-6 and IL-8). IL-6 is a major stimulus of acute-phase response and is also responsible for the respiratory burst of neutrophils and release of free radicals.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that antagonism of neutrophil adherence to endothelium by means of monoclonal antibodies or platelet activating factor antagonist reduced spinal cord injury after transient ischemia in animal models. 3,22,29 PTX is a Figure 3 Boxplot of the MDA levels of each group of animals. Horizontal bars represent the 90th, 75th, 50th (median), 25th, and 10th percentiles Figure 4 Boxplot of the SOD levels of each group of animals.…”

Section: Discussionmentioning

confidence: 99%

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Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal cord injury in rabbits

et al. 2002

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Study design: Occlusion of the infrarenal abdominal aorta with administration of pentoxifylline was applied to adult rabbits, followed by removal of aortic clamp and reperfusion. Tissue levels of cytokines, lipid peroxides, and antioxidant enzymes were assayed and compared within groups. Objectives: To examine the e ect of pentoxifylline (PTX) on cytokine levels, lipid peroxidation, and antioxidant enzymes in a rabbit model of spinal cord ischemia-reperfusion injury induced by aortic occlusion. Setting: Isparta, Turkey. Methods: Rabbits were randomly allocated into four groups of sham laparotomy (SHAM), sham laparotomy with PTX administration (SHAM+PTX), aortic occlusion and reperfusion (AOR), aortic occlusion and reperfusion with PTX administration (AOR+PTX). An intravenous bolus of 50 mg/kg PTX was given just before aortic cross clamping. An atraumatic microvascular clamp was then placed on the abdominal aorta immediately distal to the left renal artery for 30 min. PTX was infused at a rate of 0.5 mg/kg/min during the aortic occlusion. Animals were subjected to 120 min of reperfusion after removal of the aortic clamp. All animals were sacri®ced at the end of reperfusion. The lumbosacral segments of spinal cords were quickly harvested and stored at 7788C for biochemical assays of IL-6, TNF-a, MDA, SOD, and CAT levels. Di erences among groups were analyzed by one-way analysis of variance followed by a post hoc Tukey's honestly signi®cant di erence test. Results: No di erences in mean levels of IL-6, TNF-a, MDA, SOD, and CAT were noted between SHAM and SHAM+PTX groups (P40.05). There was a signi®cant increase in all biochemical parameters in the AOR group (P50.05). Administration of PTX signi®cantly attenuated the levels of all biochemical parameters in the AOR+PTX group (P50.05). Conclusion: PTX pretreatment attenuated ischemia-reperfusion induced spinal cord injury in a rabbit model, in terms of biochemical parameters of ischemia and reperfusion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal cord injury in rabbits

et al. 2002

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“…The motor functions of the rats were assessed at 24 h, 48 h, and 72 h after the procedure using the following modified Tarlov scale [6,17,18] : 0, no voluntary movement (complete paraplegia); 1, perceptible movement at the joint; 2, good joint mobility but unable to stand; 3, ability to stand but unable to walk; 4, weak walking; 5, complete recovery.…”

Section: Neurological Assessmentmentioning

confidence: 99%

“…Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) are key proinflammatory cytokines that play important functions in the central nervous system during inflammatory injury. Besides causing direct damage to cell membranes, free oxygen radicals activate the accumulation of neutrophils and stimulate various types of cells to produce TNF-α and IL-1β [6] . These cytokines further contribute to the production of other cytokines and to the expression of endothelial leukocyte adhesion factor-1, ultimately leading to endothelial cell damage and spinal cord ischemia [7,8] .…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

Gong

Yuan

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process. Methods: Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia. The motor functions of the animals were assessed according to the modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2-L4) was taken out for histopathological examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA. Results: Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores, and reduced the number of apoptotic neurons, which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level correlated well with the serum TNF-α, IL-1β and IL-6 levels during the time period of reperfusion. Conclusion:The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1.

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“…Neutrophil adhesion to endothelial cells is inhibited by APC (Received in original form January 27, 2005; accepted in final form February 25, 2005) Supported by grants P01 HL68743 and M01 RR0051 from the National Institutes of Health and Eli Lilly and Company. (13). Recent studies show that neutrophils and monocytes have receptors that interact with protein C, APC, and rhAPC (14).…”

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confidence: 99%

Effects of Recombinant Human Activated Protein C in Human Models of Endotoxin Administration

Abraham¹

2005

Proceedings of the American Thoracic Society

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Alterations in the generation of activated protein C (APC) as well as in the interactions of APC with the endothelial protein C receptor are present in severe sepsis and acute lung injury. Administration of recombinant human activated protein C (rhAPC) improves the survival of critically ill patients with sepsis, but the mechanisms by which rhAPC produces benefit are not well defined. Human models of systemic and pulmonary endotoxin exposure may provide important insights into the mechanisms of action of rhAPC in critical illness. In volunteers given systemic endotoxin, rhAPC had minimal effects on physiologic parameters, including blood pressure, markers of inflammation, and measures of sepsis-induced coagulopathy. In contrast, in the setting of pulmonary endotoxin exposure, rhAPC decreased neutrophil migration into the airspaces and also diminished neutrophil chemotaxis. Administration of rhAPC did not affect other parameters of neutrophil function, including kinase activation, production of proinflammatory cytokines, or apoptosis. Such results indicate that the effects of rhAPC in inhibiting the infiltration of neutrophils into the lungs and other inflammatory sites may contribute to its beneficial effects in sepsis.

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Activated Protein C Reduces the Ischemia/Reperfusion-Induced Spinal Cord Injury in Rats by Inhibiting Neutrophil Activation

Cited by 130 publications

References 39 publications

Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal cord injury in rabbits

Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal cord injury in rabbits

Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

Effects of Recombinant Human Activated Protein C in Human Models of Endotoxin Administration

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