Reducing postischemic paraplegia using conjugated superoxide dismutase

Agee, Jon; Flanagan, Terry L.; Blackbourne, Lorne H.; Krön, Irving L.; Tribble, Curtis G.

doi:10.1016/0003-4975(91)91004-f

Cited by 81 publications

(27 citation statements)

References 16 publications

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“…Collective clamping of the great vessels produced spinal cord ischemia in the rabbits and after 40 min all control animals were rendered paraplegic [9,22]. Moreover, the reliability and reproducibility of this procedure were good as previously reported [1].…”

Section: Methodssupporting

confidence: 52%

The Penile Erection Efficacy of a New Phosphodiesterase Type 5 Inhibitor, Mirodenafil (SK3530), in Rabbits with Acute Spinal Cord Injury

Jung

Kim

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury. KEY WORDS: mirodenafil, penile erection, phosphodiesterase inhibitor, SK3530, spinal cord injury.J. Vet. Med. Sci. 70(11): 1199-1204, 2008 The advent of phosphodiesterase type 5 (PDE5) inhibitors as oral therapy for erectile dysfunction (ED) ushered in a revolution in clinical management of this condition. Oral ED medications influence the complex neurological, vascular and humoral process underlying penile erection. PDE5 inhibitors influence local regulatory mechanisms of erection, potentiating the smooth muscle relaxing effects of nitric oxide (NO) on resistance arteries and trabecular smooth muscle within the corpus cavernosum [4].Across the world, approximately 152 million men have ED, including about 31 million men in Europe and 18 million men in the US [6,24]. With anticipated increases in the median ages of Western industrialized societies and population growth in developing nations, the number of cases is projected to increase by about 170 million worldwide over the next 25 years. A wide variety of treatment options are now available for patients with ED, ranging from hormone replacement, counseling, non-invasive devices and oral therapies to injectable agents, penile implants and vascular surgery. As a result, almost all men with ED of any type can receive effective treatment. The process of care model designates counseling, vacuum pump, and PDE 5 inhibitors such as sildenafil as first-line options for ED in the primary care s...

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Section: Methodssupporting

confidence: 52%

The Penile Erection Efficacy of a New Phosphodiesterase Type 5 Inhibitor, Mirodenafil (SK3530), in Rabbits with Acute Spinal Cord Injury

Jung

Kim

et al. 2008

The Journal of Veterinary Medical Science

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“…In a recent report, only 5% of 127 patients who underwent clamp/sew surgery developed paraplegia [3] ; paraplegia caused by ISCI remains a problem that should be solved. Multiple studies have suggested that calcium overload, inflammatory processes, free radical production, platelet aggregation, neutrophil accumulation and adhesion following ischemia might contribute to the neuronal damage that was observed in patients with ISCI [4,5] . However, the cellular and molecular mechanisms of ischemic spinal cord injury are not fully understood.…”

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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“…FORs cause cellular injury by inducing lipid peroxidation [8] . Therefore, the prevention of oxidative stress-induced lipid peroxidation in spinal tissue seems to be an important goal with respect to protecting the SC from I/R injury [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Methylene Blue Decreases Ischemia-Reperfusion (I/R)-Induced Spinal Cord Injury: An in vivo Study in an I/R Rabbit Model

Bardakçi¹,

Kaplan²,

Karadeniz³

et al. 2006

Eur Surg Res

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Objectives: To evaluate the effects of intravenous methylene blue (MB) administration on ischemia-reperfusion (I/R) injury of the spinal cord (SC). Methods: 16 rabbits were randomly assigned either to group M (n = 8; receiving MB, intervention group) or group C (n = 8; control group) and underwent a 30-min period of SC ischemia by clamping the abdominal aorta between the left renal artery and the aortic bifurcation. 15 min before clamping, rabbits received either intravenous MB (10 mg/kg; group M) or normal saline (group C). The two groups were compared 24 h postoperatively both histologically and for neurological function, using a Tarlov score. Measurements to determine levels of malondialdehyde (MDA) and glutathione (GSH) in the SC tissue were also performed. Results: Neurological impairment and spinal tissue MDA levels were significantly lower in animals treated with MB (p < 0.001). In contrast, spinal GSH levels were significantly higher in group M (p < 0.001). Histological examination revealed that the integrity of the SC was better preserved in the MB group, whereas cords from the control group exhibited evidence of acute neuronal injury. Conclusions: The prophylactic use of MB reduces neurological injury and improves clinical outcomes in the rabbit SC I/R model. These effects are probably mediated by the drug’s antioxidant properties.

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Reducing postischemic paraplegia using conjugated superoxide dismutase

Cited by 81 publications

References 16 publications

The Penile Erection Efficacy of a New Phosphodiesterase Type 5 Inhibitor, Mirodenafil (SK3530), in Rabbits with Acute Spinal Cord Injury

The Penile Erection Efficacy of a New Phosphodiesterase Type 5 Inhibitor, Mirodenafil (SK3530), in Rabbits with Acute Spinal Cord Injury

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

Methylene Blue Decreases Ischemia-Reperfusion (I/R)-Induced Spinal Cord Injury: An in vivo Study in an I/R Rabbit Model

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