Effect of ethyl pyruvate against un-injurious spinal cord ischemia in rats

Introduction

Paraplegia is a complication that sometimes occurs after successful operations on the thoracic aorta with an incidence rate ranging from 0.9% to 40%. The primary cause of such spinal cord injury is ischemia. Pyruvate, a glycolytic intermediate, is a promising substance with a protective effect against ischemia. Its mechanism of action has been assumed to be an energy supply to augment the ATP level, and free radical scavenging. However, pyruvate is fragile in aqueous solution, and its use is thus restricted. Ethyl pyruvate (EP) is a novel ester derivative of pyruvate, which is stable in solution and dissolves immediately into pyruvate in blood. The objective of this study was to evaluate whether EP can improve the neurological outcome in a rat spinal ischemia/reperfusion model.

Methods

We used male Sprague-Dawley rats, and spinal cord ischemia was induced for 9 min, in which most rats tend to become paraplegic, using an intra-aortic balloon occlusion. EP was dissolved in saline under sonication with a final concentration of 28 mmol/l. We administered 2 ml EP solution pre and post ischemic interval. For the control, saline (vehicle fluid) was administered at the same times. The neurological function of the lower extremities was assessed with the BBB scale at 24 and 72 hours after ischemia. A histochemical examination of the spinal cord was performed for neurons or apoptotic bodies.

Results and discussion

The motor function of the lower extremities (BBB scale) of the EP group was better than the saline group at 24 and 72 hours after ischemia. The number of neurons stained for NeuN in the EP group was higher than those in the saline group, but less than the normal control (no treatment) (P < 0.001). The number of apoptotic bodies in the EP group was less than those in the saline group (P < 0.001). We demonstrated that the EP improved the neurological outcome after a transient ischemia and reperfusion model in rats. The histological findings supported the hypothesis that EP protected the neurons against ischemic injury. This is a first report to describe the neuroprotective effect of EP in vivo.

Conclusion

EP improved the neurological outcome after transient ischemia and reperfusion, and also preserved the neurons. Although the mechanism for such neuroprotection is still unclear, inhibition of apoptosis may be related its preventive effect against neuronal damage.