Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits.

Bingbing Liu,Zhengyuan Xia,Weihua Huang,Songmei Ma,Xiaoshan Xiao,Yao Xu

doi:10.1155/2015/624819

Abstract

Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties.

Highlights

Spinal cord injury is mainly divided into primary and secondary injuries according to pathophysiologic features
The present study showed that ulinastatin improved the neurological outcome and reduced the postischemic apoptotic cell death in neurons by way of decreasing the levels of MDA, increasing superoxide dismutase (SOD) activities, suppressing the upregulation of the proapoptotic protein expression and the downregulation of antiapoptotic protein expression
The primary injury followed by blood reperfusion may cause additional spinal cord damage, which impairs neuron function and generates the secondary damage

Summary

Introduction

Spinal cord injury is mainly divided into primary and secondary injuries according to pathophysiologic features. The secondary injury often takes place in the process of perfusion after spinal cord ischemia, causing spinal cord ischemia-reperfusion injury (SCIRI) which aggravates the neurofunctional damages of limbs. Spinal cord ischemiareperfusion injury remains to be a devastating complication of thoracic aortic intervention, which may cause delayed paraplegia [2, 3]. Technological advancements in surgery, such as hypothermic circulatory arrest, left heart bypass, intercostal artery reimplantation, and lumbar drains, have partly reduced complications of spinal cord injury, the incidence of paraplegia (immediate and delayed combined) after thoracic aortic intervention still ranges between 4% and 11% [4, 5].

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