Erythropoietin's Neuroprotective Mechanisms In Spinal Cord Ischemia-reperfusion Injury

Objectives: Ischemia-reperfusion of spinal cord is a common injury. It always results in severely motorial and sensory dysfunction, which will brying heavy burden to the patient's family and society. At present, more and more importance have been attached to improve the neurological outcome of patients suffered from this kind of injury. Many Researches had demonstrated that apoptosis of neurons or glia cells was a key factor of ischemia-reperfusion injury in spinal cord. Therefore, rescueing measures aimed to decrease apoptosis of never cells may bring a hopeful treatment for spinal cord injury. Many kinds of drugs such as anti-oxidants and blockers of Ca2+ channel have been developed to protect or rescue the dying neural cells caused by ischemia-reperfusion, but there still has no satisfying outcome. Recently, erythropoietin received much attention because that there are evidences that erythropoietin had a protective effect in central nervous system (CNS). Many researches have showed that erythropoietin is a promising agent on neuroprotection. In this experiment, animal models of spinal cord ischemia-reperfusion injury were established in rats and rabbits, and the effect of recombinant human erythropoietin on neurological function was observed.The purpose of our experiment is to study the. Neuroprotective mechanisms of erythropoietin after spinal cord injury resulted from ischemia-reperfusion Methods 1. Twenty rats were selected to establish the models of spinal cord ischemia-reperfusion injury, and the expressions of EPO mRNA and EPOR mRNA were detected by RT-PCR and immuno-fluolo-histochemistry. 2. Twenty-four rabbits were selected to establish the models of spinal cord ischemia-reperfusion injury, and the effect of recombinant human erythropoietin (rhEPO) on neuroprotection was evaluated through functional recovery. 3. The apoptosis of neural cells in spinal cord were examined by TUNEL method. 4. The expression of bcl-2 and Bax in intact spinal cord and injured spinal cord of rabbits was examined by immuno-fluolo-histochemistry. Results 1. Animal models of spinal cord ischemia-reperfusion injury were established in rats successfully. Forty-eight hours after injury, the expression of EPO and EPOR in the injured spinal cord increased by 61.7% and 150.9% respectively than that in intact spinal cord. 2. Animal models of spinal cord ischemia-reperfusion injury were established in rabbits successfully. The results showed that application of recombinant human erythropoietin could reduce the neurological loss significantly. 3. The apoptosis of neural cells in spinal cord reduced significantly after rhEPO was applied to rabbits of spinal cord ischemia-reperfusion injury. 4. The level of bcl-2 mRNA had increased significantly while the the level of bax mRNA had decreased obviously after the the exterior EPO were applied to the rabbits suffering with spinal cord ischemia-reperfusion injury. Conclusions 1. EPO and EPOR do exist in spinal cord. The expression of EPOR increases significantly in the condition of spinal cord ischemia-reperfusion injury. 2. The exterior EPO can enhance the tolerance of neural cells in spinal cord against the ischemia-reperfusion injury. The exterior EPO can protect the injured spinal cord in a certain extent and improved the neurological function in animals of SCIRI. 3. The apoptosis of neural cells plays a key role during the course of SCIRI. However, exterior EPO can reduce the apoptosis of neural cells caused by SCIRI. 4. The mechanisms of EPO rescuing neural cells from apoptosis caused by SCIRI may be that EPO could up-regulat the level of bcl-2 and down-regulat the level of bax.