Recombinant Human Erythropoietin In Rats With Acute Nerve Protective Effect And Mechanism Of Traumatic Brain Injury

Objective:To investigate the effect of recombinant human erythropoietin(rhEPO) on MMP-9and AQP-4expression in the rats’brain tissue of the injury after acute traumatic brain injury and to explore its neuroprotective effect mechanism.Methods:Fifty-five healthy adult male SD rats (250-350g)were randomly dividied into sham operation group (n=5), control group (n=25) and the EPO treatment group (n=25). The traumatic brain injury of the latter two groups was induced by Feeney’s.the sham operation group only emerged the dura but not injury.rhEPO treatment group underwent intraperitoneal injection of5000U/kg rhEPO after the injury.In the control group and sham operation group in the time point to give equal normal saline.The rats in the control group and the EPO treatment group were redivided into5subgroups (6h、24h、48h、3d、7d groups)of5rats each respectively according to different time after the injury.Model making a success, the nerve functional score.Under10%cholralhydrate anesthesia,the rats was disposeded at6h,24h,48h,3d and7d after the injury.The histology was detected by the HE staining and the expression of MMP-9and AQP-4was detected by immuno histochemical.Results:1.Neurobehavioral evaluation:After the brain injury,the rats immediately appeared grasp whole, forelimb flexion and hindlimb stiffness,increased muscle tone,inability to walk straight,increased to a side and so on.Conscious spiritual malaise and reduced its activities existed. Postoperative neurological scores are in7to12points in between.2.Histological observation:cellular edema appeared at6h after the injury in lesions. Brain edema became much more severe over time.The karyopyknosis and dark cell can be observed at48h after injury.The edema can be seen at72h after injury, but the number was lower than that at24h and glial cells’proliferation was higher than obvious; At7d edema nearly disappeared,glial cell proliferation was not evident after injury and the the number of dark cell decreased.3.Immunohistochemical analysis:The expression of MMP-9in the brain tissue of the injury appeared6hours (51.82±4.62) after trauma,reached its peak at48th (83.51±9.61) and was significantly higher in the injury group than that in the sham operation group(P<0.05).The expression of AQP-4increased in TBI model group from6h (42.18±12.78), reached its peak at24h (55.28±9.88) and was significantly higher in the injury group than that in the sham operation group(P<0.05).The expression was significantly lower in rhEPO treatment group than that in control group(P<0.05).Conclusion:Recombinant humam erythropoietin can reduce cerebral cortex in brain tissue damage MMP-9and AQP-4expression,reduce inflammation and the occurrence of edema and play a neural protection after rats acute traumatic brain injury.