Role Of Estrogen In Regulating Reactive Oxygen Species After Acute Spinal Cord Injury

Objective:To investigate therapeutic effect and mechanism of neuroprotection of estrogen after acute spinal cord injury by designing moderate models of spinal cord injury in Sprague-Dawley rats.That was completed by using the BBB scoring system and detecting levels of oxidative stress.Methods:65 male rats were randomly divided into three groups:sham-group, estrogen-group,and control-group.These groups were divided into five subgroups at 6h,1d,1d,3d,5d,and 7d post-injury.The sham-group rats consisted of 3 rats in each subgroup.There were 5 rats in the five subgroups in both estrogen-group and control-group.Sham-group animals only received a laminectomy at T10 without injury.Injured rats received both laminectomy and 50 gram centimeter force SCI with the Allen's method.Estrogen-group received 4mg/kg estrogen at 15min post-injury; Control-group received equal volumes of 0.9%NS at the same time point.All drugs were delivered by intramuscular.All animals were evaluated for hindlimb locomotor changes by the BBB score at 1d,3d,5d,and 7d post-injury.Experimental rats were sacrificed at the five time points post-injury,and the lesion areas of the spinal cord were excised.Activities of superoxide dismutase(SOD),nitric oxide synthase(NOS),Hydrogen peroxide(H₂O₂),anti-superoxide anion,and anti-hydroxyl radical were examined with the chemical colorimetry.Results:BBB score in estrogen-group was significantly higher than in control-group at the time points of 1d,3d,5d,7d after injury.Activities of SOD in estrogen-group were significantly higher compared with in control-group at the time points of 1d,3d, 5d after injury,and reached the peak on day 5.Activities of SOD in control-group rose obviously by day 7.Activities of TNOS in both estrogen-group and control-group were increased significantly on day 5 compared with sham-group,but no differences between the two groups.Activities of TNOS were significantly decreased in estrogen-group than in control-group,but was higher than sham on day 7. Activities of iNOS in both estrogen-group and control-group were significantly increased compared with sham,but no differences between the two groups,iNOS were decreased significantly in estrogen-group but that in control rose further,there were obvious differences between the two groups on day 7.Capacities of anti-superoxide anion in estrogen-group were higher than in control,but were lower than sham on day 1.Capacities of anti-superoxide anion in control were higher compared with in estrogen and sham on day 7,no differences between estrogen and sham.Concentrations of H₂O₂ in estrogen were obviously higher than control at the time points of 1d,3d,5d,7d,and peaked twice on day 1 and 5,back to the levels of sham on day 7,that were low levels in control on day 7.Capacities of anti- hydroxyl radical in estrogen showed significant differences from in control at the time points of 6h,1d,5d,and reached their peak in estrogen on day 5,in control on day 1.Conclusions:Early administration of high-dose estrogen treatment promoted the nerve function of SD rats recovery after ASCI.Generations of ROS were increased early after injury.Oxidative stress participated in the progression of pathophysiological in the secondary lesions.Anti-oxidant system showed compensatory rise,which occurred late and function limited after SCI,however, estrogen treatment can advance and amplify this compensatory response.NOS activities were influenced not well-obviously in the late stage by estrogen treatment. Activities or capacities of part members of anti-oxidant system changed and distributed in a inconsistent way,which suggested the path of ROS was a progression consisted of time and multi-factors.Estrogen improved spinal cord damage following the initial injury through increasing capacities of anti-oxidant system to attenuate indirectly generations of ROS.