| Objective:1. To investigate the effects of progesterone on cell apoptosis in early spinal cord injured (SCI) rats.2. To investigate the effects of early application of progesterone combined with body weight support treadmill training on motor function, morphology and expression of brain derived neurotrophic factor mRNA in spinal cord injured rats.Methods:1. Sixty male Sprague-Dawley rats were randomly divided into the sham-operation group, injury group and progesterone group. The model of SCI rat was made by modified Allen's contusion method. Five injections of 16mg/kg progesterone were given at 1,6,24,48 and 72h post-lesion by intraperitoneal. All the rats were sacrificed at 6,24,48 and 75h respectively after SCI. The lesion areas of spinal cord were dissected for morphological study by HE staining. The expression of caspase-3 was detected with immunohistochemistry method. Cell apoptosis was examined by TUNEL method.2. One hundred and twenty male Sprague-Dawley rats were randomly divided into the sham-operation group, model group, progesterone group, body weight support treadmill training(BWSTT)group and joint group(progesterone+BWSTT). There were thirty rats in each of the former three groups (1, 3, 7, 14, 21, 28d of six subgroups, five rats each) and fifteen rats in each of the latter two groups (14, 21, 28d of three subgroups, five rats each ). The model of SCI rat was made by modified Allen's contusion method. Five injections of 4mg/kg progesterone were given at 30min, 6, 24, 48 and 72h post-lesion by intraperitoneal. Body weight support treadmill training started one week after SCI and continued for 14 days.At different time points after spinal cord injury, we evaluated the function changes by Basso-Beattie-Bresnahan scales, observed the morphological changes by HE staining and detected the expression of BDNF mRNA through RT-PCR methods.Results:1. The sham-operation group displayed the normal histology morphous and there were few tunnel-positive cells and caspase-3 positive cells. Compared with the injured group , the apoptotic index and the amount of caspase-3 positive cells of the progesterone group decreased significantly at 6, 24, 48and 75h respectively after SCI.2. Both progesterone and BWSTT were able to facilitate the recovery of motor function of hindlimb and promote absorption of hematoma and nerve regeneration after spinal cord injury due to their synergistic effects. The RT-PCR results showed the expression of BDNF mRNA was consistently low in sham operation group, while it increased within three days in model group. In progesterone group, it was high in the first week and reached the peak at the 3rd day. In addition, it increased significantly from the 14th day and remained at high level even in one week after the termination of BWSTT in BWSTT group. It was higher in joint group than that in progesterone or BWSTT group (P<0.01).Conclusion:1. Inhibition of cell apoptosis after spinal cord injury in rats may be one of the neuroprotective mechanisms of progesterone.2. Early application of progesterone and body weight support treadmill training are able to facilitate the recovery of motor function in spinal cord injured rats. One possible reason may be that the progesterone and BWSTT which up-regulate BDNF mRNA of focal organization can promote nerve regeneration. Meanwhile, the performance with the combination of progesterone and BWSTT is superior to that with either single one.
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