Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats: Transcriptional regulation of inflammatory and neurotrophic genes

The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpred isolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindl imb motor function and expression of mRNA of pro-inflammatory and neurotrop hic genes. Hindlimb motor function was assessed as the BBB open field locom otor scores. The BBB scores of three groups treated with either PC-SOD (40, 000 units/kg), MP (30 mg/kg), or a combination of PC-SOB and MP (PC-SOD+MP) increased with time until 3 days after SCI, and were significantly higher than that of the control group (p < 0.05). Thereafter, the score of the PC- SOB group increased, whereas that of the MP group showed a temporary decrea se from day 3 to 5 and then it gradually recovered. The scores in all group s reached a plateau about 18 days after SCI. The PC-SOD+MP group did not sh ow a synergism but a tendency similar to that of the MP group. PC-SOB and M P had down-regulatory effects on mRNA expression of pro-inflammatory substa nces such as interleukin-1<beta> (IL-1 beta), intercellular adhesion molecu le-1 (ICAM-1), and inducible-nitric oxide synthetase (i-NOS) after spinal c ord compression at 3, 6, and 24 h, respectively, as judged by a semiquantit ative reverse transcription-polymerase chain reaction and on the lipid pero xide (LPO) level 1 h after injury as determined by thiobarbituric acid-reac tive substances. The suppression of pro-inflammatory genes expression, espe cially IL-1 beta, were greater in the MP group than in the PC-SOB group, wh ile suppression of LPO level was similar in these two groups. PC-SOD+MP tre atment augmented the suppression of all three pro-inflammatory genes expres sion and the decrease of the LPO level. The level of neurotrophin-3 (NT-3) mRNA increased from 6 h after SCI and reached a maximum after 48 h. NT-3 mR NA level was enhanced by PC-SOB treatment, but not by MP treatment. Thus, t he effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOB. The difference in motor function in the early and later stage may be partially due to differences in expression of IL-1 beta and NT-3 after either treatment, through an IL-1 beta -dependent or NT-3-m ediated repair response.