10-21-2001, 12:56 PM
Chikawa T, Ikata T, Katoh S, Hamada Y, Kogure K and Fukuzawa K (2001). Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats: transcriptional regulation of inflammatory and neurotrophic genes. J Neurotrauma. 18 (1): 93-103. Summary: The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpredisolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindlimb motor function and expression of mRNA of pro- inflammatory and neurotrophic genes. Hindlimb motor function was assessed as the BBB open field locomotor 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-SOD 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-SOD group increased, whereas that of the MP group showed a temporary decrease from day 3 to 5 and then it gradually recovered. The scores in all groups reached a plateau about 18 days after SCI. The PC-SOD+MP group did not show a synergism but a tendency similar to that of the MP group. PC-SOD and MP had down-regulatory effects on mRNA expression of pro-inflammatory substances such as interleukin-1beta [IL-1beta), intercellular adhesion molecule-1 [ICAM-1), and inducible-nitric oxide synthetase [i-NOS) after spinal cord compression at 3, 6, and 24 h, respectively, as judged by a semiquantitative reverse transcription- polymerase chain reaction and on the lipid peroxide [LPO) level 1 h after injury as determined by thiobarbituric acid-reactive substances. The suppression of pro-inflammatory genes expression, especially IL- 1beta were greater in the MP group than in the PC-SOD group, while suppression of LPO level was similar in these two groups. PC-SOD+MP treatment augmented the suppression of all three pro-inflammatory genes expression 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 mRNA level was enhanced by PC-SOD treatment, but not by MP treatment. Thus, the effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOD. The difference in motor function in the early and later stage may be partially due to differences in expression of IL-1beta and NT-3 after either treatment, through an IL-1beta-dependent or NT-3-mediated repair response. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11200253> Department of Orthopedic Surgery, School of Medicine, the University of Tokushima, Japan.