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 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.
Chikawa
T
T
Department of Orthopedic Surgery, School of Medicine, the University of Tokushima, Japan.
Ikata
T
T
Katoh
S
S
Hamada
Y
Y
Kogure
K
K
Fukuzawa
K
K
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009187:Myelitis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D020933:Neurotrophin 3 / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics; D010713:Phosphatidylcholines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology
D007375:Interleukin-1; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D010713:Phosphatidylcholines; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D018799:Intercellular Adhesion Molecule-1; D005993:Glycerolphosphate Dehydrogenase; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D008775:Methylprednisolone