The endogenous antioxidant glutathione as a factor in the survival of physically injured mammalian spinal cord neurons

被引:23
作者
Lucas, JH
Wheeler, DG
Emery, DG
Mallery, SR
机构
[1] Ohio State Univ, Dept Physiol, Coll Med, Columbus, OH 43210 USA
[2] Ohio State Univ, Coll Dent, Dept Oral Surg & Pathol, Columbus, OH 43210 USA
[3] Iowa State Univ, Dept Zool & Genet, Ames, IA 50011 USA
关键词
axotomy; CNS trauma; cell death; free radicals; lipid peroxidation; spinal cord injury; tissue culture;
D O I
10.1097/00005072-199810000-00006
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Glutathione is part of the system of cellular defenses against lipid peroxidation and other free radical-mediated damage. An established in vitro trauma model was utilized to evaluate whether glutathione is a factor in the survival of mammalian spinal cord neurons following physical injury. Cultured murine spinal neurons were subjected to a standard lesion: transection of a primary dendrite 100 mu m from the perikaryon. Prior reduction of glutathione with ethacrynic acid or buthionine sulfoximine caused a dose-dependent decrease in neuronal survival 24 hours after dendrotomy. Prior glutathione augmentation with gamma-glutamylcysteine or L-2-oxo-4-thiazolidine carboxylic acid significantly increased survival, but N-acetyl-cysteine was not protective. Gamma glutamylcysteine effected the most rapid increase in glutathione (peak at 10 min), and survival was 72% +/- 10 when 0.2 mM gamma-glutamylcysteine was added immediately after dendrotomy compared with 38% +/- 4 in the control group (p < 0.0001). These results indicate that the level of glutathione is a factor in spinal cord neuron survival after physical trauma, and that glutathione augmentation may be an effective acute phase spinal cord injury (SCI) intervention strategy.
引用
收藏
页码:937 / 954
页数:18
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