THE ENDOGENOUS ANTIOXIDANT GLUTATHIONE AS A FACTOR IN THE SURVIVAL OFPHYSICALLY INJURED MAMMALIAN SPINAL-CORD NEURONS

Glutathione is part of the system of cellular defenses against lipid p eroxidation and other free radical-mediated damage. An established in vitro trauma model was utilized to evaluate whether glutathione is a f actor in the survival of mammalian spinal cord neurons following physi cal injury. Cultured murine spinal neurons were subjected to a standar d lesion: transection of a primary dendrite 100 mu m from the perikary on. Prior reduction of glutathione with ethacrynic acid or buthionine sulfoximine caused a dose-dependent decrease in neuronal survival 24 h ours after dendrotomy. Prior glutathione augmentation with gamma-gluta mylcysteine or L-2-oxo-4-thiazolidine carboxylic acid significantly in creased survival, but N-acetyl-cysteine was not protective. Gamma glut amylcysteine effected the most rapid increase in glutathione (peak at 10 min), and survival was 72% +/- 10 when 0.2 mM gamma-glutamylcystein e was added immediately after dendrotomy compared with 38% +/- 4 in th e 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 p hase spinal cord injury (SCI) intervention strategy.