Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death: a site of the neuroprotective action of methylprednisolone

The present study explores in vivo whether and how prostaglandin F-2 alpha (PGF(2 alpha)), a membrane phospholipid hydrolysis product, causes neuronal death. The concentration of PGF(2 alpha) measured by microdialysis samplin g increased threefold immediately following impact injury to the rat spinal cord. Administration of PGF(2 alpha) into the cord through a dialysis fibe r caused significant cell loss, increased extracellular levels of hydroxyl radicals and malondialdehyde - an end product of membrane lipid peroxidatio n - to 3.3 and 2.3 times basal levels, respectively. This suggests that PGF (2 alpha)-induced cell death is partly due to hydroxyl radical-triggered pe roxidation. Generating hydroxyl radical by administering Fenton's reagents into the cord through the fibers significantly increased malondialdehyde pr oduction the first direct in vivo evidence that hydroxyl radical triggers m embrane lipid peroxidation. Methylprednisolone significantly reduced the re lease of PGF(2 alpha) upon spinal cord injury and blocked PGF(2 alpha)-indu ced hydroxyl radical and malondialdehyde production, but did not significan tly reduce Fenton's reagent-induced malondialdehyde production, despite the production of more malondialdehyde by PGF(2 alpha). This suggests that met hylprednisolone may not directly scavenge hydroxyl radical, and that its 'a ntioxidant' effect is a consequence of blocking the pathways for producing toxic PGF(2 alpha) and for PGF(2 alpha)-induced hydroxyl radical formation, thereby reducing membrane lipid peroxidation.