Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death: a site of the neuroprotective action of methylprednisolone
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 77, Issue 4, pages 1036–1047, May 2001
How to Cite
Liu, D., Li, L. and Augustus, L. (2001), Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death: a site of the neuroprotective action of methylprednisolone. Journal of Neurochemistry, 77: 1036–1047. doi: 10.1046/j.1471-4159.2001.00306.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Resubmitted manuscript received February 12, 2001; accepted February 13, 2001.
- hydroxyl radical;
- membrane phospholipid hydrolysis and peroxidation;
- secondary spinal cord injury
The present study explores in vivo whether and how prostaglandin F2α (PGF2α), a membrane phospholipid hydrolysis product, causes neuronal death. The concentration of PGF2α measured by microdialysis sampling increased threefold immediately following impact injury to the rat spinal cord. Administration of PGF2α into the cord through a dialysis fiber caused significant cell loss, increased extracellular levels of hydroxyl radicals and malondialdehyde – an end product of membrane lipid peroxidation – to 3.3 and 2.3 times basal levels, respectively. This suggests that PGF2α-induced cell death is partly due to hydroxyl radical-triggered peroxidation. Generating hydroxyl radical by administering Fenton's reagents into the cord through the fibers significantly increased malondialdehyde production – the first direct in vivo evidence that hydroxyl radical triggers membrane lipid peroxidation. Methylprednisolone significantly reduced the release of PGF2α upon spinal cord injury and blocked PGF2α-induced hydroxyl radical and malondialdehyde production, but did not significantly reduce Fenton's reagent-induced malondialdehyde production, despite the production of more malondialdehyde by PGF2α. This suggests that methylprednisolone may not directly scavenge hydroxyl radical, and that its ‘antioxidant’ effect is a consequence of blocking the pathways for producing toxic PGF2α and for PGF2α-induced hydroxyl radical formation, thereby reducing membrane lipid peroxidation.