Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death

A site of the neuroprotective action of methylprednisolone

Danxia Liu, Liping Li, Lezel Augustus

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The present study explores in viva whether and how prostaglandin F (PGF), a membrane phospholipid hydrolysis product, causes neuronal death. The concentration of PGF measured by microdialysis sampling increased three-fold immediately following impact injury to the rat spinal cord. Administration of PGF 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 PGF-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 viva evidence that hydroxyl radical triggers membrane lipid peroxidation. Methylprednisolone significantly reduced the release of PGF upon spinal cord injury and blocked PGF-induced hydroxyl radical and malondialdehyde production, but did not significantly reduce Fenton's reagent-induced malondialdehyde production, despite the production of more malondialdehyde by PGF. 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 PGF and for PGF-induced hydroxyl radical formation, thereby reducing membrane lipid peroxidation.

Original languageEnglish (US)
Pages (from-to)1036-1047
Number of pages12
JournalJournal of Neurochemistry
Volume77
Issue number4
DOIs
StatePublished - 2001

Fingerprint

Dinoprost
Methylprednisolone
Cell death
Malondialdehyde
Spinal Cord Injuries
Hydroxyl Radical
Prostaglandins
Cell Death
Membrane Lipids
Lipid Peroxidation
Dialysis
Fibers
Poisons
Microdialysis
Rats
Cause of Death
Hydrolysis
Phospholipids
Spinal Cord
Antioxidants

Keywords

  • Hydroxyl radical
  • Malondialdehyde
  • Membrane phospholipid hydrolysis and peroxidation
  • Methylprednisolone
  • PGF
  • Secondary spinal cord injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death : A site of the neuroprotective action of methylprednisolone. / Liu, Danxia; Li, Liping; Augustus, Lezel.

In: Journal of Neurochemistry, Vol. 77, No. 4, 2001, p. 1036-1047.

Research output: Contribution to journalArticle

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