Uric acid protects against secondary damage after spinal cord injury

Gwen S. Scott, Salvatore Cuzzocrea, Tiziana Genovese, Hilary Koprowski, D. Craig Hooper

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Peroxynitrite contributes to the pathogenesis of various neurodegenerative disorders through multiple mechanisms and is thought to mediate secondary neuronal cell death after spinal cord injury (SCI). Here we establish that physiologically relevant levels of uric acid (UA), a selective inhibitor of certain peroxynitrite-mediated reactions, block the toxic effects of peroxynitrite on primary spinal cord neurons in vitro. Furthermore, administration of UA at the onset of SCI in a mouse model inhibits several pathological changes in the spinal cord including general tissue damage, nitrotyrosine formation, lipid peroxidation, activation of poly(ADP-ribose) polymerase, and neutrophil invasion. More importantly, UA treatment improves functional recovery from the injury. Taken together, our findings support the concept that peroxynitrite contributes to the pathophysiology of secondary damage after SCI. They also raise the possibility that elevating UA levels may provide a therapeutic approach for the treatment of SCI as well as other neurological diseases with a peroxynitrite-mediated pathological component.

Original languageEnglish
Pages (from-to)3483-3488
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number9
DOIs
StatePublished - 1 Mar 2005
Externally publishedYes

Keywords

  • Blood-brain barrier
  • Cytotoxicity
  • Neutrophils
  • Peroxynitrite
  • Spinal cord neurons

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