Uric acid protects against secondary damage after spinal cord injury.
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.
Scott
Gwen S
GS
Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Cuzzocrea
Salvatore
S
Genovese
Tiziana
T
Koprowski
Hilary
H
Hooper
D Craig
DC
D000818:Animals; D002478:Cells, Cultured; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D014527:Uric Acid / Q000494:pharmacology* / Q000627:therapeutic use
D030421:Peroxynitrous Acid; D014527:Uric Acid; D009195:Peroxidase
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