Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1998-10-29
|
| pubmed:abstractText |
Uric acid is a well-known natural antioxidant present in fluids and tissues throughout the body. Oxyradical production and cellular calcium overload are believed to contribute to the damage and death of neurons that occurs following cerebral ischemia in victims of stroke. We now report that uric acid protects cultured rat hippocampal neurons against cell death induced by insults relevant to the pathogenesis of cerebral ischemia, including exposure to the excitatory amino acid glutamate and the metabolic poison cyanide. Confocal laser scanning microscope analyses showed that uric acid suppresses the accumulation of reactive oxygen species (hydrogen peroxide and peroxynitrite), and lipid peroxidation, associated with each insult. Mitochondrial function was compromised by the excitotoxic and metabolic insults, and was preserved in neurons treated with uric acid. Delayed elevations of intracellular free calcium levels induced by glutamate and cyanide were significantly attenuated in neurons treated with uric acid. These data demonstrate a neuroprotective action of uric acid that involves suppression of oxyradical accumulation, stabilization of calcium homeostasis, and preservation of mitochondrial function. Administration of uric acid to adult rats either 24 hr prior to middle cerebral artery occlusion (62.5 mg uric acid/kg, intraperitoneally) or 1 hr following reperfusion (16 mg uric acid/kg, intravenously) resulted in a highly significant reduction in ischemic damage to cerebral cortex and striatum, and improved behavioral outcome. These findings support a central role for oxyradicals in excitotoxic and ischemic neuronal injury, and suggest a potential therapeutic use for uric acid in ischemic stroke and related neurodegenerative conditions.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Cyanide,
http://linkedlifedata.com/resource/pubmed/chemical/Uric Acid
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0360-4012
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
53
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
613-25
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9726432-Animals,
pubmed-meshheading:9726432-Calcium,
pubmed-meshheading:9726432-Cell Death,
pubmed-meshheading:9726432-Cells, Cultured,
pubmed-meshheading:9726432-Cerebral Cortex,
pubmed-meshheading:9726432-Glutamic Acid,
pubmed-meshheading:9726432-Hippocampus,
pubmed-meshheading:9726432-Ischemic Attack, Transient,
pubmed-meshheading:9726432-Lipid Peroxidation,
pubmed-meshheading:9726432-Male,
pubmed-meshheading:9726432-Membrane Potentials,
pubmed-meshheading:9726432-Microscopy, Confocal,
pubmed-meshheading:9726432-Mitochondria,
pubmed-meshheading:9726432-Neostriatum,
pubmed-meshheading:9726432-Neurons,
pubmed-meshheading:9726432-Neuroprotective Agents,
pubmed-meshheading:9726432-Oxidative Stress,
pubmed-meshheading:9726432-Rats,
pubmed-meshheading:9726432-Rats, Sprague-Dawley,
pubmed-meshheading:9726432-Reactive Oxygen Species,
pubmed-meshheading:9726432-Sodium Cyanide,
pubmed-meshheading:9726432-Uric Acid
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo.
|
| pubmed:affiliation |
Sanders Brown Research Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington 40536-0230, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|