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Age influence on oxidative events during brain ischemia/reperfusion
1Molecular Toxicology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, U.S.A.
Archives of Gerontology and Geriatrics
|March 1, 1991
Summary
Ischemia/reperfusion injury causes oxidative brain damage, particularly in older gerbils. The spin-trapping agent PBN protects against this injury, suggesting a potential therapeutic target for brain protection.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Oxidative damage significantly impacts brain function, especially following disruptions like ischemia/reperfusion.
- Iron is a key catalyst in oxidative damage within brain homogenates.
- Ischemia/reperfusion insult (IRI) in the brain leads to protein oxidation and impaired glutamine synthetase activity.
Purpose of the Study:
- To investigate the occurrence and mechanisms of oxidative events in the ischemic/reperfusion-lesioned gerbil brain.
- To explore the relationship between IRI, glutamine synthetase activity, and excitotoxicity.
- To determine the protective effects of alpha-phenyl-tert-butyl nitrone (PBN) against IRI-induced damage.
Main Methods:
- Utilized salicylate trapping of hydroxyl free radicals, spin-trapping, and protein oxidation quantitation.
- Assessed glutamine synthetase activity and susceptibility to peroxidation in brain homogenates.
- Compared IRI effects on lethality and energy production capacity in younger versus older gerbils.
Main Results:
- Confirmed oxidative events in the IRI-lesioned gerbil brain, correlating with decreased glutamine synthetase activity.
- IRI-lesioned brains showed increased susceptibility to peroxidation compared to controls.
- Older gerbils exhibited higher lethality and impaired energy production post-IRI than younger gerbils.
- The spin-trapping agent PBN demonstrated protective effects against IRI.
Conclusions:
- IRI induces oxidative damage in the brain, leading to loss of glutamine synthetase activity and potentially glutamate excitotoxicity.
- Age influences susceptibility to IRI, with older gerbils being more vulnerable.
- PBN offers protection against IRI, highlighting its potential as a neuroprotective agent.
- Energy production capacity and gene product synthesis are hypothesized to be crucial for IRI survival, with higher brain functions inversely related to oxidative damage.