Stroke occurs more frequently as age increases. We have shown that an ischemia/reperfusion insult (IRI) to brain of Mongolian gerbils causes lethality in old gerbils significantly more than in younger animals. We have shown using four separate approaches including two exogenous traps, salicylate and phenyl-t-butyl nitrone (PBN), as well as measurement of brain protein oxidation that oxidative damage does occur in the IRI-lesioned brain. In addition, the spin-trap, PBN, protected animals from brain injury from an lRI. Our preliminary data allow us to postulate that crucial oxidation-mediated lesions occur in the old gerbil brain which makes it less able to withstand the massive oxidative stress and disproportionate demand on energy production requirement brought on by an lRI. To test this hypothesis, we will use in vivo trapping of free radicals, using salicylate and the spin-trap PBN, as well as brain protein oxidation to determine if an IRI produces crucial oxidative damage in old gerbils as compared to younger animals. (31)P-NMR spectroscopy will be used to monitor the metabolic history of each treated gerbil. We will determine if the IRI induced spin trapped free radicals are different in old versus younger gerbils. Oxidative damage to gerbil brain DNA and RNA will be assessed by measuring the 8-hydroxyguanine content and particular attention will be directed toward synaptosomal DNA and RNA. Older gerbil brains peroxidize less than younger ones yet peroxidation impairs endogenous respiration in old brain synaptosomes but not those from younger animals. We will assess propensity of IRI-lesioned gerbil brain to peroxidize during the reperfusion phase to determine if brain from older animals show significantly different time-course patterns as compared to younger animals. All of the proposed studies should help explain why old animals are more susceptible to an IRI.
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