Age influence on oxidative events during brain ischemia/reperfusion.
Brain readily undergoes oxidative damage if it is organizationally disrupted. Iron plays a catalytic role in mediating oxidative damage in brain homogenate. Utilizing several methods to assess oxidative events, including salicylate trapping of hydroxyl free radicals, spin-trapping of free radicals and quantitation of protein oxidation, we have clearly demonstrated that oxidative events do occur in the ischemia/ reperfusion lesioned Mongolian gerbil brain. In the gerbil model, ischemia/reperfusion insult (IRI) mediated protein oxidative damage is accompanied by a concomitant loss of glutamine synthetase activity. The loss of glutamine synthetase activity may possibly lead to the build-up of glutamate, an excitotoxic amino acid which has been strongly implicated in the neuronal death observed in hippocampus following an IRI. The brain homogenate from an IRI-lesioned animal is more susceptible to peroxidation than comparable sham-operated control animals. We have discovered that an IRI causes lethality in older gerbils more readily than in younger gerbils. We have also found that the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) protects gerbils from an IRI. Data are presented which implicate that an IRI may seriously impair the energy production capacity of older gerbils more than comparable oxidative stresses in younger animals. We hypothesize that energy production capacity and its utilization for the synthesis of new gene products may be key events which help mediate survival from an IRI. In addition we hypothesize that higher brain functions, including memory and learning are inversely correlated with oxidative damage in the brain. The elucidation of the mechanisms involved in this fascinating area of research and the design of new protective agents to prevent oxidative damage in brain is a most exciting challenge.
Floyd
R A
RA
Molecular Toxicology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, U.S.A.
Carney
J M
JM