AGE EFFECT ON BRAIN PH DURING ISCHEMIA/REPERFUSION AND PH INFLUENCE ON PEROXIDATION

Older gerbils are more sensitive to ischemia/reperfusion injury (IRI) than younger ones. Utilizing P-31-NMR to monitor in vivo pH and high energy phosphates of brain cortex undergoing an IRI showed that cortical intracellular pH decreased to 6.35 after ischemia and then increased with reperfusion, but older gerbils required significantly more time to recover than younger animals. Brain high energy phosphates dropped during ischemia but rebounded within 20 min reperfusion in younger gerbil brain but remained significantly lower in older gerbil brain far 50 min. These data suggest that IRI-induced brain acidification may enhance oxidative damage. In an in vitro system it was shown in both young and old brain homogenate that peroxidation rate increased when the pH of the incubation medium was decreased from 7.4 to 6.4. This was true in the presence or absence of an ADP/Fe/Ascorbate system in both young and old brain homogenate. Enhancement of peroxidation rate by ADP/Fe/Ascorbate addition was much more pronounced at pH 7.4 (30- to 40-fold increase) as compared to pH 6.4 (7.8- to 9.5-fold increase). This data can be interpreted to indicate that the lower pH makes endogenous Fe more available to catalyze oxidative damage. The fact that brain pH and high energy phosphates remain lower in older gerbil brains during IRI suggests that brain mitochondria from older animals are less capable of responding to a large oxidative stress brought on by an IRI. It is also possible that other processes leading to neuronal death are put into operation much faster in older gerbil brain and the delayed recovery of both pH and high energy phosphates in older gerbil brain reflects a substained damage and that age mediates an increased sensitivity to those processes.