INCREASING VULNERABILITY OF ASTROCYTES TO OXIDATIVE INJURY WITH AGE DESPITE CONSTANT ANTIOXIDANT DEFENSES

This paper investigates the vulnerability of astrocytes to oxidative i njury as a function of age in culture in mice. Primary murine cortical astrocyte cultures of different ages were exposed to H2O2, combined o xygen-glucose de-privation or glucose deprivation. Astrocytes became m ore vulnerable to damage from each injury paradigm with age, showing t ransitions between 15 and 22 days. Both the antioxidant glutathione an d superoxide dismutase activity increased after 30 days in culture, wh ile catalase activity did not change up to 34 days. When the decrease in glutathione with injury was measured, young cells showed no change with H2O2 and decreases of <20% after oxygen-glucose deprivation or gl ucose deprivation, while older cultures lost >50% of their glutathione with the same insults. Since iron can be a catalyst for hydroxyl radi cal formation, we stained cultures and Found both iron staining and fe rritin immunoreactivity increased with age. Increased iron correlated with protection by deferoxamine against H2O2 injury. The three injury paradigms each had a unique pattern of protection by antioxidants. Dim ethylthiourea, a hydrophilic antioxidant, protected from all three ins ults. Trolox, a lipophilic antioxidant, protected older astrocytes fro m oxygen-glucose deprivation and glucose deprivation. Deferoxamine pro vided near complete protection from H2O2, partial protection from oxyg en-glucose deprivation and no protection from glucose deprivation. As evidence of increasing oxidative stress, lipid peroxidation resulting from oxygen-glucose deprivation increased with age, assessed with cis- parinaric acid. The increasing sensitivity of ageing astrocytes to oxi dative injury occurs while antioxidant defenses are maintained. Increa sed sensitivity to H2O2 or oxygen-glucose deprivation correlates with iron accumulation. (C) 1997 IBRO.