Oxidative stress plays a key role in the pathogenesis of age-related neurodegeneration, and the nonenzymatic production of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) may represent a reliable index of cellular oxidative damage. Garlic (Allium sativum) has been associated with peripheral antioxidant activities and therefore might prevent or reverse 8-iso-PGF(2alpha) production, but scant data are available on its possible neuroprotective effects. Therefore, we have studied the possible antioxidant effects of a garlic extract in rat brain synaptosomes obtained from young (3-month-old) and aged (14-month-old) male Wistar rats that were perfused, in vitro, with graded concentrations of a garlic extract (10-500 microg/mL). Release in the effluent was evaluated, both in the basal state and after hydrogen peroxide-induced oxidative stress. In young rats, we observed a concentration-dependent inhibitory effect of the garlic extract on brain 8-iso-PGF(2alpha) production, both basally and after hydrogen peroxide-induced oxidative stimulus. In aged rats, 8-iso-PGF(2alpha) production was not affected by the garlic extract in the basal state, whereas, after hydrogen peroxide-induced oxidative stimulus, an antioxidant effect of the garlic extract appeared only at the higher concentration tested. In conclusion, garlic supplementation could be effective in preventing brain oxidative damage in young animals, whereas the aging brain seems to be resistant to the antioxidant effects of garlic, in vitro.